Kristin Kaasen Jørgensen

• Rasmussen, Tilde Harridsleff; Schikora-Rustad, Stine; Lorentzen, Åslaug Rudjord; Tran, Trung; Øverås, Mathias Herstad & Myhr, Kjell-Morten [Show all 22 contributors for this article] (2026). Low risk of severe COVID-19 in vaccinated people with multiple sclerosis: a nationwide Norwegian study. BMJ Neurology Open. 8(1). doi: 10.1136/bmjno-2026-001556. Full text in Research Archive Show summary

  Background: We aimed to assess antibody responses and COVID-19 outcomes after vaccination in people with multiple sclerosis (pwMS) receiving disease-modifying therapies. Methods: NevroVAX is a Norwegian multicentre cohort study including 3559 pwMS and 449 healthy controls (HCs) who received at least one dose of BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna) or ChAdOx1 (AstraZeneca/Oxford) between January 2021 and December 2022. Data from records, registries, questionnaires and blood samples collected June 2021–November 2023 were analysed. Primary outcomes were humoral immune responses assessed by seroconversion (anti-spike and anti-receptor-binding domain (RBD) IgG ≥5 binding antibody units/mL). Secondary outcomes included quantitative anti-RBD IgG levels, breakthrough SARS-CoV-2 infection, COVID-19-related hospitalisation and death. Associations with breakthrough infection were evaluated using multivariable logistic regression. Results: Among 3559 pwMS, 1201 received anti-CD20 monoclonal antibodies and 324 sphingosine-1-phosphate receptor (S1PR) modulators. After three vaccine doses, seroconversion was observed in 43.0% of anti-CD20-treated patients and 48.4% of S1PR-treated patients. In multivariable analysis, seroconversion was associated with lower risk of breakthrough infection (OR 0.67, 95% CI 0.58 to 0.78). During follow-up, 58 pwMS (1.6%) were hospitalised for COVID-19; 4 (0.1%) required non-invasive ventilatory support, no patients required invasive ventilation and no deaths occurred. Conclusions: Humoral vaccine responses were impaired in pwMS receiving anti-CD20 or S1PR therapies, but severe COVID-19 was rare. These findings support continued vaccination programmes and tailored protective measures for immunomodulated populations.

• 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
• Bajer, Lukas; Polakovicova, Petra; Heczkova, Marie; Holm, Kristian; Hole, Mikal Jacob & Hlavaty, Mojmir [Show all 19 contributors for this article] (2025). Geography-independent mucosal microbiota alterations in primary sclerosing cholangitis persist after liver transplantation. JHEP Reports. 8(4). doi: 10.1016/j.jhepr.2025.101716. Full text in Research Archive Show summary

  Background & Aims Primary sclerosing cholangitis (PSC)-associated alterations of fecal gut microbiota have already been described, but data on the mucosal microbiota are still limited. We aimed to further define disease-specific mucosal microbial patterns independent of geography and assess the relationship to liver transplantation (LTx), gut inflammation (inflammatory bowel disease), and PSC recurrence (rPSC). Methods We performed 16S ribosomal RNA gene (V3–V4) sequencing of ileocolonic biopsies from 115 patients with PSC (pre-LTx), 159 liver-transplanted patients (post_LTx, recurrence occurred in 38), and 96 healthy controls (HC) from Norway and the Czech Republic. Results Alpha diversity was lower in all PSC groups compared with HC. Elastic net models discriminated pre_LTx (AUC ileum 0.97; colon 0.93; p <0.001) and post_LTx PSC patients (AUC ileum 0.97; colon 0.97; p <0.001) from HC, and distinguished pre_LTx from post_LTx (AUC ileum 0.83; colon 0.83; p <0.001). The shared, cohort-independent PSC microbiota was dominated by Enterococcus, Pseudomonas, Veillonella, Klebsiella, and Streptococcus, while several common commensals were underrepresented. A microbial dysbiosis index calculated from PSC-associated genera correlated negatively with alpha diversity and serum albumin, while a positive correlation was observed with markers of cholestatic disease (ALP, GGT) and liver fibrosis (APRI). There were no associations with the presence of inflammatory bowel disease or fecal calprotectin. Differences between post-LTx patients with and without recurrence were limited, but several genera deregulated in pre-LTx PSC (Klebsiella, Bilophila, Coprococcus, Odoribacter) showed similar trends in rPSC. Conclusions Our findings in two European countries revealed a distinct mucosal microbiota composition associated with PSC that persists after LTx. These microbial patterns correlate with the severity of liver injury in PSC but not with markers of intestinal inflammation. Impact and implications This study provides an extensive evaluation of mucosa-associated microbiota in primary sclerosing cholangitis (PSC) before and after liver transplantation across two European cohorts. The persistence of PSC-related dysbiosis after transplantation highlights the importance of the gut–liver axis in PSC and supports further investigation into microbiota-driven mechanisms. Together with the strong association between microbiota composition and markers of cholestasis and fibrosis, this suggests potential clinical utility as an indicator of disease activity or even as a target for prevention or therapy.

