Espen Andre Haavardsholm

• Østergaard, Mikkel; Haavardsholm, Espen Andre; Nowak, Miroslawa; Luo, Yi; Landis, Jessica & Fura, Aberra [Show all 14 contributors for this article] (2026). Efficacy and safety of branebrutinib (BMS-986195), an irreversible Bruton's tyrosine kinase inhibitor, for the treatment of rheumatoid arthritis: a phase 2a, randomised, double-blind, placebo-controlled study. The Lancet Rheumatology. 8(7), p. e539–e549. doi: 10.1016/S2665-9913(25)00374-1. Full text in Research Archive
• Smolen, Josef S.; Edwards, Christopher J.; Konzett, Victoria; Laskou, Faidra; Aletaha, Daniel & Caporali, Roberto [Show all 50 contributors for this article] (2026). EULAR recommendations for the management of rheumatoid arthritis with synthetic and biologic disease-modifying antirheumatic drugs: 2025 update. Annals of the Rheumatic Diseases. ISSN 0003-4967. doi: 10.1016/j.ard.2026.01.023. Full text in Research Archive
• Lampa, Jon; Nordström, Dan; Vollenhoven, Ronald van; Hetland, Merete Lund; Haavardsholm, Espen A. & Østergaard, Mikkel [Show all 71 contributors for this article] (2026). Certolizumab pegol, abatacept, tocilizumab or active conventional therapy in early rheumatoid arthritis: 48-week patient-reported outcomes from the NORD-STAR trial. The Lancet Rheumatology. 8(4), p. e285–e294. doi: 10.1016/s2665-9913(26)00007-x. Full text in Research Archive Show summary

  Background Pain, fatigue, and impaired health-related quality of life are common manifestations of rheumatoid arthritis. The aim of this study was to compare the effects of active conventional treatment with three different biological disease-modifying antirheumatic drugs (DMARDs) on patient-reported outcomes after 48 weeks, in patients with early rheumatoid arthritis using data from the NORD-STAR trial. Methods NORD-STAR was an investigator-initiated open-label randomised controlled trial done at 29 rheumatology centres across Denmark, Finland, Iceland, Norway, Sweden, and the Netherlands. Newly diagnosed patients aged 18 years or older, with rheumatoid arthritis (according to the 2010 American College of Rheumatology–European Allience of Associations for Rheumatology classification criteria for rheumatoid arthritis), symptom duration less than 24 months and who were naïve to DMARDs were randomly assigned (1:1:1:1) to receive active conventional treatment, certolizumab pegol, abatacept, or tocilizumab. The patient-reported outcomes assessed at baseline and weeks 4, 8, 12, 16, 24, 32, 40, and 48 included pain, patient's global assessment of disease activity, Health Assessment Questionnaire Disability Index, Fatigue, Short Form-36 (reflecting health-related quality of life, morning stiffness, and patient's acceptable symptom state). Linear mixed regression and logistic regression analyses were adjusted for sex, country, baseline patient-reported outcomes values, anti-citrullinated protein antibody status, and treatment group. Proportions of patients reporting improvements greater than or equal to the minimal clinically important difference (MCID) were assessed. There was lived experience involvement in the design and implementation of the study. This trial was registered with ClinicalTrials.gov, NCT01491815, and EudraCT, 2011-004720-35. Findings Between Dec 14, 2012, and Dec 11, 2018, 812 patients were enrolled and randomly assigned; after exclusion of 17 patients not receiving tocilizumab due to administrative issues, the intention-to-treat population consisted of 795 patients (200 [25%] received active conventional treatment, 203 [26%] received certolizumab pegol plus methotrexate, 204 [26%] received abatacept plus methotrexate, and 188 [24%] received tocilizumab plus methotrexate). 547 (69%) of 795 patients were female, 248 (31%) were male, the mean age was 54 years (SD 15). Between baseline and week 48 large and clinically relevant improvements in patient-reported outcomes were observed in all treatment groups. At 48 weeks the biological DMARD groups had larger improvements in pain, fatigue, physical component score, and bodily pain of SF-36 compared with the active conventional treatment group. For pain, improvement exceeding MCID was reported by 155 (76%) of 203 patients with certolizumab pegol plus methotrexate and 162 (79%) of 204 patients with abatacept plus methotrexate compared with 136 (68%) of 200 patients in the active conventional treatment group. In the group of patients with tocilizumab and methotrexate 132 (70%) of 188 patients reported pain improvement exceeding MCID. The absolute differences between the biological DMARD groups and the active conventional treatment group were otherwise generally marginal. Interpretation All treatment groups showed substantial improvements in patient-reported outcomes over time. Biological DMARDs produced somewhat greater gains in pain, fatigue, and physical quality of life measures than conventional treatments, though overall differences between groups were small. The results highlight that early treatment and effective disease control in rheumatoid arthritis lead to strong patient-reported benefits regardless of therapy type. Funding Stockholm County Council, Swedish Medical Research Council, Swedish Rheumatism Association, Academy of Finland, Finska Läkaresällskapet, South-Eastern Health Region Norway, HUS Institutional grant, Icelandic Society for Rheumatology, Interregional grant from all health regions in Norway, NordForsk, Regionernes Medicinpulje, The Research Fund of University Hospital Reykjavik, UCB, Bristol Myers Squibb.

• Anderle, Karolina; Sieghart, Daniela; Durechova, Martina; Bonnay, François; Kerschbaumer, Andreas & Chatzidionysiou, Katerina [Show all 19 contributors for this article] (2026). An international, multicentre, interventional, randomised, assessor-blinded trial to MAXimise the METHotrexate therapy potential in patients with active rheumatoid arthritis (MethMax trial): study protocol for a randomised controlled trial. Trials. 27. doi: 10.1186/s13063-026-09519-4. Full text in Research Archive Show summary

  Background Methotrexate (MTX) is recommended as first-line therapy in patients with rheumatoid arthritis (RA), proven to be effective, safe and inexpensive. However, a significant proportion of patients does not achieve disease remission with MTX monotherapy. Main reasons include insufficient dose up-titration to the maximal recommended oral dose or the delayed switch to a subcutaneous administration route. We hypothesise, that by dose and route optimisation, a higher proportion of patients can achieve remission. Further, exploratory biomarkers will give new insights on individual MTX metabolism and drug adherence. Methods The MethMax trial is a prospective, randomised, assessor-blinded, parallel-group, superiority, low-intervention trial, including 182 patients across 7 European countries. Patients with active RA, naïve to biologic (except tumour necrosis factor alpha inhibitors; TNFi) or targeted synthetic antirheumatic drugs, who have been on a stable oral MTX therapy for the past 3 months are randomised in a 1:1 ratio to 25 mg MTX weekly, either administered orally or subcutaneously. Additionally, both arms receive a short-term glucocorticoid regimen with a four-week tapering and withdrawal protocol. The primary endpoint is the difference in proportion of patients achieving remission defined as the Clinical Disease Activity Index (CDAI) ≤ 2.8 at week 24, comparing the dose/route optimisation and oral dose optimisation. The active study duration for each patient is 24 weeks. Study visits take place at baseline, weeks 4, 12, 16 and 24. Clinical efficacy and safety parameters are obtained at each visit. Patient-reported outcomes, exploratory biomarkers as well as medication adherence are assessed. Written consent is obtained for all participants. The study has received regulatory approval via the Clinical Trials Information System and Medicines and Healthcare products Regulatory Agency and has included the first patient in August 2024. Discussion The anticipated results will provide insights whether the subcutaneous administration of 25 mg MTX is advantageous in achieving CDAI remission when compared to the oral intake after 24 weeks and inform the community regarding the utility of established and newly developed biomarkers, as well as the potential impact of inadequate drug adherence. The MethMax study is aimed to optimise individual therapy in RA and provide more precise pharmacological MTX management recommendations.

• Uhlig, Tillmann; Karoliussen, Lars Fridtjof; Sexton, Joseph; Haavardsholm, Espen Andre; Provan, Sella Aarrestad & Solomon, D. H. [Show all 7 contributors for this article] (2026). Duration and dose of allopurinol needed to attain the serum urate target in gout. Scandinavian Journal of Rheumatology. ISSN 0300-9742. doi: 10.1080/03009742.2026.2648357. Full text in Research Archive Show summary

  Objective: To examine, in patients with gout using escalating urate-lowering therapy (ULT), the treatment durationand allopurinol dose required to attain the serum urate (SU) target (< 360 μmol/L; < 6 mg/dL). Method: We studied patients in the NOR-Gout prospective cohort with a recent gout flare and increased SU(> 360 μmol/L). Patients escalated allopurinol dosage until reaching the SU treatment target of <360 µmol/L,switching, if needed, to febuxostat. Results: Of 211 patients, 95.2% were male; mean ± sd age was 56.7 ± 13.7 years, disease duration 8.1 years, 16.6%had clinical tophi, and 12.8% used allopurinol at cohort entry. Mean SU (μmol/L) was reduced from 500 at baseline to312 at 1 year and 325 at 2 years. Target SU was attained at least once during year 1 by 197 patients (93.4%). Mediantime to attaining the treatment target was 2 months (mean 2.9 months), and median allopurinol dose was 200 mg(mean 243 mg). Eighty per cent of patients reached the treatment target by 3 months. Patients with SU >480 μmol/L atbaseline needed a median of 3 months to attain target SU versus 2 months for patients with SU <480 μmol/L (log-rankp < 0.001). A switch to febuxostat was seen in 12.4% at year 1 and 15.1% at year 2. Conclusion: Treat-to-target ULT using allopurinol leads to attainment of the SU target within 2–3 months at lowdoses for most patients. Very few patients did not achieve the treatment target at least once during year 1. Trial registration: ACTRN12618001372279

• Nagafuchi, Yasuo; Maarseveen, Tjardo D.; Lend, Kristina; Rudin, Anna; Gudbjornsson, Bjorn & Nordström, Dan [Show all 21 contributors for this article] (2026). Hand-dominant joint involvement pattern associates with favourable, and polyarthritis with unfavourable, treatment response to both csDMARDs and bDMARDs in early rheumatoid arthritis: a combined analysis of NORD-STAR and BeSt trials. Annals of the Rheumatic Diseases. ISSN 0003-4967. doi: 10.1016/j.ard.2026.02.005. Full text in Research Archive
• Lend, Kristina; Twisk, Jos W.R.; Koopman, Frieda A.; Rudin, Anna; Hetland, Merete Lund & Uhlig, Tillmann [Show all 17 contributors for this article] (2026). Flare risk after oral glucocorticoid bridging with methotrexate or intra-articular bridging with triple therapy in early rheumatoid arthritis. Journal of Internal Medicine. ISSN 0954-6820. doi: 10.1111/joim.70094. Full text in Research Archive
• Gehin, Johanna; Klaasen, Rolf; Kristianslund, Eirik; Jyssum, Ingrid; Sexton, Joseph & Warren, David John [Show all 11 contributors for this article] (2026). The Effect of Certolizumab Pegol Dose and Dose Changes on Plasma Trough Levels: Data From a Randomized Phase III Trial. Therapeutic Drug Monitoring. ISSN 0163-4356. doi: 10.1097/FTD.0000000000001440. Full text in Research Archive
• Brinkmann, Gina Charlotte Hetland; Sundlisæter, Nina Paulshus; Nordberg, Lena Kristine Bugge; Sexton, Joseph; Ikdahl, Eirik & Aga, Anna-Birgitte [Show all 10 contributors for this article] (2026). Successful discontinuation of oral glucocorticoids after short-term bridging therapy in patients with newly diagnosed rheumatoid arthritis. Annals of the Rheumatic Diseases. ISSN 0003-4967. doi: 10.1016/j.ard.2026.01.003. Full text in Research Archive
• Holly, Teresa; Brun, Marthe Kirkesæther; Jørgensen, Kristin Kaasen; Goll, Guro Løvik; Sexton, Joseph & Gehin, Johanna [Show all 15 contributors for this article] (2026). Cost-effectiveness of proactive therapeutic drug monitoring of maintenance infliximab treatment in patients with immune-mediated inflammatory diseases: results from a randomised controlled trial. RMD Open. 12(1), p. 11–11. doi: 10.1136/rmdopen-2025-006329. Full text in Research Archive
• Yoshida, Yusuke; Hammer, Hilde Berner; Sexton, Joseph; Nordberg, Lena Kristine Bugge; Aga, Anna-Birgitte & Terslev, Lene [Show all 8 contributors for this article] (2025). How to score the wrist joint by ultrasound: exploration of the most sensitive joint assessment during follow-up of early or established rheumatoid arthritis. Arthritis Research & Therapy. ISSN 1478-6354. 27(1). doi: 10.1186/s13075-025-03668-8. Full text in Research Archive
• Hammer, Hilde Berner; Karoliussen, Lars Fridtjof; Terslev, Lene; Haavardsholm, Espen A. & Uhlig, Till (2025). Ultrasound-detected crystal depositions and clinical flares dissolve during successful urate-lowering therapy: 5-year follow-up results from the treat-to-target NOR-Gout study. Annals of the Rheumatic Diseases. ISSN 0003-4967. doi: 10.1016/j.ard.2025.10.029. Full text in Research Archive
• Riskedal, Espen; Jugessur, Astanand; Syversen, Silje Watterdal; Hadley, Cathrine Lund; Harris, Jennifer Ruth & Mjaavatten, Maria Dahl [Show all 16 contributors for this article] (2025). A DNA methylation-based algorithm for diagnosing rheumatoid arthritis. Arthritis Research & Therapy. ISSN 1478-6354. 27. doi: 10.1186/s13075-025-03649-x. Full text in Research Archive Show summary

  Background Rheumatoid arthritis (RA), particularly seronegative disease, is difficult to diagnose early, which can delay treatment initiation. This study aims to develop a binary DNA methylation (DNAm)-based algorithm to diagnose RA. Methods Three datasets (discovery, training, holdout) were constructed from DNAm profiles from 1366 persons (treatment-naïve RA, other inflammatory/autoimmune diseases, healthy individuals). DNAm features that differentiate RA from other inflammatory/autoimmune diseases and healthy individuals were identified using the discovery set. Our classification algorithm was developed using machine learning techniques in the training set. Its diagnostic performance, with and without serological status, was evaluated in the holdout set containing RA cases (15 seropositive, 6 seronegative) and controls (14 other arthritides, 11 healthy individuals). Results Our algorithm included 391 DNAm features. Combined with serological status, it classified RA from controls in the holdout set with the following performance: sensitivity 0.90 [95% CI: 0.70–0.99], specificity 0.88 [95% CI: 0.69–0.97], and AUC 0.96 [95% CI: 0.91–1.00]. Its performance in classifying patients with seronegative RA versus those with other arthritides was: sensitivity 0.83 [95% CI: 0.36–1.00], specificity 0.79 [95% CI: 0.49–0.95], and AUC 0.81 [95% CI: 0.61–1.00]. Conclusions The present DNAm-based classification algorithm may be clinically useful for the early diagnosis of RA, especially in seronegative patients, which currently often poses a diagnostic challenge.