• Mol, Bregje; Nieuwamerongen, Moyrha van; Munster, Kim N. van; Färkkilä, Martti; Folseraas, Trine & Tjønnfjord, Sara Kristina Viberg [Show all 19 contributors for this article] (2025). Proctocolectomy with permanent ileostomy is associated with improved transplant-free survival in patients with PSC. JHEP Reports. 8(3). doi: 10.1016/j.jhepr.2025.101700. Full text in Research Archive Show summary

  Background & Aims The gut–liver axis is believed to be crucial in the pathogenesis of primary sclerosing cholangitis (PSC). However, the impact of colectomy on liver disease progression is unclear. Our study estimated the effect of colectomy on PSC progression with correction for time dependency and established risk factors by pooling data from several cohorts across different countries. Methods We analysed data from the International PSC Registry (IPSCR), comprising patients from Finland, The Netherlands, Norway, and Sweden. Primary endpoint was defined as liver transplantation (LT) or PSC-related death. Cox proportional hazards regression onto time-dependent colectomy status, with specification for extent, was performed with adjustment for sex, age at diagnosis, large or small duct PSC, features of autoimmune hepatitis, time-dependent inflammatory bowel disease (IBD) status, centre of inclusion, and country of residence. Results A total of 3,110 participants were included, of whom 470 (15%) had undergone colectomy. During a total follow-up of 32,236 patient-years, 395 deaths and 653 LTs were observed. Compared with patients with PSC with intact colon, the hazard ratio (HR) of reaching LT or PSC-related death was significantly decreased in patients with proctocolectomy with permanent ileostomy (HR 0.41; 95% CI 0.24–0.71). This effect was less pronounced in case of hemi- or subtotal colectomy (HR 0.81; 95% CI: 0.58–1.12) and not observed for proctocolectomy with pouch (HR 1.00; 95% CI: 0.73–1.38). The reduced risk was mainly associated with a lower rate of LT or death resulting from liver failure (HR 0.24; 0.10–0.53). Conclusions Proctocolectomy with permanent ileostomy was associated with decreased risk for LT and PSC-related death. These findings support the role of the gut–liver axis in the pathophysiology of PSC and call for consideration in counselling patients who face impending colorectal surgery. Impact and implications The impact of the gut-liver axis in the pathophysiology of primary sclerosing cholangitis (PSC) has remained uncertain. In this study, proctocolectomy with ileostomy was associated with improved transplant-free survival, defined as a reduced risk of liver transplantation or PSC-related death, indicating that intestinal factors may influence disease progression. These findings are important for clinicians, researchers, and patients as they suggest that surgical management of colonic disease may have prognostic implications in PSC, and for further studies to clarify mechanisms and guide clinical decision-making.