• Vasileiadis, Georgios K.; Zhang, Yuan; Laudette, Marion; Fatima, Tahzeeb; Ekwall, Anna-Karin Hultgård & Sureshkumar, Reshmi [Show all 23 contributors for this article] (2025). Acylcarnitine enrichment as a characteristic of rheumatoid arthritis fibroblast-like synoviocyte metabolic fingerprint. Journal of Translational Autoimmunity. 11, p. 100310–100310. doi: 10.1016/j.jtauto.2025.100310. Full text in Research Archive
• Fatima, Tahzeeb; Zhang, Yuan; Vasileiadis, Georgios K.; Rawshani, Araz; Vollenhoven, Ronald van & Lampa, Jon [Show all 20 contributors for this article] (2025). Disease activity and treatment response in early rheumatoid arthritis: an exploratory metabolomic profiling in the NORD-STAR cohort. Arthritis Research & Therapy. ISSN 1478-6354. 27(1). doi: 10.1186/s13075-025-03616-6. Full text in Research Archive Show summary

  Abstract Background The variability in treatment response in people with rheumatoid arthritis (RA) warrants the prediction of patients at high risk of treatment failure. Identification of biomarkers linked to clinical remission in RA is currently a challenge. Metabolomics may help to identify such biomarkers as it allows for a comprehensive exploration of disease-related variations that extends beyond the genome and proteome. This hypothesis-free exploratory metabolomics study aimed to profile serum metabolic alterations in early RA to understand the metabolic changes associated with disease activity and therapeutic response. Methods The study included 220 early RA participants from the NORD-STAR study, randomized at baseline into four arms, ranging from conventional anti-rheumatic treatment to biological drugs: methotrexate combined with prednisolone (1), certolizumab (2), abatacept (3), or tocilizumab (4). Untargeted metabolomics was performed in serum samples at baseline and 24-week follow-up. Participants achieving clinical disease activity index remission at 24 weeks were defined as responders. Machine learning models for treatment response were constructed using random forest, logistic regression, support vector machine and extreme gradient boosting algorithms based on selected features. Results We identified 278 metabolites, of which 39 were associated with baseline disease activity, including several acylcarnitines and amino acids. We also found 17 baseline metabolites associated with remission at 24 weeks in the overall cohort, including malic acid (β=-0.4), cytidine (β = 0.4), arginine (β = 0.3), and citrulline (β = 0.2), as well as specific metabolites and metabolic pathways associated with remission in the four treatment arms. Fifteen features were identified using machine learning-based multivariable selection. The best predictive model using logistic regression achieved AUC of 0.75 in training and 0.73 in the test set. Conclusions Our study has identified several baseline metabolites and metabolic pathways associated with disease activity and response to different treatments in early RA. By integrating metabolomics and clinical data, we developed predictive models for response to treatment in early RA, though their predictive performance remains limited.

• Alm, Linda Mathsson; Westerlind, Helga; Gehring, Isabel; Hansson, Monika; Ghasemzadeh, Nasim & Rojas-Restrepo, Jessica [Show all 17 contributors for this article] (2025). Recognition of Glycine Versus Nonglycine Citrulline Motifs Dictating the HLA Class II Association of Anticitrullinated Protein Antibodies: Insights From Autoantibody Profiling of 6,900 Scandinavian Patients With Rheumatoid Arthritis. Arthritis & Rheumatology. ISSN 2326-5191. doi: 10.1002/art.43161. Full text in Research Archive Show summary

  Objective. Rheumatoid arthritis (RA)–associated anticitrullinated protein antibodies (ACPAs) target various anti-gens by binding short citrulline amino acid motifs, resulting in heterogeneous ACPA profiles among patients. Herewe analyzed ACPA patterns by recognized citrulline motifs in relation to the RA risk factors HLA-DRB1 shared epitope(SE) alleles and history of smoking.Methods. Rheumatoid factor (RF) and anticyclic citrullinated peptide (CCP2) isotypes, 15 anti-Cit- and four anti-Carb/Acet-peptide-IgG, were centrally measured in 6,907 patients from five Scandinavian RA cohorts using fluoroen-zyme immunoassay and a custom-made multiplex solid-phase microarray. HLA-DRB1 SE alleles were imputed fromsingle-nucleotide polymorphism genotyping data.Results. Single-citrulline peptides derived from four multicitrulline peptides (Cit Fibα36-50 , Cit Fibβ60-74, Cit TNC5,and Cit Vim60-75) showed differential binding patterns, supporting recognition of citrulline motifs rather than long peptides.Four citrulline peptides (Cit Fibβ36-52, Cit Fibβ60-74-Cit3, Cit Fil307-324, and Cit Vim60-75-Cit1) captured 97% of IgG anti-CCP2+ patients. Patient subsets based on ACPA, anti-Carb/Acet, and RF displayed differences in ACPA compositionand disease activity but not comorbidities. Different ACPAs overlapped, but when dichotomizing patients based on highreactivity to peptide citrulline motifs, only ACPA to nonglycine citrulline motif associated with HLA SE alleles. In IgG anti-CCP2+ patients, 90% of those with only high nonglycine ACPA were HLA SE allele carriers compared with 67% in thegroup with glycine motif–only ACPA (odds ratio 4.5). Smoking status associated with IgA and glycine motif ACPA.Conclusion. Although citrulline-glycine motifs are prevalent ACPA targets, our data reveal that HLA SE alleles areprimarily associated with ACPA to nonglycine citrulline motifs, providing insight in ACPA T cell dependance. Yet, theetiologic significance of ACPA targeting different protein structures remains unknown.

• Berg, Inger Jorid; Kristianslund, Eirik; Tveter, Anne Therese; Sexton, Joseph; Bakland, Gunnstein & Gossec, Laure [Show all 15 contributors for this article] (2025). Remote monitoring or patient-initiated care in axial spondyloarthritis: a 3-armed randomised controlled noninferiority trial. Annals of the Rheumatic Diseases. ISSN 0003-4967. doi: 10.1016/j.ard.2025.04.019. Full text in Research Archive
• Hetland, Merete Lund; Heiberg, Marte Schrumpf; Sokka-Isler, Tuulikki; Rudin, Anna; Østergaard, Mikkel & Haavardsholm, Espen A. [Show all 21 contributors for this article] (2025). Treatment with methotrexate plus oral prednisolone versus triple therapy (methotrexate/sulfasalazine/hydroxychloroquine) plus intra-articular glucocorticoids in early rheumatoid arthritis: a prespecified nonrandomised subgroup analysis of clinical and radiographic data at 48 weeks from the NORD-STAR trial's conventional treatment arm. Annals of the Rheumatic Diseases. ISSN 0003-4967. 84, p. 937–948. doi: 10.1016/j.ard.2025.03.002. Full text in Research Archive Show summary

  Objectives In the NOrdic Rheumatic Diseases Strategy Trials And Registries (NORD-STAR) trial, the active conventional arm had 2 nonrandomised regimens: arm 1A (oral group; Sweden, Norway, Netherlands, and Iceland) and arm 1B (injection group; Denmark and Finland). We report clinical, patient-reported, safety, and radiographic outcomes after 48 weeks. Methods Oral group received methotrexate plus oral prednisolone (20.0 mg/d, tapered rapidly, discontinued week 36); Injection group received triple therapy (methotrexate, sulphasalazine, hydroxychloroquine) and mandatory intra-articular glucocorticoid injections. The primary end point was analysed by logistic regression with several approaches for handling missing outcomes. Results In total, 137 and 80 patients were included in the oral group and injection group; 78% vs. 89% completed, respectively. At 48 weeks, adjusted clinical disease activity index remission ≤2.8 rates (95% CI) were 36% (28-44) and 55% (42-68), respectively; the risk difference (primary outcome) was 19% (2-35). Similarly, key secondary clinical, patient-reported and safety outcomes showed numerically better results in the injection group vs oral group, for example, infections occurred in 53% vs 30%, respectively. Radiographic progression (Δtotal van der Heijde-modified Sharp Score) was low: oral group: adjusted mean, 0.26 (95% CI, 0.08-0.43); injection group: adjustedd mean, 0.80 (95% CI, 0.55-1.05). Cumulative dose of oral/intra-articular glucocorticoids (median) was 1905 mg prednisolone for the oral group and 165 mg for the injection group. Conclusions In treatment-naïve patients with early rheumatoid arthritis, triple therapy and mandatory glucocorticoid joint injections had numerically better clinical outcomes, fewer withdrawals, fewer adverse events, and lower cumulative dose of glucocorticoids, but slightly worse radiographic outcomes than treatment with methotrexate and oral prednisolone. These findings, although nonrandomised, suggest a potential for optimising treatment strategy with conventional therapies in early rheumatoid arthritis.

• Lorentsen, Jing Lisa Li; Brunborg, Cathrine; Aasebø, Anders Theodor Michaelsen; Valeur, Jørgen; Haavardsholm, Espen A. & Molberg, Øyvind [Show all 8 contributors for this article] (2025). Incidence and prevalence of Behçet's disease in Oslo, Norway: a two-decade population-based analysis. Rheumatology. ISSN 1462-0324. 64(8), p. 4703–4712. doi: 10.1093/rheumatology/keaf224. Full text in Research Archive
• Uhlig, Till; Stjärne, Johan Folke Håkan; Karoliussen, Lars Fridtjof; Sexton, Joseph; Eskild, Tron Hovind & Provan, Sella Aarrestad [Show all 8 contributors for this article] (2025). Remission in gout is possible: 5-year follow-up in the NOR-Gout study. Seminars in Arthritis & Rheumatism. ISSN 0049-0172. 72. doi: 10.1016/j.semarthrit.2025.152698. Full text in Research Archive
• Kjørholt, Kaja Eriksrud; Sundlisæter, Nina Paulshus; Aga, Anna-Birgitte; Sexton, Joseph; Olsen, Inge Christoffer & Lexberg, Åse S. [Show all 21 contributors for this article] (2025). Three-Year Results of Tapering Tumor Necrosis Factor Inhibitor to Withdrawal Compared to Stable Tumor Necrosis Factor Inhibitor Among Patients With Rheumatoid Arthritis in Sustained Remission: A Multicenter Randomized Trial. Arthritis & Rheumatology. ISSN 2326-5191. 77(10), p. 1327–1336. doi: 10.1002/art.43199. Full text in Research Archive Show summary

  Objective Tapering of tumor necrosis factor inhibitor (TNFi) treatment in rheumatoid arthritis (RA) remission is debated. We assessed the effect of tapering TNFi to withdrawal versus continued stable TNFi on flare-free survival and joint damage progression over three years. Methods ARCTIC REWIND was a multicenter open-label, noninferiority trial that included patients with RA in remission for ≥12 months taking stable TNFi therapy. Patients were randomized 1:1 to taper TNFi to withdrawal or continue stable treatment. The primary end points of the current study were flare-free survival and radiographic progression over three years. Flare-free survival was analyzed by Kaplan-Meier methods, flare rates were analyzed by Cox regression, and radiographic progression was analyzed by logistic mixed-effects models. Results of 99 randomized patients, 92 received the allocated therapy, and 80 completed the three-year follow-up. The mean baseline Disease Activity Score based on the 44 joint count was 0.8, and conventional synthetic disease-modifying antirheumatic drug comedication was used by 90% of patients. After three years, 25% (95% confidence interval [CI] 13%–38%) remained flare free in the tapering TNFi group, compared to 85% (95% CI 70%–93%) in the stable group, and the corresponding hazard ratio for flare was 9.4 (95% CI 3.9–22.8, P < 0.0001). In the tapering group, 6 of 41 (15%) experienced radiographic progression, compared with 3 of 38 (8%) in the stable group (risk difference 6.7%, 95% CI −7.1% to 20.5%, P = 0.3). Adverse events occurred in 81% of the patients in the tapering group and 89% of the patients in the stable group. Conclusion In contrast to those receiving stable TNFi treatment, a minority of patients with RA in remission tapering TNFi to withdrawal remained flare free over three years. There was no statistically significant difference in radiographic progression between the groups.

• Li, Gaoyang; Kolan, Shrikant; Grimolizzi, Franco; Sexton, Joseph; Malachin, Giulia & Goll, Guro Løvik [Show all 12 contributors for this article] (2025). Development of machine learning models for predicting non-remission in early RA highlights the robust predictive importance of the RAID score-evidence from the ARCTIC study. Frontiers of Medicine. ISSN 2095-0217. 12. doi: 10.3389/fmed.2025.1526708. Full text in Research Archive Show summary

  Introduction: Achieving remission is a critical therapeutic goal in the management of rheumatoid arthritis (RA). Despite methotrexate being the cornerstone of early RA treatment, a significant proportion of patients fail to achieve remission. This study aims to predict 6-month non-remission in 222 disease-modifying antirheumatic drug (DMARD)-naïve RA patients initiating methotrexate monotherapy, using baseline patient characteristics from the ARCTIC trial. Methods: Machine learning models were developed utilizing twenty-one baseline demographic, clinical and laboratory features to predict non-remission according to ACR/EULAR Boolean, SDAI and CDAI criteria. The model employed a super learner algorithm that combine three base algorithms of elastic net, random forest and support vector machine. The model performance was evaluated through five independent unseen tests with nested 5-fold cross-validation. The predictive power of each feature was assessed using a composite measure derived from individual algorithm estimates. Results: The model demonstrated a mean AUC-ROC of 0.75-0.76, with mean sensitivity of 0.77-0.81, precision (also referred to as Positive Predictive Value) of 0.77-0.79 and specificity of 0.63-0.66 across the criteria. Predictive power analysis of each feature identified the baseline Rheumatoid Arthritis Impact of Disease (RAID) score as the strongest predictor of non-remission. A simplified model using RAID score alone demonstrated comparable performance to the full-feature model. Conclusion: These findings highlight the potential utility of baseline RAID scorebased model as an effective tool for early identification of patients at risk of nonremission in clinical practise.