• Singh, Yashbir; Eaton, John E.; Venkatesh, Sudhakar K.; Welle, Christopher L.; Smith, Byron & Faghani, Shahriar [Show all 24 contributors for this article] (2025). Deep learning analysis of MRI accurately detects early-stage perihilar cholangiocarcinoma in patients with primary sclerosing cholangitis. Hepatology. ISSN 0270-9139. 83(1), p. 30–39. doi: 10.1097/HEP.0000000000001314. Full text in Research Archive
• Karlsen, Tom Hemming; Jørgensen, Kristin Kaasen & Bergquist, Annika (2024). Medical treatment of Primary Sclerosing Cholangitis: what have we learned and where are we going? Hepatology. ISSN 0270-9139. doi: 10.1097/HEP.0000000000001172. Full text in Research Archive Show summary

  It has proven difficult to establish robust evidence for significant clinical benefits of medical treatment in primary sclerosing cholangitis (PSC). For ursodeoxycholic acid, clinical practice guidelines only offer vague recommendations, leading to a situation of variable prescription rates depending on local reimbursement policies and physician preference. The difficulty in drug development in PSC is partly related to a poor understanding of critical disease processes with failure to identify relevant mechanisms of action of putative drugs. The variable disease course, both intra-individually and between individuals, and the lack of robust definitions of what success looks like for clinical trials in PSC have also contributed to the negative outcomes of trials performed. In this review article, we will discuss these uncertainties and challenges, building on key previous and ongoing clinical trials. Despite the lack of consensus for ideal phase II and phase III study designs, several trials for diverse compounds are currently ongoing, indicating a shift from therapeutic nihilism toward hope for people with PSC. While waiting for robust efficacy data for drugs currently being tested, the current lack of effective interventions should not motivate the prescription of compounds to people with PSC based on low-quality evidence.

• 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.

• Alirezaylavasani, Amin; Egner, Ingrid Marie; Dahl, Tuva Børresdatter; Chopra, Adity; Kasahara, Taissa de Matos & Goll, Guro Løvik [Show all 15 contributors for this article] (2024). Deficient SARS-CoV-2 hybrid immunity during inflammatory bowel disease. Clinical Immunology. ISSN 1521-6616. 271, p. 1–13. doi: 10.1016/j.clim.2024.110404. Full text in Research Archive Show summary

  Patients with Inflammatory Bowel Disease (IBD) undergoing immunosuppressive therapies face heightened susceptibility to severe COVID-19. An in-depth understanding of systemic inflammation and cellular immune responses after SARS-CoV-2 vaccination and breakthrough infections (BTI) is required for optimizing vaccine strategies in this population. While the prevalence of high serological responders post- third COVID-19 vaccine dose was lower, and the antibody waning was higher in IBD patients than in healthy donors (HD), IBD patients showed an increase in anti-RBD Wild Type IgG levels and cross-reactive Spike -specific memory B cells following BTI. However, there was no significant enhancement in cellular immune responses against anti-SARS-CoV-2 post-BTI, with responses instead characterized by activation of SARS-CoV-2 specific and also bystander CD8 T cells. These results suggest a complex interaction between chronic inflammation in IBD and the generation of new immune responses, highlighting the need for tailored vaccine regimens and anti-inflammatory therapies to boost cellular immunity against SARS-CoV-2.

• 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.

• 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.

• 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.

• Solitano, Virginia; Facciorusso, Antonio; McGovern, Dermot P.B.; Nguyen, Tran; Colman, Ruben J. & Zou, Lily [Show all 14 contributors for this article] (2023). HLA-DQA1∗05 Genotype and Immunogenicity to Tumor Necrosis Factor-α Antagonists: A Systematic Review and Meta-analysis. Clinical Gastroenterology and Hepatology. ISSN 1542-3565. 21(12), p. 3019–3029. doi: 10.1016/j.cgh.2023.03.044. Full text in Research Archive
• Wolf, Asia-Sophia Fumika Michaela; Ravussin, Anthony; König, Marton; Øverås, Mathias Herstad; Solum, Guri & Kjønstad, Ingrid Fadum [Show all 18 contributors for this article] (2023). T cell responses to SARS-CoV-2 vaccination differ by disease-modifying therapy for multiple sclerosis. JCI Insight. 8(12), p. 1–14. doi: 10.1172/jci.insight.165111. Full text in Research Archive Show summary