• Brun, Marthe Kirkesæther; Gehin, Johanna; Hammersbøen, Kristin Reine; Warren, David; Klaasen, Rolf & Sexton, Joseph [Show all 15 contributors for this article] (2024). Clinical consequences of infliximab immunogenicity and the effect of proactive therapeutic drug monitoring: exploratory analyses of the randomised, controlled NOR-DRUM trials. The Lancet Rheumatology. 6(4), p. e226–e236. doi: 10.1016/S2665-9913(23)00341-7. Full text in Research Archive
• Wolf, Asia-Sophia Fumika Michaela; Hammersbøen, Kristin Reine; Ørbo, Hilde Sofie Sager; Bhandari, Sabin; Solum, Guri & Kjønstad, Ingrid Fadum [Show all 30 contributors for this article] (2024). T cell responses to repeated SARS-CoV-2 vaccination and breakthrough infections in patients on TNF inhibitor treatment: a prospective cohort study. EBioMedicine. 108. doi: 10.1016/j.ebiom.2024.105317. Full text in Research Archive Show summary

  Background Understanding cellular responses to SARS-CoV-2 immunisations is important for informing vaccine recommendations in patients with inflammatory bowel disease (IBD) and other vulnerable patients on immunosuppressive therapies. This study investigated the magnitude and quality of T cell responses after multiple SARS-CoV-2 vaccine doses and COVID-19 breakthrough infection. Methods This prospective, observational study included patients with IBD and arthritis on tumour necrosis factor inhibitors (TNFi) receiving up to four SARS-CoV-2 vaccine doses. T cell responses to SARS-CoV-2 peptides were measured by flow cytometry before and 2–4 weeks after vaccinations and breakthrough infection to assess the frequency and polyfunctionality of responding cells, along with receptor-binding domain (anti-RBD) antibodies. Findings Between March 2, 2021, and December 20, 2022, 143 patients (118 IBD, 25 arthritis) and 73 healthy controls were included. In patients with either IBD or arthritis, humoral immunity was attenuated compared to healthy controls (median anti-RBD levels 3391 vs. 6280 BAU/ml, p = 0.008) after three SARS-CoV-2 vaccine doses. Patients with IBD had comparable quantities (median CD4 0.11% vs. 0.11%, p = 0.26, CD8 0.031% vs. 0.047%, p = 0.33) and quality (polyfunctionality score: 0.403 vs. 0.371, p = 0.39; 0.105 vs. 0.101, p = 0.87) of spike-specific T cells to healthy controls. Patients with arthritis had lower frequencies but comparable quality of responding T cells to controls. Breakthrough infection increased spike-specific CD8 T cell quality and T cell responses against non-spike peptides. Interpretation Patients with IBD on TNFi have T cell responses comparable to healthy controls despite attenuated humoral responses following three vaccine doses. Repeated vaccination and breakthrough infection increased the quality of T cell responses. Our study adds evidence that, in the absence of other risk factors, this group may in future be able to follow the general recommendations for COVID-19 vaccines.

• Kared, Hassen; Jyssum, Ingrid; Alirezaylavasani, Amin; Egner, Ingrid Marie; Tran, Trung & Tietze, Lisa [Show all 17 contributors for this article] (2024). Dynamics of SARS-CoV-2 immunity after vaccination and breakthrough infection in rituximab-treated rheumatoid arthritis patients: a prospective cohort study. Frontiers in Immunology. 15:1296273, p. 1–12. doi: 10.3389/fimmu.2024.1296273. Full text in Research Archive Show summary

  Background: SARS-CoV-2 vaccination in rheumatoid arthritis (RA) patients treated with B cell-depleting drugs induced limited seroconversion but robust cellular response. We aimed to document specific T and B cell immunity in response to vaccine booster doses and breakthrough infection (BTI). Methods: We included 76 RA patients treated with rituximab who received up to four SARS-CoV-2 vaccine doses or three doses plus BTI, in addition to vaccinated healthy donors (HD) and control patients treated with tumor necrosis factor inhibitor (TNFi). We quantified anti-SARS-CoV-2 receptor-binding domain (RBD) Spike IgG, anti-nucleocapsid (NC) IgG, 92 circulating inflammatory proteins, Spike-binding B cells, and Spike-specific T cells along with comprehensive high-dimensional phenotyping and functional assays. Findings: The time since the last rituximab infusion, persistent inflammation, and age were associated with the anti-SARS-CoV-2 RBD IgG seroconversion. The vaccine-elicited serological response was accompanied by an incomplete induction of peripheral Spike-specific memory B cells but occurred independently of T cell responses. Vaccine- and BTI-elicited cellular immunity was similar between RA and HD ex vivo in terms of frequency or phenotype of Spike-specific cytotoxic T cells and in vitro in terms of the functionality and differentiation profile of Spike-specific T cells. Interpretation: SARS-CoV-2 vaccination in RA can induce persistent effector T-cell responses that are reactivated by BTI. Paused rituximab medication allowed serological responses after a booster dose (D4), especially in RA with lower inflammation, enabling efficient humoral and cellular immunity after BTI, and contributed overall to the development of potential durable immunity.

• Ferreira, Ricardo J O; Henriques, Adriana; Moe, Rikke Helene; Matos, Cristiano; Tveter, Anne Therese & Østerås, Nina [Show all 11 contributors for this article] (2024). Presentation of the first international research network to foster high-quality clinical trials testing non-pharmacological interventions (TRACTION network). BMJ Open. 14(7). doi: 10.1136/bmjopen-2023-081864. Full text in Research Archive Show summary

  Clinical trials are essential for evaluating the efficacy and safety of new treatments and health interventions. However, while pharmacological trials are well-established, non-pharmacological trials face unique challenges related to their complexity and difficulties such as recruitment, retention, intervention standardisation, selection of outcome measures and blinding of clinicians, participants and data collectors. This communication paper describes the objectives, implementation steps and bylaws of the ‘Trials foR heAlth Care inTerventIONs’ Network (TRACTION), established by an international multiprofessional task force of experts to foster high-quality non-pharmacological research, ultimately improving patient care and healthcare outcomes. The TRACTION research network will provide information and resources through a collaborative hub for researchers, health professionals, patient research partners and stakeholders in diverse biomedical and healthcare areas, connecting people with different levels of expertise but with the same interests (eg, to evaluate the effect of non-pharmacological interventions, recruiting participants). This open network will support researchers in optimising trial design, participant recruitment, data management and analysis, and disseminating and implementing trial results. The network will also facilitate specialisation training and provide educational materials and mentoring.

• Holten, Karen; Sundlisæter, Nina Paulshus; Sexton, Joseph; Kjørholt, Kaja Eriksrud; Nordberg, Lena Bugge & Uhlig, Tillmann [Show all 11 contributors for this article] (2024). Agreement between patient-reported flares and clinically significant flare status in patients with rheumatoid arthritis in sustained remission: data from the ARCTIC REWIND trials. RMD Open. 10(3). doi: 10.1136/rmdopen-2024-004444. Full text in Research Archive Show summary

  Objectives To explore the agreement between patient-reported flare status and clinically significant flare status in patients with rheumatoid arthritis (RA) in sustained remission. Method Patients with RA in remission for ≥12 months on stable treatment were included in the ARCTIC REWIND tapering trials and pooled 12-month data used in current analyses. Patient-reported flare status was assessed according to the Outcome Measures in Rheumatology flare questionnaire; ‘Are you having a flare of your RA at this time?’ (yes/no). A clinically significant flare was defined as a combination of Disease Activity Score (DAS) >1.6, increase in DAS of ≥0.6 and 2 swollen joints, or the rheumatologist and patient agreed that a clinically significant flare had occurred. Agreement coefficient, sensitivity, specificity and predictive values of patient-reported flare status with regard to clinically significant flare status were determined. Results Of 248 patients, 64% were women, age 56.1 (11.8) years, disease duration 4.1 (2.8–7.4) years, DAS 0.8 (0.3). 35% of patients reported a flare at least once, clinically significant flares were recorded in 21%. 48/53 clinically significant flares (91%) led to an intensification of disease-modifying antirheumatic drugss. In 621/682 (91%) visits, patient-reported and clinically significant flare status were in agreement, agreement coefficient 0.89. Sensitivity and specificity were both 91%, positive predictive value of patient-reported flare status 46% and negative predictive value 99%. Conclusion Among patients in sustained remission, patient-reported flare status was accurate in ruling out a clinically significant flare. About half of the patient-reported flares were assessed to be clinically significant. These findings support a potential for using patient-reported flare status in remote monitoring of patients with RA in sustained remission.

• Holten, Karen; Sundlisæter, Nina Paulshus; Sexton, Joseph; Nordberg, Lena Bugge; Uhlig, Till & Kvien, Tore Kristian Aaserud [Show all 10 contributors for this article] (2024). Performance of the Rheumatoid Arthritis Impact of Disease (RAID) score in relation to flares in disease activity. RMD Open. 10(1). doi: 10.1136/rmdopen-2023-003486. Full text in Research Archive Show summary

  Objectives To explore the performance of the EULAR-initiated patient-reported Rheumatoid Arthritis Impact of Disease (RAID) questionnaire in relation to flares in disease activity, including comparison with other disease activity outcomes. Methods Patients with rheumatoid arthritis in sustained remission were randomised to continued stable treatment or tapering in the ARCTIC REWIND project. In patients with flares within 12 months, we compared RAID (total score and components) at the flare visit with the visit prior to and the visit following flare, using Wilcoxon signed-rank test. Similar analyses were performed for patient global assessment, Disease Activity Score (DAS) and C reactive protein (CRP). The discriminative accuracies of RAID, patient global assessment, DAS and CRP with respect to disease activity flares were assessed by receiver operating characteristic (ROC) analyses based on logistic regression models. Flare was defined as a combination of DAS >1.6, a DAS increase ≥0.6 and ≥two swollen joints (of 44 examined) or could be recorded if patient and rheumatologist agreed that a clinically significant flare had occurred. Results In total, 248 patients were included in the analyses, with 56 flares. RAID, patient global assessment, DAS and CRP all changed significantly at the visits related to flare (p<0.001). Area under the curve (95% CI) values indicated that RAID (0.88 (0.83 to 0.93)) was significantly more accurate than CRP (0.76 (0.69 to 0.84)) in discriminating flare, and less accurate than patient global assessment (0.92 (0.87 to 0.97)) and DAS (0.94 (0.90 to 0.98)). The RAID components with highest and lowest discriminative accuracies were pain (0.91 (0.86 to 0.95)) and sleep (0.69 (0.59 to 0.79)). Conclusion Disease activity flares were associated with a significant increase in median RAID, supporting its ability to respond to flare.

• Ørbo, Hilde Sofie Sager; Kasahara, Taissa de Matos; Wolf, Asia-Sophia Fumika Michaela; Bjørlykke, Kristin Hammersbøen; Sexton, Joseph & Jyssum, Ingrid [Show all 24 contributors for this article] (2024). Humoral and cellular responses to a fifth bivalent SARS-CoV-2 vaccine dose in patients with immune-mediated inflammatory diseases on tumour necrosis factor inhibitors: a prospective cohort study. The Lancet Regional Health - Europe. 48. doi: 10.1016/j.lanepe.2024.101121. Full text in Research Archive Show summary

  Background As most people now have established hybrid immunity, the need for regular, updated SARS-CoV-2 vaccine boosters in patients with immune-mediated inflammatory diseases (IMIDs) is unclear. The study aim was to assess humoral and cellular immunogenicity of a fifth bivalent vaccine dose in patients with IMID on tumour necrosis factor inhibitors (TNFi). Methods In the longitudinal, observational Nor-vaC study, we assessed anti-spike and neutralising antibodies against Wuhan, Omicron BA.1 and BA.4, as well as frequency and polyfunctionality of responding T cells, following a fourth monovalent and a fifth bivalent (BA.1 or BA.4/5) vaccine dose in patients with or without hybrid immunity using TNFi. Findings Between December 17, 2021, and June 20, 2023, 456 infection-naïve patients with IMIDs using TNFi received a fourth vaccine dose and were otherwise eligible for inclusion. A total of 373/456 (82%) received a fifth vaccine dose, of these 190/373 (51%) had hybrid immunity defined as having had COVID-19 between the fourth and fifth dose. In patients with hybrid immunity, the fifth dose did not induce improved humoral responses compared to infection, neither with BA.1 (median anti-spike antibody concentrations 23,244 IU/ml (IQR 15,138–45,233) vs 36,341 IU/ml (11,887–53,710), p = 0.52) nor BA.4/5 (31,693 IU/ml (15,176–54,186), p = 0.30). Comparison of neutralising antibodies yielded similar results. In infection-naïve patients, a fifth BA.4/5 vaccine, but not the BA.1, induced slightly higher humoral responses (18,890 IU/ml (6494–50,211)) compared to the fourth dose (7304 IU/ml (3245–17,260), p < 0.0001). CD8 T cell responses remained stable following a fourth dose (median frequency of spike-specific cells 0.039% (IQR 0.010–0.14)), infection (0.058% (0.026–0.17)) and a fifth dose (0.058% (0.013–0.20). Interpretation In patients on TNFi with hybrid immunity, there was no immunological benefit of an updated fifth SARS-CoV-2 booster dose. Stable CD8 cellular responses following four doses indicate established protective immunity. Patients whose only risk factor is TNFi may in future follow vaccine recommendations for the general population.

• Gehin, Johanna; Klaasen, Rolf; Kristianslund, Eirik; Jyssum, Ingrid; Sexton, Joseph & Warren, David [Show all 11 contributors for this article] (2024). Therapeutic serum level for adalimumab in rheumatoid arthritis: explorative analyses of data from a randomised phase III trial. RMD Open. 10(4). doi: 10.1136/rmdopen-2024-004888. Full text in Research Archive Show summary

  Objectives The objectives of this study are to identify a therapeutic serum level for adalimumab associated with remission and low disease activity in patients with rheumatoid arthritis. Methods Associations between serum adalimumab trough levels and disease activity were examined using longitudinal data from a 48-week randomised phase III trial including patients with tumour necrosis factor inhibitor-naïve rheumatoid arthritis with active disease starting adalimumab treatment. Disease activity was classified according to 28-joint Disease Activity Score (DAS28)-erythrocyte sedimentation rate and C reactive protein (CRP) levels. Results Adalimumab trough levels were recorded longitudinally for 336, 330 and 302 patients at weeks 12, 24 and 48, respectively. All patients received concomitant methotrexate. Median adalimumab trough levels were 6.4 mg/L (IQR 3.4–9.5) at week 12, 7.5 mg/L (IQR 3.5–10.9) at week 24 and 7.6 mg/L (IQR 3.6–12.0) at week 48. In serial serum samples from weeks 12, 24 and 48, trough levels ≥3.9 mg/L were associated with DAS28 remission (OR 3.88 (95% CI 1.80, 8.38), p<0.001) and lower CRP levels (p<0.001). Week 12 trough levels ≥3.5 mg/L were associated with DAS28 low disease activity at week 24 (OR 2.62 (1.50, 4.56), p<0.001) and remission at week 48 (OR 1.99 (1.02, 3.88), p=0.04), as well as lower CRP levels at both time points (p<0.001). Conclusion Adalimumab trough levels above 4.0 mg/L were associated with remission/low disease activity throughout the first year of adalimumab therapy and can be considered a lower target level for therapeutic drug monitoring of adalimumab therapy.

• Vasileiadis, Georgios K.; Zhang, Yuan; Fatima, Tahzeeb; Vollenhoven, Ronald van; Lampa, Jon & Gudbjornsson, Bjorn [Show all 18 contributors for this article] (2024). Circulating Adipokines and Response to Treatment in Patients With Early Rheumatoid Arthritis. ACR Open Rheumatology. doi: 10.1002/acr2.11756. Full text in Research Archive Show summary

  Objective The objective of this study was to determine if baseline adiponectin, leptin, and resistin levels are associated with response to antirheumatic treatment in early rheumatoid arthritis (RA). Methods This study included 341 participants of the Nordic Rheumatic Diseases Strategy Trials and Registries trial with untreated early RA, randomized at baseline into four treatment arms: methotrexate combined with (1) prednisolone, (2) certolizumab, (3) abatacept, or (4) tocilizumab. Follow-up was up to 48 weeks. Adipokines were measured in plasma at baseline with enzyme-linked immunosorbent assay. The primary outcome for this report was the difference in remission (Clinical Disease Activity Index [CDAI] ≤2.8) over 48 weeks stratified by median adipokine levels. Results At baseline, levels of adiponectin and leptin were not associated with markers of RA activity, whereas participants with higher resistin levels had higher C-reactive protein (CRP) levels, swollen joint count, and Disease Activity Score in 28 joints based on CRP compared to participants with lower resistin. Overall, participants with baseline adipokine levels above the median and those with adipokine levels below the median had similar mean CDAI and changes in CDAI throughout follow-up for up to 48 weeks. Adjusted Cox proportional hazards models did not show any effect of baseline adiponectin, leptin, and resistin levels on the likelihood of achieving CDAI remission (adiponectin: hazard ratio [HR] 1.08, 95% confidence interval [CI] 0.80–1.45, P = 0.62; leptin: HR 0.89, 95% CI 0.64–1.26, P = 0.52; resistin: HR 0.86, 95% CI 0.65–1.13, P = 0.26). Conclusion Baseline adiponectin, leptin, and resistin levels are not associated with the likelihood of achieving CDAI remission over 48 weeks of treatment in a large cohort of people with untreated early RA.

• Dubovyk, Violetta; Vasileiadis, Georgios K.; Fatima, Tahzeeb; Zhang, Yuan; Kapetanovic, Meliha Crnkic & Kastbom, Alf [Show all 25 contributors for this article] (2024). Obesity is a risk factor for poor response to treatment in early rheumatoid arthritis: a NORD-STAR study. RMD Open. 10(2). doi: 10.1136/rmdopen-2024-004227. Full text in Research Archive Show summary

  Objective This report from the NORD-STAR (Nordic Rheumatic Diseases Strategy Trials and Registries) trial aimed to determine if obesity is associated with response to conventional and biological antirheumatic treatment in early rheumatoid arthritis (RA). Methods This report included 793 participants with untreated early RA from the randomised, longitudinal NORD-STAR trial, all of whom had their body mass index (BMI) assessed at baseline. Obesity was defined as BMI ≥30 kg/m2. All participants were randomised 1:1:1:1 to one of four treatment arms: active conventional treatment, certolizumab-pegol, abatacept and tocilizumab. Clinical and laboratory measurements were performed at baseline and at 8, 12, 24 and 48-week follow-up. The primary endpoint for this report was response to treatment based on Clinical Disease Activity Index (CDAI) and Simple Disease Activity Index (SDAI) remission and Disease Activity Score with 28 joints using C-reactive protein (DAS28-CRP) <2.6 stratified by BMI. Results Out of 793 people included in the present report, 161 (20%) had obesity at baseline. During follow-up, participants with baseline obesity had higher disease activity compared with those with lower BMI, despite having similar disease activity at baseline. In survival analyses, obesity was associated with a lower likelihood of achieving response to treatment during follow-up for up to 48 weeks (CDAI remission, HR 0.84, 95% CI 0.67 to 1.05; SDAI, HR 0.77, 95% CI 0.62 to 0.97; DAS28-CRP <2.6, HR 0.78, 95% CI 0.64 to 0.95). The effect of obesity on response to treatment was not influenced by the treatment arms. Conclusion In people with untreated early RA followed up for up to 48 weeks, obesity was associated with a lower likelihood of good treatment response, irrespective of the type of randomised treatment received.

• Kjørholt, Kaja Eriksrud; Sundlisæter, Nina Paulshus; Aga, Anna-Birgitte; Sexton, Joseph; Olsen, Inge Christoffer & Fremstad, Hallvard [Show all 22 contributors for this article] (2024). Effects of tapering conventional synthetic disease-modifying antirheumatic drugs to drug-free remission versus stable treatment in rheumatoid arthritis (ARCTIC REWIND): 3-year results from an open-label, randomised controlled, non-inferiority trial. The Lancet Rheumatology. 6(5), p. e268–e278. doi: 10.1016/S2665-9913(24)00021-3. Full text in Research Archive Show summary

  Background Tapering of disease-modifying antirheumatic drugs (DMARDs) to drug-free remission is an attractive treatment goal for patients with rheumatoid arthritis, although long-term effects of tapering and withdrawal remain unclear. We compared 3-year risks of flare between three conventional synthetic DMARD treatment strategies in patients with rheumatoid arthritis in sustained remission. Methods In this open-label, randomised controlled, non-inferiority trial, we enrolled patients aged 18–80 years with rheumatoid arthritis who had been in sustained remission for at least 1 year on stable conventional synthetic DMARD therapy. Patients from ten hospitals in Norway were randomly assigned (2:1:1) with centre stratification to receive stable conventional synthetic DMARDs, half-dose conventional synthetic DMARDs, or half-dose conventional synthetic DMARDs for 1 year followed by withdrawal of all conventional synthetic DMARDs. The primary endpoint of this part of the study was disease flare over 3 years, analyse

• Ørbo, Hilde Sofie Sager; Hammersbøen, Kristin Reine; Sexton, Joseph; Jyssum, Ingrid; Tveter, Anne Therese & Christensen, Ingrid Egeland [Show all 18 contributors for this article] (2024). Incidence and outcome of COVID-19 following vaccine and hybrid immunity in patients on immunosuppressive therapy: identification of protective post-immunisation anti-RBD antibody levels in a prospective cohort study. RMD Open. 10(2). doi: 10.1136/rmdopen-2023-003545. Full text in Research Archive Show summary

  Objectives To assess incidence, severity and predictors of COVID-19, including protective post-vaccination levels of antibodies to the receptor-binding domain of SARS-CoV-2 spike protein (anti-RBD), informing further vaccine strategies for patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive medication. Methods IMIDs on immunosuppressives and healthy controls (HC) receiving SARS-CoV-2 vaccines were included in this prospective observational study. COVID-19 and outcome were registered and anti-RBD antibodies measured 2–5 weeks post-immunisation. Results Between 15 February 2021 and 15 February 2023, 1729 IMIDs and 350 HC provided blood samples and self-reported COVID-19. The incidence of COVID-19 was 66% in patients and 67% in HC, with re-infection occurring in 12% of patients. Severe COVID-19 was recorded in 22 (2%) patients and no HC. No COVID-19-related deaths occurred. Vaccine-induced immunity gave higher risk of COVID-19 (HR 5.89 (95% CI 4.45 to 7.80)) than hybrid immunity. Post-immunisation anti-RBD levels <6000 binding antibody units/mL were associated with an increased risk of COVID-19 following three (HR 1.37 (95% CI 1.08 to 1.74)) and four doses (HR 1.28 (95% CI 1.02 to 1.62)), and of COVID-19 re-infection (HR 4.47 (95% CI 1.87 to 10.67)). Conclusion Vaccinated patients with IMID have a low risk of severe COVID-19. Hybrid immunity lowers the risk of infection. High post-immunisation anti-RBD levels protect against COVID-19. These results suggest that knowledge on COVID-19 history, and assessment of antibody levels post-immunisation can help individualise vaccination programme series in high-risk individuals. Trial registration number NCT04798625.

• Scheffler, Julia M.; Drevinge, Christina; Lindholm, Catharina; Gjertsson, Inger; Lend, Kristina & Hetland, Merete Lund [Show all 23 contributors for this article] (2024). Circulating Baseline CXCR3⁺Th2 and Th17 Cell Proportions Correlate With Trabecular Bone Loss After 48 Weeks of Biological Treatment in Early Rheumatoid Arthritis. ACR Open Rheumatology. doi: 10.1002/acr2.11742. Full text in Research Archive Show summary

  Objective The high prevalence of osteoporosis in rheumatoid arthritis (RA) is due to inflammation that stimulates differentiation of osteoclasts, a process involving circulating monocytes and T cell–derived factors. The aim of this study was to evaluate relations between circulating monocytes, T cell subsets, and changes in bone characteristics before and after treatment with biological disease-modifying antirheumatic drugs (bDMARDs) in RA. Methods Thirty patients with untreated early RA who met the American College of Rheumatology/EULAR 2010 criteria were included. Data were collected before and 48 weeks after treatment with methotrexate (MTX) together with one of three bDMARDs (abatacept, tocilizumab, or certolizumab pegol). Disease activity was measured using the Clinical Disease Activity Index, swollen or tender joint counts, C-reactive protein levels, and erythrocyte sedimentation rates. Proportions of monocyte and CD4+ T cell subsets in blood samples were analyzed by flow cytometry. Bone densitometry was performed using high-resolution peripheral quantitative computed tomography (HR-pQCT). Results HR-pQCT revealed an overall decrease in cortical (P = 0.009) and trabecular (P = 0.034) bone mineral density, although a subset of patients showed no bone loss after 48 weeks of treatment. The overall bone loss was not associated with age, body mass index, sex, intraarticular glucocorticoid injections, or baseline disease activity. Loss of trabecular bone volume fraction correlated with high proportions of circulating CXCR3+Th2 cells (r = −0.38, P = 0.04) and CXCR3+Th17 cells (r = −0.36, P = 0.05) at baseline. Similarly, no loss of trabecular bone volume fraction correlated with high proportions of regulatory T cells (r = 0.4, P = 0.03) at baseline. However, the associations were not significant when corrected for confounders and multiple testing. Conclusion MTX together with bDMARDs efficiently reduce disease activity but only prevent bone loss in a subset of patients with RA after 48 weeks of treatment. The correlations of circulating baseline T helper cell and regulatory T cell populations with trabecular bone changes suggest a potential novel role for these cells in systemic bone homeostasis during early RA.

• Uhlig, Tillmann; Karoliussen, Lars Fridtjof; Sexton, Joseph; Provan, Sella Aarrestad; Haavardsholm, Espen Andre & Hammer, Hilde Berner (2024). Non-adherence to urate lowering therapy in gout after 5 years is related to poor outcomes: results from the NOR-Gout study. Rheumatology. ISSN 1462-0324. 64(4), p. 1799–1806. doi: 10.1093/rheumatology/keae514. Full text in Research Archive Show summary

  Objectives Patients with gout need to adhere to medication over time to achieve good outcomes. We assessed self-reported adherence to medication with urate lowering therapy (ULT) 5 years after a treat-to-target intervention and studied how non-adherence was related to baseline demographic and disease variables. Methods Patients in the NOR-Gout observational study were included after a recent gout flare and serum urate >360 µmol/l. Patients [mean age 56.2 (S.D. 13.6), 94.5% males, 17.2% with tophi] attended tight-control visits over one year with escalating urate lowering therapy using a treat-to-target strategy. Five-year follow-up included the Medication Adherence Report Scale (MARS-5) questionnaire (range 5–25) for adherence. Flares and SUA target achievement were compared for 5-year adherence to medication. Results At 5 years most of the 163 patients used ULT (95.1%). MARS-5 adherence scores after 5 years were high (median 24, interquartile range 22–25). Patients in the lowest MARS-5 quartile had, compared with the highest quartile, more often a flare during the last year of follow-up (33.3% vs 9.5%, P = 0.004) and reached the 5-yr serum urate treatment target less frequently (45.2% vs 87.5%, P < 0.001). Baseline lower age (OR 0.56, 95%CI 0.39–0.79), non-European origin (OR 0.22, 95%CI 0.06–0.80), lower SF-36 mental health scores (OR 0.94, 95%CI 0.91–0.98) and less joint pain during last flare (OR 0.73, 95%CI 0.58–0.92) were independent risk factors for non-adherence to medication. Conclusions Patients reported high adherence to medication after 5 years. Non-adherence was related to more flares and less urate target achievement. Younger age and non-European origin were associated with non-adherence.

• Lend, Kristina; Lampa, Jon; Padyukov, Leonid; Hetland, Merete Lund; Schrumpf, Marte & Nordström, Dan C [Show all 21 contributors for this article] (2024). Association of rheumatoid factor, anti-citrullinated protein antibodies and shared epitope with clinical response to initial treatment in patients with early rheumatoid arthritis: data from a randomised controlled trial. Annals of the Rheumatic Diseases. ISSN 0003-4967. doi: 10.1136/ard-2024-226024. Full text in Research Archive Show summary

  Objectives To investigate whether rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPAs) and shared epitope (SE) allele-related genetic markers associate with treatment response to abatacept, certolizumab pegol or tocilizumab versus active conventional treatment (ACT). Methods Patients with treatment-naïve early rheumatoid arthritis were randomised in the NORD-STAR trial to ACT, certolizumab pegol, abatacept or tocilizumab, all with methotrexate. Centralised laboratory analyses for ACPA, RF and SE were performed. Clinical Disease Activity Index remission was analysed longitudinally with logistic generalised estimating equations. Differences in treatment effect across RF, ACPA and SE subgroups were assessed with interaction terms at 24 and 48 weeks, adjusted for sex, country, age, body mass index, Disease Activity Score of 28 joints based on C-reactive protein and smoking. Results In total, 778 patients were included. At 24 weeks, abatacept treatment showed a better response than ACT in the RF and/or ACPA-positive subgroups, but this effect was not significantly different from the negative subgroups. By 48 weeks, abatacept treatment showed better response regardless of RF/ACPA status. No differences were found across RF, ACPA, SE allele, valine at amino acid position 11 or valine-arginine-alanine haplotype subgroups for any biological treatment at 48 weeks. Conclusions Based on this randomised controlled trial, abatacept treatment was associated with a better response than ACT in the RF and/or ACPA-positive subgroup at 24 weeks, but this was no longer seen at 48 weeks; adding SE allele-related genetic markers did not strengthen the association. Moreover, ACPA, RF and SE allele-related genotypes were not, alone or in combination, associated with clinical responses of importance sufficiently strongly to warrant implementation in clinical practice.