  Immune responses in people with multiple sclerosis (pwMS) receiving disease-modifying therapies (DMTs) have been of significant interest throughout the COVID-19 pandemic. Lymphocyte-targeting immunotherapies, including anti-CD20 treatments and sphingosine-1-phosphate receptor (S1PR) modulators, attenuate Ab responses after vaccination. Evaluation of cellular responses after vaccination, therefore, is of particular importance in these populations. In this study, we used flow cytometry to analyze CD4 and CD8 T cell functional responses to SARS-CoV-2 spike peptides in healthy control study participants and pwMS receiving 5 different DMTs. Although pwMS receiving rituximab and fingolimod therapies had low Ab responses after both 2 and 3 vaccine doses, T cell responses in pwMS taking rituximab were preserved after a third vaccination, even when an additional dose of rituximab was administered between vaccine doses 2 and 3. PwMS taking fingolimod had low detectable T cell responses in peripheral blood. CD4 and CD8 T cell responses to SARS-CoV-2 variants of concern Delta and Omicron were lower than to the ancestral Wuhan-Hu-1 variant. Our results indicate the importance of assessing both cellular and humoral responses after vaccination and suggest that, even in the absence of robust Ab responses, vaccination can generate immune responses in pwMS.

• Jørgensen, Kristin Kaasen; Høivik, Marte Lie; Chopra, Adity; Benth, Jurate Saltyte; Ricanek, Petr & Moum, Bjørn Allan [Show all 18 contributors for this article] (2023). Humoral immune response to SARS-CoV-2 vaccination in patients with inflammatory bowel disease on immunosuppressive medication: association to serum drug levels and disease type. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 58(8), p. 874–882. doi: 10.1080/00365521.2023.2177884. Full text in Research Archive Show summary

  Objectives Immune responses following SARS-CoV-2 vaccination in patients with inflammatory bowel disease (IBD) are not well characterized. The aims of this study were to explore the serological response associated with IBD, and immunosuppressive medications including serum concentrations of biologics and thiopurine metabolites. Materials and methods This prospective, observational study included adult patients with ulcerative colitis (UC) and Crohn’s disease (CD), and healthy controls. Antibodies to the receptor-binding domain of SARS-CoV-2 spike proteins, and serum concentrations of ongoing biologic and immunomodulatory medications were assessed prior to, and 2-5 weeks after the second vaccine dose. Serologic response was defined as anti-Spike antibodies ≥70 AU/ml. Results In 958 IBD patients (380 UC, 578 CD) and 323 healthy controls, the median (Q1; Q3) anti-Spike antibody level (AU/ml) was lower in patients (618 (192; 4370)) compared to controls (3355 (896; 7849)) (p < 0.001). The antibody levels were lower in CD (439 (174; 3304)) compared to UC (1088 (251; 5975)) (p < 0.001). No associations were demonstrated between antibody levels and serum drug concentrations for TNF inhibitor (TNFi), vedolizumab and ustekinumab. Patients receiving TNFi + thiopurines with a subtherapeutic 6-thioguanine nucleotide (6-TGN) level had higher response rate (93%) compared to patients with 6-TGN within the therapeutic range (53%) (p = 0.003). A diagnosis of UC, mRNA-1273 vaccine, and other treatments than TNFi + thiopurines were associated with humoral response. Conclusions Patients with CD had an attenuated humoral response to SARS-COV-2 vaccination as compared to patients with UC. The lack of association between serum levels of biologics and serologic response indicates vaccination regardless of proximity to drug administration.

• Gui, Wenfang; Hole, Mikal Jacob; Molinaro, Antonio; Edlund, Karolina; Jørgensen, Kristin Kaasen & Su, Huan [Show all 21 contributors for this article] (2023). Colitis ameliorates cholestatic liver disease via suppression of bile acid synthesis. Nature Communications. 14(1). doi: 10.1038/s41467-023-38840-8. Full text in Research Archive Show summary

  Abstract Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by chronic inflammation and progressive fibrosis of the biliary tree. The majority of PSC patients suffer from concomitant inflammatory bowel disease (IBD), which has been suggested to promote disease development and progression. However, the molecular mechanisms by which intestinal inflammation may aggravate cholestatic liver disease remain incompletely understood. Here, we employ an IBD-PSC mouse model to investigate the impact of colitis on bile acid metabolism and cholestatic liver injury. Unexpectedly, intestinal inflammation and barrier impairment improve acute cholestatic liver injury and result in reduced liver fibrosis in a chronic colitis model. This phenotype is independent of colitis-induced alterations of microbial bile acid metabolism but mediated via hepatocellular NF-κB activation by lipopolysaccharide (LPS), which suppresses bile acid metabolism in-vitro and in-vivo. This study identifies a colitis-triggered protective circuit suppressing cholestatic liver disease and encourages multi-organ treatment strategies for PSC.