• Dijkshoorn, Bas; Hansildaar, Romy; Vedder, Daisy; Soutari, Nida; Rudin, Anna & Nordström, Dan [Show all 19 contributors for this article] (2024). Impaired coagulation parameters in early RA are restored by effective antirheumatic therapy: a prospective pilot study. RMD Open. 10(4). doi: 10.1136/rmdopen-2024-004838. Full text in Research Archive Show summary

  Objectives To assess the effect of treatment on haemostatic parameters in patients with early rheumatoid arthritis (RA). Methods Patients with newly diagnosed RA started methotrexate and were randomised to additional conventional treatment, certolizumab pegol, abatacept or tocilizumab. Several biomarkers for haemostasis were analysed including parameters of the two global haemostatic assays—overall haemostatic potential (OHP) and endogenous thrombin potential (ETP), as well as single haemostatic factors—fibrinogen, prothrombin fragment 1+2 (F1+2), D-dimer, thrombin activatable fibrinolysis inhibitor (TAFI) and clot lysis time (CLT) in 24 patients at baseline, 12 and 24 weeks after the start of the treatment. Results At baseline, patients had elevated levels of the following biomarkers compared with reference values: fibrinogen, F1+2, D-dimer and parameters of the two global haemostatic assays, that is, ETP and OHP. After 24 weeks we observed a significant reduction in F1+2 (p<0.01), fibrinogen (p<0.01), D-dimer (p<0.01), OHP (p<0.01), ETP (p<0.01), CLT (p<0.01), TAFI (p<0.01) and an increase of OFP (p<0.01). Tocilizumab treatment resulted in the most significant reduction of global haemostatic assays after 24 weeks, that is, a reduction of OHP 73% (p<0.01) compared with certolizumab pegol arm 32% (p<0.01), abatacept arm 24% (p=0.25) or conventional treatment arm 7% (p=0.66). Conclusion Newly diagnosed RA patients have enhanced coagulation activation and impaired fibrinolysis as demonstrated by our results. Effective antirheumatic treatments during the first 24 weeks after diagnosis improved this haemostatic imbalance, with prominent effects of biological drugs and especially tocilizumab, compared with conventional treatment.

• Brun, Marthe Kirkesæther; Hammersbøen, Kristin Reine; Viken, Marte Kathrine; Stenvik, Grethe-Elisabeth; Klaasen, Rolf & Gehin, Johanna [Show all 18 contributors for this article] (2023). HLA-DQ2 is associated with anti-drug antibody formation to infliximab in patients with immune-mediated inflammatory diseases. Journal of Internal Medicine. ISSN 0954-6820. 293(5), p. 648–655. doi: 10.1111/joim.13616. Full text in Research Archive Show summary

  Abstract Background Immunogenicity to tumour necrosis factor inhibitors is a significant clinical problem leading to treatment failure and adverse events. The study aimed to assess human leukocyte antigen (HLA) associations with anti‐drug antibody (ADAb) formation to infliximab. Methods Immune‐mediated inflammatory disease patients on infliximab therapy ( n  = 612) were included. Neutralising ADAb were assessed with a drug‐sensitive assay. Next generation sequencing‐based HLA typing was performed. Results Overall, 147 (24%) patients developed ADAb. Conditional analyses indicated HLA‐DQB1 ( p  = 1.4 × 10 −6 ) as a primary risk locus. Highest risk of ADAb was seen when carrying at least one of the HLA‐DQ2 haplotypes; DQB1*02:01–DQA1*05:01 or DQB1*02:02–DQA1*02:01 (OR 3.18, 95% CI 2.15–4.69 and p  = 5.9 × 10 −9 ). Results were consistent across diseases and when adjusting for concomitant immunomodulator. Computational predictions indicated that these HLA‐DQ2 haplotypes bind to peptide motifs from infliximab light chain. Conclusion A genome‐wide significant association between two HLA‐DQ2 haplotypes and the risk of ADAb formation to infliximab was identified, suggesting that HLA‐DQ2 testing may facilitate personalised treatment decisions.

• Brkic, Alen; Diamantopoulos, Andreas P; Hoff, Mari; Haavardsholm, Espen A.; Fevang, Bjørg Tilde Svanes & Brekke, Lene Kristin [Show all 11 contributors for this article] (2023). Exploring the impact of the national tender system on the use of costly drugs treating rheumatoid arthritis patients in ten rheumatology centers in Norway (2010–2019). BMC Health Services Research. 23(1). doi: 10.1186/s12913-023-09975-7. Full text in Research Archive Show summary

  Background Biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) are highly effective in treating rheumatoid arthritis (RA), albeit high drug cost has restricted their use in many countries. As a countermeasure, Norway implemented pharmaceutical tendering as a cost-reducing strategy. The aim of this study was to assess the annual proportion of different b/tsDMARDs registered to treat RA patients under the influence of a Norwegian pharmaceutical tendering between 2010 and 2019. Method The data is collected from ten Norwegian outpatient centers. The included patients are categorized as naïve, non-naïve, and current b/tsDMARD users. 13 individual b/tsDMARDs are assessed and compared with the tender rankings from each year. Overview of subcutaneous (sc) with per oral vs. intravenous (iv) and biosimilars vs. non-biosimilar are also described. Result The tender-winning b/tsDMARD was the most or second most used drug in nine out of ten years for naïve users, seven for non-naïve users, and twice for current users. The average sum of the highest and second highest proportion among naïve, non-naïve, and current b/tsDMARD users were 75%, 53%, and 50% during the ten years, respectively. The tender-winning drug was iv in eight out of ten years. However, the average total proportion of sc and per oral b/tsDMARDs was about 70% for naïve b/tsDMARD users, 50% for non-naïve b/tsDMARD users, and 60% for current b/tsDMARD users. The main contributors to sc and per oral b/tsDMARD were etanercept (reference and biosimilar) and certolizumab pegol. The main contributors to iv b/tsDMARD were rituximab reference and infliximab biosimilar. Despite low-ranking offers, rituximab reference (offered as a second-line drug) often achieved a high proportion among non-naïve and current b/tsDMARD users. After the introduction of biosimilars, their average proportion was about 40%, 40%, and 20% for naïve, non-naïve, and current b/tsDMARD users, respectively. Conclusion Based on observed data, a higher tender rank was associated with a higher proportion among naïve and non-naïve b/tsDMARD users. However, in most cases, sc b/tsDMARDs achieved a higher proportion with lower tender ranks than iv b/tsDMARDs with higher tender ranks.

• Jyssum, Ingrid; Gehin, Johanna; Sexton, Joseph; Kristianslund, Eirik; Hu, Yi & Warren, David [Show all 11 contributors for this article] (2023). Adalimumab serum levels and anti-drug antibodies: associations to treatment response and drug survival in inflammatory joint diseases. Rheumatology. ISSN 1462-0324. 63(6), p. 1746–1755. doi: 10.1093/rheumatology/kead525. Full text in Research Archive Show summary

  Abstract Objectives To explore associations between serum adalimumab level, treatment response and drug survival in order to identify optimal drug levels for therapeutic drug monitoring of adalimumab. Also, to assess the occurrence and risk factors of anti-drug antibody (ADAb) formation. Methods Non-trough adalimumab and ADAb levels were measured by automated fluorescence assays in serum collected after 3 months of adalimumab treatment in patients with RA, PsA or axial SpA (axSpA) included in the observational NOR-DMARD study. Treatment response was evaluated after 3 months and drug survival was evaluated during long-term follow-up. Results In 340 patients (97 RA, 69 PsA, 174 axSpA), the median adalimumab level was 7.3 mg/l (interquartile range 4.0–10.3). A total of 33 (10%) patients developed ADAbs. Findings were comparable across diagnoses. In RA and PsA, adalimumab levels ≥6.0 mg/l were associated with treatment response [odds ratio (OR) 2.2 (95% CI 1.0, 4.4)] and improved drug survival [hazard ratio 0.49 (95% CI 0.27, 0.80)]. In axSpA, a therapeutic level could not be identified, but higher adalimumab levels were associated with response. Factors associated with ADAb formation were previous bDMARD use, no methotrexate comedication and the use of adalimumab originator compared with GP2017. Conclusion Higher adalimumab levels were associated with a better response and improved drug survival for all diagnoses, with a suggested lower threshold of 6.0 mg/l for RA/PsA. This finding, the large variability in drug levels among patients receiving standard adalimumab dose and the high proportion of patients developing ADAbs encourages further investigations into the potential role of therapeutic drug monitoring of adalimumab.

• Lillegraven, Siri; Sundlisæter, Nina Paulshus; Aga, Anna-Birgitte; Sexton, Joseph; Solomon, Daniel H. & Heijde, Désirée Van Der [Show all 7 contributors for this article] (2023). Discontinuation of Conventional Synthetic Disease-Modifying Antirheumatic Drugs in Patients with Rheumatoid Arthritis and Excellent Disease Control. Journal of the American Medical Association (JAMA). ISSN 0098-7484. 329(12), p. 1024–1026. doi: 10.1001/jama.2023.0492. Full text in Research Archive
• Østergaard, Mikkel; Vollenhoven, Ronald F Van; Rudin, Anna; Hetland, Merete Lund; Schrumpf, Marte & Nordström, Dan C [Show all 45 contributors for this article] (2023). Certolizumab pegol, abatacept, tocilizumab or active conventional treatment in early rheumatoid arthritis: 48-week clinical and radiographic results of the investigator-initiated randomised controlled NORD-STAR trial. Annals of the Rheumatic Diseases. ISSN 0003-4967. 82(10), p. 1286–1295. doi: 10.1136/ard-2023-224116. Full text in Research Archive Show summary

  Background - The optimal first-line treatment in early rheumatoid arthritis (RA) is debated. We compared clinical and radiographic outcomes of active conventional therapy with each of three biological treatments with different modes of action. Methods - Investigator-initiated, randomised, blinded-assessor study. Patients with treatment-naïve early RA with moderate–severe disease activity were randomised 1:1:1:1 to methotrexate combined with (1) active conventional therapy: oral prednisolone (tapered quickly, discontinued at week 36) or sulfasalazine, hydroxychloroquine and intra-articular glucocorticoid injections in swollen joints; (2) certolizumab pegol; (3) abatacept or (4) tocilizumab. Coprimary endpoints were week 48 Clinical Disease Activity Index (CDAI) remission (CDAI ≤2.8) and change in radiographic van der Heijde-modified Sharp Score, estimated using logistic regression and analysis of covariance, adjusted for sex, anticitrullinated protein antibody status and country. Bonferroni’s and Dunnet’s procedures adjusted for multiple testing (significance level: 0.025). Results - Eight hundred and twelve patients were randomised. Adjusted CDAI remission rates at week 48 were: 59.3% (abatacept), 52.3% (certolizumab), 51.9% (tocilizumab) and 39.2% (active conventional therapy). Compared with active conventional therapy, CDAI remission rates were significantly higher for abatacept (adjusted difference +20.1%, p<0.001) and certolizumab (+13.1%, p=0.021), but not for tocilizumab (+12.7%, p=0.030). Key secondary clinical outcomes were consistently better in biological groups. Radiographic progression was low, without group differences. The proportions of patients with serious adverse events were abatacept, 8.3%; certolizumab, 12.4%; tocilizumab, 9.2%; and active conventional therapy, 10.7%. Conclusions - Compared with active conventional therapy, clinical remission rates were superior for abatacept and certolizumab pegol, but not for tocilizumab. Radiographic progression was low and similar between treatments.

• Berg, Inger Jorid; Tveter, Anne Therese; Bakland, Gunnstein; Hakim, Sarah; Kristianslund, Eirik & Lillegraven, Siri [Show all 15 contributors for this article] (2023). Follow-Up of Patients With Axial Spondyloarthritis in Specialist Health Care With Remote Monitoring and Self-Monitoring Compared With Regular Face-to-Face Follow-Up Visits (the ReMonit Study): Protocol for a Randomized, Controlled Open-Label Noninferiority Trial. JMIR Research Protocols. 12(1), p. e52872–e52872. doi: 10.2196/52872. Full text in Research Archive Show summary

  Background: Patients with chronic inflammatory joint diseases such as axial spondyloarthritis have traditionally received regular follow-up in specialist health care to maintain low disease activity. The follow-up has been organized as prescheduled face-to-face visits, which are time-consuming for both patients and health care professionals. Technology has enabled the remote monitoring of disease activity, allowing patients to self-monitor their disease and contact health care professionals when needed. Remote monitoring or self-monitoring may provide a more personalized follow-up, but there is limited research on how these follow-up strategies perform in maintaining low disease activity, patient satisfaction, safety, and cost-effectiveness.<p> <p>Objective: The Remote Monitoring in Axial Spondyloarthritis (ReMonit) study aimed to assess the effectiveness of digital remote monitoring and self-monitoring in maintaining low disease activity in patients with axial spondyloarthritis.<p> <p>Methods: The ReMonit study is a 3-armed, single-site, randomized, controlled, open-label noninferiority trial including patients with axial spondyloarthritis with low disease activity (Ankylosing Spondylitis Disease Activity Score <2.1) and on stable treatment with a tumor necrosis factor inhibitor. Participants were randomized 1:1:1 to arm A (usual care, face-to-face visits every sixth month), arm B (remote monitoring, monthly digital registration of patient-reported outcomes), or arm C (patient-initiated care, self-monitoring, no planned visits during the study period). The primary end point was disease activity measured with the Ankylosing Spondylitis Disease Activity Score, evaluated at 6, 12, and 18 months. We aimed to include 240 patients, 80 in each arm. Secondary end points included other measures of disease activity, patient satisfaction, safety, and cost-effectiveness.<p> <p>Results: The project is funded by the South-Eastern Norway Regional Health Authority and Centre for the treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Norway. Enrollment started in September 2021 and was completed with 242 patients by June 2022. The data collection will be completed in December 2023.<p> <p>Conclusions: To our knowledge, this trial will be among the first to evaluate the effectiveness, safety, and cost-effectiveness of remote digital monitoring and self-monitoring of patients with axial spondyloarthritis compared with usual care. Hence, the ReMonit study will contribute important knowledge to personalized follow-up strategies for patients with axial spondyloarthritis. These results may also be relevant for other patient groups with inflammatory joint diseases.

• Lend, Kristina; Koopman, Frieda A.; Lampa, Jon; Jansen, Gerrit; Hetland, Merete L. & Uhlig, Till [Show all 18 contributors for this article] (2023). Methotrexate Safety and Efficacy in Combination Therapies in Patients With Early Rheumatoid Arthritis: A Post Hoc Analysis of a Randomized Controlled Trial. Arthritis & Rheumatology. ISSN 2326-5191. p. 1–14. doi: 10.1002/art.42730. Full text in Research Archive Show summary

  Objective We investigated methotrexate safety and the influence of dose on efficacy outcomes in combination with three different biologic treatments and with active conventional treatment (ACT) in early rheumatoid arthritis (RA). Methods This post hoc analysis included 812 treatment-naïve patients with early RA who were randomized (1:1:1:1) in the NORD-STAR trial to receive methotrexate in combination with ACT, certolizumab-pegol, abatacept, or tocilizumab. Methotrexate safety, doses, and dose effects on Clinical Disease Activity Index (CDAI) remission were assessed after 24 weeks of treatment. Results Compared with ACT, the prevalence of methotrexate-associated side effects was higher when methotrexate was combined with tocilizumab (hazard ratio [HR] 1.48, 95% confidence interval [CI] 1.20–1.84) but not with certolizumab-pegol (HR 0.99, 95% CI 0.79–1.23) or with abatacept (HR 0.93, 95% CI 0.75–1.16). With ACT as the reference, the methotrexate dose was significantly lower when used in combination with tocilizumab (β −4.65, 95% CI −5.83 to −3.46; P < 0.001) or abatacept (β −1.15, 95% CI −2.27 to −0.03; P = 0.04), and it was numerically lower in combination with certolizumab-pegol (β −1.07, 95% CI −2.21 to 0.07; P = 0.07). Methotrexate dose reductions were not associated with decreased CDAI remission rates within any of the treatment combinations. Conclusion Methotrexate was generally well tolerated in combination therapies, but adverse events were a limiting factor in receiving the target dose of 25 mg/wk, and these were more frequent in combination with tocilizumab versus ACT. On the other hand, methotrexate dose reductions were not associated with decreased CDAI remission rates within any of the four treatment combinations at 24 weeks.

• Lillegraven, Siri; Sundlisæter, Nina Paulshus; Aga, Anna-Birgitte; Sexton, Joseph; Olsen, Inge Christoffer & Lexberg, Åse [Show all 19 contributors for this article] (2023). Effect of tapered versus stable treatment with tumour necrosis factor inhibitors on disease flares in patients with rheumatoid arthritis in remission: a randomised, open label, non-inferiority trial. Annals of the Rheumatic Diseases. ISSN 0003-4967. 82(11), p. 1394–1403. doi: 10.1136/ard-2023-224476. Full text in Research Archive Show summary

  Objectives Many patients with rheumatoid arthritis (RA) require treatment with tumour necrosis factor inhibitor (TNFi) to reach remission. It is debated whether tapering of TNFi to discontinuation should be considered in sustained remission. The aim of ARCTIC REWIND TNFi was to assess the effect of tapering TNFi to withdrawal compared with stable treatment on the risk of disease activity flares in patients with RA in remission ≥1 year. Methods This randomised, open-label, non-inferiority trial was undertaken at nine Norwegian rheumatology departments. Patients with RA in remission ≥12 months on stable TNFi therapy were allocated by computer-based block-randomisation to tapering to discontinuation of TNFi or stable TNFi. Conventional synthetic disease-modifying antirheumatic co-medication was unchanged. The primary endpoint was disease flare during the 12-month study period (non-inferiority margin 20%), assessed in the per-protocol population. Results Between June 2013 and January 2019, 99 patients were enrolled and 92 received the allocated treatment strategy. Eighty-four patients were included in the per-protocol population. In the tapering TNFi group, 27/43 (63%) experienced a flare during 12 months, compared with 2/41 (5%) in the stable TNFi group; risk difference (95% CI) 58% (42% to 74%). The tapering strategy was not non-inferior to continued stable treatment. The number of total/serious adverse events was 49/3 in the tapering group, 57/2 in the stable group. Conclusion In patients with RA in remission for more than 1 year while using TNFi, an increase in flare rate was reported in those who tapered TNFi to discontinuation. However, most regained remission after reinstatement of full-dose treatment.

• Uhlig, Till; Karoliussen, Lars Fridtjof; Sexton, Joseph; Provan, Sella Aarrestad; Kvien, Tore Kristian Aaserud & Haavardsholm, Espen A. [Show all 7 contributors for this article] (2023). Course and predictors of work productivity in gout - results from the NOR-Gout longitudinal 2-year treat-to-target study. Rheumatology. ISSN 1462-0324. 62(12), p. 3886–3892. doi: 10.1093/rheumatology/kead124. Full text in Research Archive Show summary

  Objectives In patients with gout there is a lack of longitudinal studies on the course of work productivity. We explored longitudinal changes in and predictors of work productivity over 2 years. Methods Patients in the NOR-Gout observational study with a recent gout flare and serum urate (sUA) >360 µmol/l attended tight-control visits during escalating urate lowering therapy according to a treat-to-target strategy. From the Work Productivity and Activity Impairment (WPAI) questionnaire, scores for work productivity and activity impairment were assessed over 2 years together with the Beliefs about Medicines Questionnaire and a variety of demographic and clinical variables. Results At baseline patients had a mean age of 56.4 years and 95% were males. WPAI scores at baseline were 5.0% work missed (absenteeism), 19.1% work impairment (presenteeism), 21.4% overall work impairment and 32.1% activity impairment. Work productivity and activity impairment improved during the first months, and remained stable at 1 and 2 years. Comorbidities were not cross-sectionally associated with WPAI scores at baseline, but predicted worse work impairment and activity impairment at year 1. The Beliefs about Medicines Questionnaire subscale with concerns about medicines at baseline independently predicted worse overall work impairment and worse activity impairment at year 1. Conclusions In patients with gout who were intensively treated to the sUA target, work productivity and activity impairment were largely unchanged and at 1 year predicted by comorbidities and patient concerns about medication.

• Uhlig, Till; Karoliussen, Lars Fridtjof; Sexton, Joseph; Kvien, Tore Kristian Aaserud; Haavardsholm, Espen A. & Taylor, W.J. [Show all 7 contributors for this article] (2023). Beliefs about medicines in gout patients: results from the NOR-Gout 2-year study. Scandinavian Journal of Rheumatology. ISSN 0300-9742. doi: 10.1080/03009742.2023.2213507. Full text in Research Archive Show summary

  Objective Adherence to urate-lowering therapy (ULT) in gout is challenging. This longitudinal study aimed to determine 2 year changes in beliefs about medicines during intervention with ULT. Method Patients with a recent gout flare and increased serum urate received a nurse-led ULT intervention with tight control visits and a treatment target. Frequent visits at baseline and 1, 2, 3, 6, 9, 12, and 24 months included the Beliefs about Medicines Questionnaire (BMQ), and demographic and clinical variables. The BMQ subscales on necessity, concerns, overuse, harm, and the necessity–concerns differential were calculated as a measure of whether the patient perceived that necessity outweighed concerns. Results The mean serum urate reduced from 500 mmol/L at baseline to 324 mmol/L at year 2. At years 1 and 2, 85.5% and 78.6% of patients, respectively, were at treatment target. The 2 year mean ± sd BMQ scores increased for the necessity subscale from 17.0 ± 4.4 to 18.9 ± 3.6 (p < 0.001) and decreased for the concerns subscale from 13.4 ± 4.9 to 12.5 ± 2.7 (p = 0.001). The necessity–concerns differential increased from 3.52 to 6.58 (p < 0.001), with a positive change independent of patients achieving treatment targets at 1 or 2 years. BMQ scores were not significantly related to treatment outcomes 1 or 2 years later, and achieving treatment targets did not lead to higher BMQ scores. Conclusion Patient beliefs about medicines improved gradually over 2 years, with increased beliefs in the necessity of medication and reduced concerns, but this improvement was unrelated to better outcomes.

• Uhlig, Till; Karoliussen, Lars Fridtjof; Sexton, Joseph; Kvien, Tore Kristian Aaserud; Haavardsholm, Espen A. & Hammer, Hilde Berner (2023). Lifestyle factors predict gout outcomes: Results from the NOR-Gout longitudinal 2-year treat-to-target study. RMD Open. 9(4). doi: 10.1136/rmdopen-2023-003600. Full text in Research Archive Show summary

  Objective Gout is associated with lifestyle, body mass index (BMI) and comorbidities, including dyslipidaemia. We studied how in actively treated patients, anthropometric measures and lipid levels changed over 2 years and whether they predicted gout outcomes. Methods Patients with a recent gout flare and elevated serum urate (sUA) received gout education and treat-to-target urate-lowering therapy over 1 year. Anthropometric measures with BMI, waist circumference (WC) and waist–height ratio (WHR) as well as lipid levels were measured yearly over 2 years. We examined whether baseline anthropometric measures and lipid levels were related to flares and to achieving the sUA target. Results At baseline, patients (n=211) were with mean age of 56.4 years and 95% were male. Over 2 years, anthropometric measures were largely unchanged while cholesterol and low-density lipoprotein cholesterol (LDL-C) were reduced at year 1. Anthropometric measures were associated with presence of tophi. Higher baseline WC (OR: 0.96 per cm, 95% CI: 0.93 to 0.99) decreased and high level of high-density lipoprotein cholesterol (OR: 5.1 per mmol/L, 95% CI: 1.2 to 22.1) increased the chance of sUA target achievement at year 2. High LDL-C (OR: 1.8 per mmol/L, 95% CI: 1.2 to 2.6) predicted the chance of having a gout flare during year 2. Conclusion In actively treated patients with gout, anthropometric measures were largely unchanged over 2 years and lipid levels were reduced. High WC and lipid levels predicted unfavourable gout outcomes after 2 years.

• Hammer, Hilde Berner; Pedersen, Sigve Lars; Jonsson, Maria Karolina; Mathsson-Alm, Linda; Gehring, Isabel & Sexton, Joseph [Show all 8 contributors for this article] (2023). Calprotectin, a sensitive marker of inflammation, is robustly assessed in plasma from patients with early or established rheumatoid arthritis by use of different laboratory methods. Scandinavian Journal of Clinical and Laboratory Investigation. ISSN 0036-5513. 83(5), p. 330–335. doi: 10.1080/00365513.2023.2225223. Full text in Research Archive Show summary

  Calprotectin (S100A8/S100A9, MRP8/MRP14) is a major leukocyte protein found to be more sensitive than C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR) as a marker of inflammation in patients with rheumatoid arthritis (RA). The present objective was to explore the robustness of calprotectin assessments by comparing two different laboratory methods assessing calprotectin in plasma samples from patients with early or established RA. A total of 212 patients with early RA (mean (SD) age 52(13.3) years, disease duration 0.6(0.5) years) and 177 patients with established RA (mean (SD) age 52.9(13.0) years, disease duration 10.0(8.8) years) were assessed by clinical, laboratory, and ultrasound examinations. Frozen plasma samples (−80 °C) were analysed for calprotectin levels at baseline, 1, 2, 3, 6 and 12 months by use of either enzyme-linked immunosorbent assay (ELISA) or fluoroenzyme immunoassay (FEIA). The ELISA technique used kits from Calpro AS and the FEIA technology was assessed on an automated Thermo Fisher Scientific instrument. The results showed high correlations between the two methods at baseline and during follow-up, with Spearman correlation at baseline 0.93 (p < 0.001) in the early and 0.96 (p < 0.001) in the established RA cohorts. The correlations between each of the two calprotectin assessments and clinical examinations had similar range. Calprotectin correlated well with clinical examinations, with at least as high correlations as CRP and ESR. The present study showed similar results for the two analytical methods, supporting the robustness of calprotectin analyses, and suggest calprotectin in plasma to be included in the assessments offered by clinical routine laboratories.

• Bjørlykke, Kristin H.; Ørbo, Hilde Sofie Sager; Tveter, Anne Therese; Jyssum, Ingrid; Sexton, Joseph & Tran, Trung [Show all 21 contributors for this article] (2022). Four SARS-CoV-2 vaccine doses or hybrid immunity in patients on immunosuppressive therapies: a Norwegian cohort study. The Lancet Rheumatology. 5(1), p. e36–e46. doi: 10.1016/S2665-9913(22)00330-7. Full text in Research Archive Show summary

  Background Data on response and safety of repeated vaccinations and hybrid immunity in patients with immune-mediated inflammatory diseases on immunosuppressive therapy is needed to further develop vaccination strategies in this vulnerable population. This study aimed to evaluate hybrid immunity and humoral immune response and safety of four SARS-CoV-2 vaccine doses in patients with immune-mediated inflammatory diseases on immunosuppressive therapy. Methods This prospective observational Norwegian study of vaccine response to COVID-19 (Nor-vaC) included adult patients aged 18 years and older with immune-mediated inflammatory diseases (rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, Crohn's disease, or ulcerative colitis) on immunosuppressive therapy, who had received four SARS-CoV-2 vaccine doses (vaccine group) or three vaccine doses followed by COVID-19 (hybrid group), and healthy controls receiving three vaccine doses (control group). Patients were recruited from the Division of Rheumatology at Diakonhjemmet Hospital, Oslo, and the Department of Gastroenterology at Akershus University Hospital, Lørenskog. Patients who had COVID-19 before the third vaccine dose, and patients with allergies or intolerances to elements of the vaccine were excluded. Antibodies to the receptor-binding domain of SARS-CoV-2 spike protein (anti-RBD antibodies) were assessed 2–4 weeks following vaccination or COVID-19. This study is registered at Clinialtrials.gov, NCT04798625. Findings Between Nov 12, 2021, and April 19, 2022, 1458 participants with immune-mediated inflammatory diseases provided post-vaccination samples at 2–4 weeks following a third vaccine dose. After 544 participants were excluded, 715 (78%) of the remaining 914 participants received the fourth dose of the vaccine, and of these, 536 (75%) provided post-vaccination samples 2–4 weeks after their fourth vaccination (vaccine group). 199 (22%) of the 914 had COVID-19 after their third dose of the vaccine and of these, 167 (84%) provided samples (hybrid group). 256 of the eligible 703 patients had rheumatoid arthritis, 107 had spondyloarthritis, 115 had psoriatic arthritis, 130 had Crohn's disease, and 95 had ulcerative colitis). Median age was 56 years [IQR 45–65], 398 (57%) were women, and 305 (43%) were men. Patients in the vaccine group had higher anti-RBD antibody concentrations following the fourth vaccine dose (median 6192 BAU/ml [IQR 2878–11 243]) than after the third dose (median 5087 BAU/ml [1250–9081]; p< 0·0001), but lower antibody concentrations than the control group following the third dose (median 7595 BAU/ml [5916–12 001]; p< 0·0001). Antibody concentrations were higher in the patients in the hybrid group (23 548 BAU/ml [IQR 11 440–35 935]) than in the vaccine group (p<0·0001). No difference was found in antibody concentrations between the fourth dose of BNT162b2 (full-dose) and mRNA-1273 (half-dose). Patients and controls had a comparable safety profile after both three and four vaccine doses. Interpretation Vaccine boosters improve humoral immune responses and are safe in patients with immune-mediated inflammatory diseases on immunosuppressive therapy, and administration should be considered regularly in this patient group. Hybrid immunity with omicron induces a strong humoral response suggesting longer intervals between booster doses in this patient group.