• 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.

• Bergquist, Annika; Weismüller, Tobias J.; Levy, Cynthia; Rupp, Christian; Joshi, Deepak & Nayagam, Jeremy Shanika [Show all 45 contributors for this article] (2022). Impact on follow-up strategies in patients with primary sclerosing cholangitis. Liver international (Print). ISSN 1478-3223. doi: 10.1111/liv.15286. Full text in Research Archive Show summary

  Background & Aims: Evidence for the benefit of scheduled imaging for early detection of hepatobiliary malignancies in primary sclerosing cholangitis (PSC) is limited. We aimed to compare different follow-up strategies in PSC with the hypothesis that regular imaging improves survival. Methods: We collected retrospective data from 2975 PSC patients from 27 centres. Patients were followed from the start of scheduled imaging or in case of clinical follow-up from 1 January 2000, until death or last clinical follow-up alive. The primary endpoint was all-cause mortality. Results: A broad variety of different follow-up strategies were reported. All except one centre used regular imaging, ultrasound (US) and/or magnetic resonance imaging (MRI). Two centres used scheduled endoscopic retrograde cholangiopancreatography (ERCP) in addition to imaging for surveillance purposes. The overall HR (CI95%) for death, adjusted for sex, age and start year of follow-up, was 0.61 (0.47–0.80) for scheduled imaging with and without ERCP; 0.64 (0.48–0.86) for US/MRI and 0.53 (0.37–0.75) for follow-up strategies including scheduled ERCP. The lower risk of death remained for scheduled imaging with and without ERCP after adjustment for cholangiocarcinoma (CCA) or high-grade dysplasia as a time-dependent covariate, HR 0.57 (0.44–0.75). Hepatobiliary malignancy was diagnosed in 175 (5.9%) of the patients at 7.9 years of follow-up. Asymptomatic patients (25%) with CCA had better survival if scheduled imaging had been performed. Conclusions: Follow-up strategies vary considerably across centres. Scheduled imaging was associated with improved survival. Multiple factors may contribute to this result including early tumour detection and increased endoscopic treatment of asymptomatic benign biliary strictures.

• Singh, Yashbir; Jons, William A.; Eaton, John E.; Vesterhus, Mette Nåmdal; Karlsen, Tom Hemming & Bjørk, Ida Torunn [Show all 21 contributors for this article] (2022). Algebraic topology-based machine learning using MRI predicts outcomes in primary sclerosing cholangitis. European Radiology Experimental. 6. doi: 10.1186/s41747-022-00312-x. Full text in Research Archive Show summary

  Background: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease that can lead to cirrhosis and hepatic decompensation. However, predicting future outcomes in patients with PSC is challenging. Our aim was to extract magnetic resonance imaging (MRI) features that predict the development of hepatic decompensation by applying algebraic topology-based machine learning (ML). Methods: We conducted a retrospective multicenter study among adults with large duct PSC who underwent MRI. A topological data analysis-inspired nonlinear framework was used to predict the risk of hepatic decompensation, which was motivated by algebraic topology theory-based ML. The topological representations (persistence images) were employed as input for classification to predict who developed early hepatic decompensation within one year after their baseline MRI. Results: We reviewed 590 patients; 298 were excluded due to poor image quality or inadequate liver coverage, leaving 292 potentially eligible subjects, of which 169 subjects were included in the study. We trained our model using contrast-enhanced delayed phase T1-weighted images on a single center derivation cohort consisting of 54 patients (hepatic decompensation, n = 21; no hepatic decompensation, n = 33) and a multicenter independent validation cohort of 115 individuals (hepatic decompensation, n = 31; no hepatic decompensation, n = 84). When our model was applied in the independent validation cohort, it remained predictive of early hepatic decompensation (area under the receiver operating characteristic curve = 0.84). Conclusions: Algebraic topology-based ML is a methodological approach that can predict outcomes in patients with PSC and has the potential for application in other chronic liver diseases.