• Tønnessen, Theis Christian; Melleby, Arne Olav; Hauge-Iversen, Ida Marie; Espe, Emil Knut Stenersen; Ahmed, Muhammad Shakil & Ueland, Thor [Show all 12 contributors for this article] (2022). Impact of delayed type hypersensitivity arthritis on development of heart failure by aortic constriction in mice. PLOS ONE. 17(1). doi: 10.1371/journal.pone.0262821. Full text in Research Archive Show summary

  Aims Patients with rheumatoid arthritis (RA) have increased risk of heart failure (HF). The mechanisms and cardiac prerequisites explaining this association remain unresolved. In this study, we sought to determine the potential cardiac impact of an experimental model of RA in mice subjected to HF by constriction of the ascending aorta. Methods Aorta was constricted via thoracotomy and placement of o-rings with inner diameter 0.55 mm or 0.66 mm, or sham operated. RA-like phenotype was instigated by delayed-type hypersensitivity arthritis (DTHA) two weeks after surgery and re-iterated after additional 18 days. Cardiac magnetic resonance imaging (MRI) was performed before surgery and at successive time points throughout the study. Six weeks after surgery the mice were euthanized, blood and tissue were collected, organ weights were documented, and expression levels of cardiac foetal genes were analysed. In a supplemental study, DTHA-mice were euthanized throughout 14 days after induction of arthritis, and blood was analysed for important markers and mediators of RA (SAP, TNF-α and IL-6). In order to put the latter findings into clinical context, the same molecules were analysed in serum from untreated RA patients and compared to healthy controls. Results Significant elevations of inflammatory markers were found in both patient- and murine blood. Furthermore, the DTHA model appeared clinically relevant when compared to the inflammatory responses observed in three prespecified RA severity disease states. Two distinct trajectories of cardiac dysfunction and HF development were found using the two o-ring sizes. These differences were consistent by both MRI, organ weights and cardiac foetal gene expression levels. Still, no difference within the HF groups, nor within the sham groups, could be found when DTHA was induced. Conclusion DTHA mediated systemic inflammation did not cause, nor modify HF caused by aortic constriction. This indicates other prerequisites for RA-induced cardiac dysfunction.

• Norvang, Vibeke; Haavardsholm, Espen A.; Tedeschi, Sara K.; Lyu, Houchen; Sexton, Joseph & Mjaavatten, Maria Dahl [Show all 9 contributors for this article] (2022). Using observational study data as an external control group for a clinical trial: an empirical comparison of methods to account for longitudinal missing data. BMC Medical Research Methodology. 22(152), p. 1–10. doi: 10.1186/s12874-022-01639-0. Full text in Research Archive Show summary

  Background Observational data are increasingly being used to conduct external comparisons to clinical trials. In this study, we empirically examined whether different methodological approaches to longitudinal missing data affected study conclusions in this setting. Methods We used data from one clinical trial and one prospective observational study, both Norwegian multicenter studies including patients with recently diagnosed rheumatoid arthritis and implementing similar treatment strategies, but with different stringency. A binary disease remission status was defined at 6, 12, and 24 months in both studies. After identifying patterns of longitudinal missing outcome data, we evaluated the following five approaches to handle missingness: analyses of patients with complete follow-up data, multiple imputation (MI), inverse probability of censoring weighting (IPCW), and two combinations of MI and IPCW. Results We found a complex non-monotone missing data pattern in the observational study (N = 328), while missing data in the trial (N = 188) was monotone due to drop-out. In the observational study, only 39.0% of patients had complete outcome data, compared to 89.9% in the trial. All approaches to missing data indicated favorable outcomes of the treatment strategy in the trial and resulted in similar study conclusions. Variations in results across approaches were mainly due to variations in estimated outcomes for the observational data. Conclusions Five different approaches to handle longitudinal missing data resulted in similar conclusions in our example. However, the extent and complexity of missing observational data affected estimated comparative outcomes across approaches, highlighting the need for careful consideration of methods to account for missingness in this setting. Based on this empirical examination, we recommend using a prespecified advanced missing data approach to account for longitudinal missing data, and to conduct alternative approaches in sensitivity analyses.

• Brun, Marthe Kirkesæther; Goll, Guro Løvik; Jørgensen, Kristin Kaasen; Sexton, Joseph; Gehin, Johanna Elin & Sandanger, Øystein [Show all 15 contributors for this article] (2022). Risk factors for anti-drug antibody formation to infliximab: Secondary analyses of a randomised controlled trial. Journal of Internal Medicine. ISSN 0954-6820. 292(3), p. 477–491. doi: 10.1111/joim.13495. Full text in Research Archive Show summary

  Background Anti-drug antibodies (ADAb) frequently form early in the treatment course of infliximab and other tumour necrosis factor (TNF) inhibitors, leading to treatment failure and adverse events. Objective To identify risk factors for ADAb in the early phase of infliximab treatment. Methods Patients (n = 410) with immune-mediated inflammatory diseases who initiated infliximab treatment were included in the 38-week Norwegian Drug Monitoring Trial (NOR-DRUM) A and randomised 1:1 to therapeutic drug monitoring (TDM) or standard therapy. Serum levels of infliximab and ADAb were measured at each infusion. Possible risk factors for ADAb formation were assessed using logistic regression, adjusting for potential confounders. Results ADAb were detected in 78 (19%) patients. A diagnosis of rheumatoid arthritis (RA) (odds ratio [OR], 1.9 [95% confidence interval [CI] 1.0–3.6]) and lifetime smoking (OR, 2.0 [CI 1.1–3.6]) were baseline risk factors, while baseline use of concomitant immunosuppressors (OR, 0.4 [CI 0.2–0.8]) and a diagnosis of spondyloarthritis (SpA) (OR, 0.4 [CI 0.2–0.8]) reduced the risk of ADAb. Higher disease activity during follow-up (OR, 1.1 [CI 1.0–1.1]) and “drug holidays” of more than 11 weeks (OR, 4.1 [CI 1.2–13.8]) increased the risk of ADAb, whereas higher infliximab doses (OR, 0.1 [CI 0.0–0.3) and higher serum infliximab concentrations (OR, 0.7 [CI 0.6–0.8]) reduced the risk of immunogenicity. Conclusion Several risk factors for ADAb formation during early-phase infliximab treatment were identified. This knowledge provides a basis for treatment strategies to mitigate the formation of ADAb and identify patients in whom these measures are of particular importance.

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• Vikse, Jens; Haavardsholm, Espen A. & Molberg, Øyvind (2024). Revmatologi. Universitetsforlaget. ISBN 9788215068589. 400 p. Full text in Research Archive

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• Østerås, Nina; Haavardsholm, Espen A.; Mæhlen, Marthe Thoresen; Andersson, Helena & Goll, Guro Løvik (2026). Panelsamtale - Hva inspirerte deg på årets EULAR? doi: https:/www.diakonhjemmetsykehus.no/49d70f/contentassets/dd1c5c9a796d4c4ca72e0ebe655d8545/program-gronn-kongress-2026.pdf. Full text in Research Archive
• Haavardsholm, Espen A. (2026). Får Gleditschprisen 2026. [Journal]. Dagens Medisin. Full text in Research Archive Show summary

  Professor og forskningssjef Espen A. Haavardsholm tildeles Gleditschprisen 2026.

• Haavardsholm, Espen A. & Bergsmark, Kjetil (2026). Diakonhjemmet sykehus ønsker flere industristudier - NorTrials. Full text in Research Archive Show summary

  - Vi rigger oss til å bli et studieklart sykehus, og ønsker oss flere industristudier, sier administrerende direktør Kari-Jussie Lønning.

• Hagen, Gunhild; Syversen, Silje & Haavardsholm, Espen A. (2026). Skreddersydd infliksimab-behandling kan spare 5772 kroner per pasient – Legemiddelindustrien. [Internet]. LMI - Legemiddelindustrien. Full text in Research Archive Show summary

  Pasienter med revmatiske sykdommer, tarmsykdommer og hudsykdommer som får infliksimab-dosen tilpasset etter blodprøver, opplever færre sykdomsoppbluss – og helsetjenesten sparer penger. Det viser nye analyser fra NOR-DRUM-studien ved Diakonhjemmet sykehus, skriver HealthTalk.

• Hagen, Gunhild; Syversen, Silje & Haavardsholm, Espen A. (2026). Skreddersydd infliksimab-behandling gir færre oppbluss og sparer 5772 kroner per pasient. [Journal]. Health Talk. Full text in Research Archive Show summary

  Tilpasset infliksimab-behandling med terapeutisk legemiddelmonitorering gir færre sykdomsoppbluss og lavere ressursbruk, viser NOR-DRUM-studien ved Diakonhjemmet sykehus. Helseøkonomiske analyser anslår en besparelse på 5772 kroner per pasient i året.

• Berg, Inger Jorid; Asphaug, Lars; Kristianslund, Eirik; Tveter, Anne Therese; Gossec, Laure & Macfarlane, Gary J [Show all 12 contributors for this article] (2026). Patient-initiated follow-up is more cost-effective than remote monitoring or usual care in axial spondyloarthritis, results from the ReMonit randomized controlled trial. Full text in Research Archive
• Hetlevik, Siri Opsahl; Lilleby, Vibke; Pesonen, Maiju; Nordal, Ellen Berit; Rygg, Marite & Austad, Cathrine [Show all 17 contributors for this article] (2026). Moving towards optimized treatment for children and adolescents with juvenile idiopathic arthritis in sustained remission randomized to continue stable treatment, methotrexate withdrawal or tumor necrosis factor inhibitor withdrawal: study protocol for the Norwegian multi-center MOVE-JIA trial. doi: 10.1186/s13063-026-09539-0. Full text in Research Archive
• Fatima, Tahzeeb; Zhang, Yuan; Vasileiadis, Georgios K.; Rawshani, Araz; Vollenhoven, Ronald van & Lampa, Jon [Show all 20 contributors for this article] (2025). Correction: Disease activity and treatment response in early rheumatoid arthritis: an exploratory metabolomic profiling in the NORD-STAR cohort. Arthritis Research & Therapy. ISSN 1478-6354. 27(1). doi: 10.1186/s13075-025-03657-x. Full text in Research Archive
• Herder, Ingrid; Hetlevik, Siri Opsahl; Gehin, J. E.; Pesonen, Maiju; Lilleby, Vibke & Rygg, Marite [Show all 17 contributors for this article] (2025). PT006 Adalimumab serum levels and associations with disease activity in juvenile idiopathic arthritis. Pediatric Rheumatology. 23(2). Full text in Research Archive
• Bøyesen, Pernille; Aga, Anna-Birgitte; Lilleby, Vibke; Pesonen, Maiju; Rygg, Marite & Nordal, Ellen Berit [Show all 17 contributors for this article] (2025). O09 Long-term treatment efficacy of intra-articular triamcinolone hexacetonide injections in juvenile idiopathic arthritis patients starting tumor necrosis factor inhibitor therapy: 48-week results from a randomized, phase 4 trial - the myjia trial. Pediatric Rheumatology. 23(2). Full text in Research Archive
• Haavardsholm, Espen A. (2025). Professor og forskningssjef Espen A. Haavardsholm fyller 50 år. [Journal]. Budstikka og Aftenposten NTB. Full text in Research Archive
• Vigeland, Maria Dehli; Heinicke, Fatima; Flåm, Siri Tennebø; Lillegraven, Siri; Mjaavatten, Maria Dahl & Syversen, Silje Watterdal [Show all 8 contributors for this article] (2025). ABS0248 METHOTREXATE TREATMENT CHANGES GENE EXPRESSION IN CD19+ B-CELLS FROM RHEUMATOID ARTHRITIS PATIENTS. Annals of the Rheumatic Diseases. ISSN 0003-4967. 84, p. 1950–1950. doi: 10.1016/j.ard.2025.06.1500. Full text in Research Archive
• Holly, T.; Brun, Marthe Kirkesæther; Jørgensen, K.K.; Goll, Guro Løvik; Sexton, Joseph & Gehin, Johanna [Show all 15 contributors for this article] (2025). POS1077 Cost-effectiveness of proactive terapeutic drug monitoring (TDM) in patients with inflmmatory disease-results from the Nor-Drum trial. doi: 10.1016/j.ard.2025.06.431. Full text in Research Archive
• Lillejordet, Even; Sundlisæter, Nina Paulshus; Sexton, Joseph; Fongen, Birgit Camilla; Moholt, Ellen & Ljoså, Maud-Kristine Aga [Show all 19 contributors for this article] (2025). POS1047 CLINICAL AND ULTRASOUND FEATURES IN AN INCEPTION COHORT OF TREATMENT NAÏVE PATIENTS WITH PSORIATIC ARTHRITIS. Annals of the Rheumatic Diseases. ISSN 0003-4967. 84(Supplement 1), p. 1149–1149. doi: https:/www.sciencedirect.com/science/article/pii/S0003496725024537. Full text in Research Archive Show summary