• 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.

• Syversen, Silje Watterdal; Jyssum, Ingrid; Tveter, Anne Therese; Tran, Trung; Sexton, Joseph & Provan, Sella Aarrestad [Show all 22 contributors for this article] (2022). Immunogenicity and Safety of Standard and Third-Dose SARS-CoV-2 Vaccination in Patients Receiving Immunosuppressive Therapy. Arthritis & Rheumatology. ISSN 2326-5191. 74(8), p. 1321–1332. doi: 10.1002/art.42153. Full text in Research Archive Show summary

  Objective Immunogenicity and safety following receipt of the standard SARS–CoV-2 vaccination regimen in patients with immune-mediated inflammatory diseases (IMIDs) are poorly characterized, and data after receipt of the third vaccine dose are lacking. The aim of the study was to evaluate serologic responses and adverse events following the standard 2-dose regimen and a third dose of SARS–CoV-2 vaccine in IMID patients receiving immunosuppressive therapy. Methods Adult patients receiving immunosuppressive therapy for rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, Crohn's disease, or ulcerative colitis, as well as healthy adult controls, who received the standard 2-dose SARS–CoV-2 vaccination regimen were included in this prospective observational study. Analyses of antibodies to the receptor-binding domain (RBD) of the SARS–CoV-2 spike protein were performed prior to and 2–4 weeks after vaccination. Patients with a weak serologic response, defined as an IgG antibody titer of ≤100 arbitrary units per milliliter (AU/ml) against the receptor-binding domain of the full-length SARS–Cov-2 spike protein, were allotted a third vaccine dose. Results A total of 1,505 patients (91%) and 1,096 healthy controls (98%) had a serologic response to the standard regimen (P < 0.001). Anti-RBD antibody levels were lower in patients (median 619 AU/ml interquartile range [IQR] 192–4,191) than in controls (median 3,355 AU/ml [IQR 896–7,849]) (P < 0.001). The proportion of responders was lowest among patients receiving tumor necrosis factor inhibitor combination therapy, JAK inhibitors, or abatacept. Younger age and receipt of messenger RNA–1273 vaccine were predictors of serologic response. Of 153 patients who had a weak response to the standard regimen and received a third dose, 129 (84%) became responders. The vaccine safety profile among patients and controls was comparable. Conclusion IMID patients had an attenuated response to the standard vaccination regimen as compared to healthy controls. A third vaccine dose was safe and resulted in serologic response in most patients. These data facilitate identification of patient groups at risk of an attenuated vaccine response, and they support administering a third vaccine dose to IMID patients with a weak serologic response to the standard regimen.

• Hole, Mikal Jacob; Jørgensen, Kristin Kaasen; Holm, Kristian; Braadland, Peder Rustøen; Meyer-Myklestad, Malin Holm & Medhus, Asle Wilhelm [Show all 13 contributors for this article] (2022). A shared mucosal gut microbiota signature in primary sclerosing cholangitis before and after liver transplantation. Hepatology. ISSN 0270-9139. doi: 10.1002/hep.32773. Full text in Research Archive Show summary