  Background: Assessing a newly diagnosed patient with psoriatic arthritis (PsA) can be challenging, and the correct evaluation of clinical features may influence treatment decisions and prognosis. Current treatment recommendations underline this, as patients are stratified based on features such as enthesitis, predominant axial disease, or predominant skin and nail disease [1]. Ultrasound can be an important clinical tool to ensure correct treatment decisions from the onset of the disease. Objectives: To describe the clinical and ultrasound characteristics of treatment naïve PsA patients starting their first disease-modifying anti-rheumatic drug, including structured assessment of disease activity in joints, entheses, skin, and nails. Methods: Patients diagnosed with PsA who fulfilled the ClASsification for Psoriatic Arthritis (CASPAR) criteria starting their first disease-modifying antirheumatic drug were included in an ongoing Norwegian multi-center study (NCT05291819). Patients underwent extensive clinical and ultrasound assessments. The clinical examination of joints included assessments of 66/68 swollen (SJC) and tender (TJC) joints and identification of dactylitis. The presence of enthesitis was evaluated clinically according to the Leeds Enthesitis Index (LEI) and the Spondyloarthritis Research Consortium of Canada (SPARCC) enthesitis scoring system. Skin- and nail involvement was assessed by psoriasis body surface area (BSA), static Physician Global Assessment of Psoriasis (sPGA), and modified Nail Psoriasis Severity Index (mNAPSI). The Disease Activity Index for Psoriatic Arthritis (DAPSA) was used to assess the disease activity, and patient-reported outcomes were collected, such as patient global assessment of disease, pain, and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). All patients underwent a comprehensive ultrasound protocol with evaluation of 74 joints, 20 tendons of the hands, and 14 entheses, all scored according to OMERACT definitions. Ultrasound inflammation was defined by power Doppler (PD) >0 in any joint, enthesis, flexor tendon sheath of the fingers, or within a peritenonitis proximal to the MCP joints. The grayscale (GS) sum score is comprised of joints, the flexor tendons of the hands, peritenonitis, and the inflammatory enthesis findings of hypoechogenicity and increased thickness. Results: A total of 111 consecutive patients were included in this analysis; 64% were male, and the mean (SD) age was 44.2 (14.0) years. 93% of the patients had a history of psoriasis, while in the remaining 7% it was present in a first-degree family member (Table 1). Physician-reported history of arthritis was the most prevalent disease feature, identified in 86% of patients. A history of axial involvement was documented in 29%, enthesitis in 30%, and nail psoriasis in 47% of patients. At the time of assessment, the median (IQR) SJC was 2 (1-4) and TJC 4 (2-8). Patient global assessment of disease activity visual analog scale (VAS) was 59 (41-70), VAS pain was 60 (40-70), and CRP 5 mg/L (2-11 mg/L), whereas the VAS physician global assessment of disease was 25 (15-40). 80% had a SJC>0. The baseline DAPSA had a median (IQR) value of 18.4 (12.5-28.3), corresponding to moderate disease activity. The skin disease among the patients was mild. Although 87% had any psoriasis plaque, the median (IQR) BSA was 2% (1-4%), sPGA score 3 (2-4), and mNAPSI score 1 (0-8). The median ultrasound GS sum score was 11 (5-22) (Table 2). When focusing solely on the GS score for joints, a GS >1 was observed in 75% of patients. The median PD sum score was 3 (0-7), with 69% having a value >0 in any of the ultrasound-examined structures. 52% had any joint with PD>0. A PD-signal >0 was observed in an enthesis in 35% of the patients, with the lateral epicondyle being the most commonly affected enthesis (12%), followed by the proximal patellar tendon insertion (11%). Additionally, peritenonitis was identified in 19%, and flexor tenosynovitis in 21%. Conclusion: In this treatment naïve early PsA inception cohort with an aim to include all PsA patients starting DMARD treatment, extensive examinations illustrated the heterogeneous nature of the disease. After skin psoriasis, arthritis was the feature affecting most patients, with clinically swollen joints in 80% and ultrasound PD joint synovitis in 52%. Other aspects of PsA, such as a clinical finding of dactylitis and ultrasound findings of enthesitis, tenosynovitis, and peritenonitis, each had an overall prevalence of at least 20%, reflecting the diversity of this patient population. Ultrasound might add useful information about inflammation in a number of structures. In conclusion, extensive examination of affected structures is necessary to guide treatment decisions in early PsA.

• Holly, Teresa; Brun, Marthe Kirkesæther; Jørgensen, Kristin Kaasen; Goll, Guro Løvik; Sexton, Joseph & Gehin, Johanna [Show all 16 contributors for this article] (2025). Cost-effectiveness of proactive therapeutic drug monitoring (TDM) in patients with inflmmatory disease-results from the Nor-Drum trial. Full text in Research Archive
• Hagen, Gunhild; Arif, Sonia; Karoliussen, Lars Fridtjof; Sexton, Joseph; Haavardsholm, Espen Andre & Provan, Sella Aarrestad [Show all 8 contributors for this article] (2025). Treating gout to target serum urate improves health-related quality of life and utility over five years. Full text in Research Archive
• Kjørholt, Kaja Eriksrud; Sundlisæter, Nina Paulshus; Haavardsholm, Espen A. & Lillegraven, Siri (2024). Norsk leddgikt-studie: Overraskende funn om medisiner. [Journal]. VG papirutgave. Full text in Research Archive
• Helsingen, Lise Mørkved; Langeland, Eline Aurvoll; Pisani, Synne Eline Rotihaug; Vandvik, Per Olav; Haavardsholm, Espen A. & Malt, Ulrik Fredrik [Show all 10 contributors for this article] (2024). Glansbilder av nasjonale faglige retningslinjer fra Helsedirektoratet. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 144(5). doi: 10.4045/tidsskr.24.0141. Full text in Research Archive
• Vikse, Jens; Mjaavatten, Maria Dahl & Haavardsholm, Espen A. (2024). Reaktiv artritt. In Vikse, Jens; Haavardsholm, Espen A. & Molberg, Øyvind (Ed.), Revmatologi. Universitetsforlaget. ISSN 9788215068589. p. 211–212. Full text in Research Archive
• Vikse, Jens; Lillejordet, Even; Fagerli, Karen Minde; Bakland, Gunnstein & Haavardsholm, Espen A. (2024). Spondyloartritt: en oversikt. In Vikse, Jens; Haavardsholm, Espen A. & Molberg, Øyvind (Ed.), Revmatologi. Universitetsforlaget. ISSN 9788215068589. p. 190–201. Full text in Research Archive
• Vikse, Jens; Hammer, Hilde Berner; Nystad, Tone Wikene; Uhlig, Till & Haavardsholm, Espen A. (2024). Urinsyregikt. In Vikse, Jens; Haavardsholm, Espen A. & Molberg, Øyvind (Ed.), Revmatologi. Universitetsforlaget. ISSN 9788215068589. p. 216–228. Full text in Research Archive
• Vikse, Jens; Hammer, Hilde Berner; Bader, Lucius & Haavardsholm, Espen A. (2024). Leddsmerter. In Vikse, Jens; Haavardsholm, Espen A. & Molberg, Øyvind (Ed.), Revmatologi. Universitetsforlaget. ISSN 9788215068589. Full text in Research Archive
• Vikse, Jens; Bakland, Gunnstein; Berg, Inger Jorid & Haavardsholm, Espen A. (2024). Aksial spondyloartritt. In Vikse, Jens; Haavardsholm, Espen A. & Molberg, Øyvind (Ed.), Revmatologi. Universitetsforlaget. ISSN 9788215068589. p. 202–206. Full text in Research Archive
• Vikse, Jens; Fevang, Bjørg Tilde Svanes & Haavardsholm, Espen A. (2024). Artrittsykdommer: en oversikt. In Vikse, Jens; Haavardsholm, Espen A. & Molberg, Øyvind (Ed.), Revmatologi. Universitetsforlaget. ISSN 9788215068589. Full text in Research Archive
• Vikse, Jens; Bader, Lucius; Goll, Guro Løvik; Molberg, Øyvind & Haavardsholm, Espen A. (2024). Immunsupprimerende behandling. In Vikse, Jens; Haavardsholm, Espen A. & Molberg, Øyvind (Ed.), Revmatologi. Universitetsforlaget. ISSN 9788215068589. Full text in Research Archive
• Vikse, Jens; Hammer, Hilde Berner; Nystad, Tone Wikene; Uhlig, Till & Haavardsholm, Espen A. (2024). Krystallartritt: en oversikt. In Vikse, Jens; Haavardsholm, Espen A. & Molberg, Øyvind (Ed.), Revmatologi. Universitetsforlaget. ISSN 9788215068589. p. 213–215. Full text in Research Archive
• Vikse, Jens; Haavardsholm, Erik; Lillejordet, Even; Aaløkken, Trond Mogens; Hammer, Hilde Berner & Diamantopoulos, Andreas P [Show all 8 contributors for this article] (2024). Bildeundersøkelser. In Vikse, Jens; Haavardsholm, Espen A. & Molberg, Øyvind (Ed.), Revmatologi. Universitetsforlaget. ISSN 9788215068589. Full text in Research Archive
• Vikse, Jens; Aga, Anna-Birgitte; Fevang, Bjørg Tilde Svanes & Haavardsholm, Espen A. (2024). Revmatoid artritt. In Vikse, Jens; Haavardsholm, Espen A. & Molberg, Øyvind (Ed.), Revmatologi. Universitetsforlaget. ISSN 9788215068589. p. 180–189. Full text in Research Archive
• Vikse, Jens; Fagerli, Karen Minde; Lillejordet, Even; Madland, Tor Magne & Haavardsholm, Espen A. (2024). Psoriasisartritt. In Vikse, Jens; Haavardsholm, Espen A. & Molberg, Øyvind (Ed.), Revmatologi. Universitetsforlaget. ISSN 9788215068589. p. 207–210. Full text in Research Archive
• Kjørholt, Kaja Eriksrud; Sundlisæter, Nina Beate Paulshus; Aga, Anna-Birgitte; Sexton, Joseph; Olsen, Inge Christoffer & Madland, Tor Magne [Show all 21 contributors for this article] (2024). OP0021 3-YEAR RESULTS OF TAPERING TNFi TO WITHDRAWAL COMPARED TO STABLE TNFi AMONG RHEUMATOID ARTHRITIS PATIENTS IN SUSTAINED REMISSION: A MULTICENTER RANDOMIZED TRIAL. Annals of the Rheumatic Diseases. ISSN 0003-4967. 83, p. 188–189. doi: 10.1136/annrheumdis-2024-eular.299. Full text in Research Archive
• Heiberg, Marte Schrumpf; Kisten, Yogan; Kazemi, Amirhossein; Rezaei, Hamed; Klint, Erik af & Ljoså, Maud-Kristine Aga [Show all 26 contributors for this article] (2024). POS0474 ULTRASOUND REMISSION RATES AFTER 1 YEAR ARE HIGH IN EARLY RA PATIENTS ON INDUCTION TREATMENT: RESULTS FROM THE RANDOMIZED NORD-STAR TRIAL. Annals of the Rheumatic Diseases. ISSN 0003-4967. 83, p. 839–840. doi: 10.1136/annrheumdis-2024-eular.5080. Full text in Research Archive
• Vikse, Jens; Hammer, Hilde Berner; Nystad, Tone Wikene; Uhlig, Till & Haavardsholm, Espen A. (2024). Kalsiumpyrofosfatartritt. In Vikse, Jens; Haavardsholm, Espen A. & Molberg, Øyvind (Ed.), Revmatologi. Universitetsforlaget. ISSN 9788215068589. p. 229–230. Full text in Research Archive
• Vikse, Jens; Fevang, Bjørg Tilde Svanes; Haugeberg, Glenn; Bitter, Helle; Haavardsholm, Espen A. & Molberg, Øyvind (2024). Revmatologi: en oversikt. In Vikse, Jens; Haavardsholm, Espen A. & Molberg, Øyvind (Ed.), Revmatologi. Universitetsforlaget. ISSN 9788215068589. Full text in Research Archive
• Vikse, Jens; Schrumpf, Marte & Haavardsholm, Espen A. (2024). Revmatologi og malignitet. In Vikse, Jens; Haavardsholm, Espen A. & Molberg, Øyvind (Ed.), Revmatologi. Universitetsforlaget. ISSN 9788215068589. p. 367–370. Full text in Research Archive
• Vikse, Jens; Wallenius, Marianne; Skorpen, Carina Götestam & Haavardsholm, Espen A. (2024). Svangerskap og revmatisk sykdom. In Vikse, Jens; Haavardsholm, Espen A. & Molberg, Øyvind (Ed.), Revmatologi. Universitetsforlaget. ISSN 9788215068589. p. 373–377. Full text in Research Archive
• Vikse, Jens; bos-haugen, ida & Haavardsholm, Espen A. (2024). Artrose. In Vikse, Jens; Haavardsholm, Espen A. & Molberg, Øyvind (Ed.), Revmatologi. Universitetsforlaget. ISSN 9788215068589. p. 236–240. Full text in Research Archive
• Vikse, Jens; Salte, Tore; Dale, Håvard; Nystad, Tone Wikene; Syversen, Silje Watterdal & Karoliussen, Lars Fridtjof [Show all 9 contributors for this article] (2024). Infeksiøs artritt. In Vikse, Jens; Haavardsholm, Espen A. & Molberg, Øyvind (Ed.), Revmatologi. Universitetsforlaget. ISSN 9788215068589. Full text in Research Archive
• Moe, Rikke Helene; Haavardsholm, Espen A.; Lillegraven, Siri & semb, anne grete (2023). To av tre kan bli symptomfrie. [Journal]. VG online og papirutgave. Full text in Research Archive
• Melokhina, Valeriia; Sundlisæter, Nina Paulshus; Sexton, Joseph; Sundin, Ulf Gunnar; Aga, Anna-Birgitte & Kjørholt, Kaja Eriksrud [Show all 10 contributors for this article] (2023). Subclinical inflammation and joint damage progression in patients with early RA fulfilling 2011 vs 2022 ACR/EULAR Boolean remission criteria: Data from the ARCTIC study. Annals of the Rheumatic Diseases. ISSN 0003-4967. doi: 10.1136/ard-2023-224950. Full text in Research Archive
• Syversen, Silje Watterdal; Gehin, Johanna; Goll, Guro Løvik; Bolstad, Nils; Haavardsholm, Espen A. & Bakke, Emilie Andrea [Show all 7 contributors for this article] (2023). Therapeutic Drug Monitoring: A Tool to Optimize Treatment of Inflammatory Joint Diseases. Arthritis & Rheumatology. ISSN 2326-5191. doi: 10.1002/art.42764. Full text in Research Archive
• Haavardsholm, Espen A. & Lillegraven, Siri (2023). Brukermedvirkning kan gi bedre forskning. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 143(9). doi: 10.4045/tidsskr.23.0245. Full text in Research Archive
• Haavardsholm, Espen A. (2023). Er retningslinjene fra Helsedirektoratet til å stole på? Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 143(14). doi: 10.4045/tidsskr.23.0622. Full text in Research Archive
• Haavardsholm, Espen A. (2023). Norsk ekspert: Dette er de viktigste nyhetene innen behandling av leddgikt. [Internet]. HealthTalk. Full text in Research Archive
• Østergaard, Mikkel; Vollenhoven, Ronald van; Rudin, Anna; Hetland, Merete L.; Schrumpf, Marte & Nordström, Dan [Show all 44 contributors for this article] (2022). CERTOLIZUMAB-PEGOL, ABATACEPT, TOCILIZUMAB OR ACTIVE CONVENTIONAL THERAPY IN EARLY RHEUMATOID ARTHRITIS: CLINICAL AND RADIOGRAPHIC 48-WEEKS RESULTS OF THE INVESTIGATOR-INITIATED RANDOMIZED NORD-STAR TRIAL. Annals of the Rheumatic Diseases. ISSN 0003-4967. 81, p. 38–40. Full text in Research Archive
• Syversen, Silje Watterdal; Jahnsen, Jørgen & Haavardsholm, Espen A. (2022). Therapeutic Drug Monitoring vs Standard Therapy During Maintenance Infliximab Therapy and Control of Immune-Mediated Inflammatory Diseases-Reply. Journal of the American Medical Association (JAMA). ISSN 0098-7484. 327(15), p. 1506–1507. doi: 10.1001/jama.2022.2938. Full text in Research Archive

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