  Background and Aims Several characteristic features of the fecal microbiota have been described in primary sclerosing cholangitis (PSC), whereas data on mucosal microbiota are less consistent. We aimed to use a large colonoscopy cohort to investigate key knowledge gaps, including the role of gut microbiota in PSC with inflammatory bowel disease (IBD), the effect of liver transplantation (LT), and whether recurrent PSC (rPSC) may be used to define consistent microbiota features in PSC irrespective of LT. Approach and Results We included 84 PSC and 51 liver transplanted PSC patients (PSC-LT) and 40 healthy controls (HCs) and performed sequencing of the 16S ribosomal RNA gene (V3–V4) from ileocolonic biopsies. Intraindividual microbial diversity was reduced in both PSC and PSC-LT versus HCs. An expansion of Proteobacteria was more pronounced in PSC-LT (up to 19% relative abundance) than in PSC (up to 11%) and HCs (up to 8%; QFDR < 0.05). When investigating PSC before (PSC vs. HC) and after LT (rPSC vs. no-rPSC), increased variability (dispersion) in the PSC group was found. Five genera were associated with PSC before and after LT. A dysbiosis index calculated from the five genera, and the presence of the potential pathobiont, Klebsiella, were associated with reduced LT-free survival. Concomitant IBD was associated with reduced Akkermansia. Conclusions Consistent mucosal microbiota features associated with PSC, PSC-IBD, and disease severity, irrespective of LT status, highlight the usefulness of investigating PSC and rPSC in parallel, and suggest that the impact of gut microbiota on posttransplant liver health should be investigated further.

• Syversen, Silje Watterdal; Jyssum, Ingrid; Tveter, Anne Therese; Sexton, Joseph; Christensen, Ingrid Egeland & Tran, Trung [Show all 20 contributors for this article] (2022). Immunogenicity and safety of a three-dose SARS-CoV-2 vaccination strategy in patients with immune-mediated inflammatory diseases on immunosuppressive therapy. RMD Open. 8(2). doi: 10.1136/rmdopen-2022-002417. Full text in Research Archive Show summary

  Objectives Humoral vaccine responses to SARS-CoV-2 vaccines are impaired and short lasting in patients with immune-mediated inflammatory diseases (IMID) following two vaccine doses. To protect these vulnerable patients against severe COVID-19 disease, a three-dose primary vaccination strategy has been implemented in many countries. The aim of this study was to evaluate humoral response and safety of primary vaccination with three doses in patients with IMID. Methods Patients with IMID on immunosuppressive therapy and healthy controls receiving three-dose and two-dose primary SARS-CoV-2 vaccination, respectively, were included in this prospective observational cohort study. Anti-Spike antibodies were assessed 2–4 weeks, and 12 weeks following each dose. The main outcome was anti-Spike antibody levels 2–4 weeks following three doses in patients with IMID and two doses in controls. Additional outcomes were the antibody decline rate and adverse events. Results 1100 patients and 303 controls were included. Following three-dose vaccination, patients achieved median (IQR) antibody levels of 5720 BAU/mL (2138–8732) compared with 4495 (1591–6639) in controls receiving two doses, p=0.27. Anti-Spike antibody levels increased with median 1932 BAU/mL (IQR 150–4978) after the third dose. The interval between the vaccine doses and vaccination with mRNA-1273 or a combination of vaccines were associated with antibody levels following the third dose. Antibody levels had a slower decline-rate following the third than the second vaccine dose, p<0.001. Adverse events were reported by 464 (47%) patients and by 196 (78%) controls. Disease flares were reported by 70 (7%) patients. Conclusions This study shows that additional vaccine doses to patients with IMID contribute to strong and sustained immune-responses comparable to healthy persons vaccinated twice, and supports repeated vaccination of patients with IMID. Trial registration number NCT04798625.

• Hammersbøen, Kristin Reine; Jahnsen, Jørgen; Brynskov, Jørn; Molander, Pauliina; Eberhardson, Michael & Davidsdottir, Loà G. [Show all 13 contributors for this article] (2022). Therapeutic drug monitoring in inflammatory bowel disease: implementation, utilization, and barriers in clinical practice in Scandinavia. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. doi: 10.1080/00365521.2022.2108684. Full text in Research Archive Show summary

  Background and aims Therapeutic drug monitoring (TDM) may optimize biologic and thiopurine therapies in inflammatory bowel disease (IBD). The study aimed to investigate implementation and utilization of TDM in Scandinavia. Methods A web-based questionnaire on the use of TDM was distributed to Scandinavian gastroenterologists via the national societies. Results In total, 297 IBD physicians prescribing biologic therapies, equally distributed between community and university hospitals, were included (response rate 42%) (Norway 118 (40%), Denmark 86 (29%), Sweden 50 (17%), Finland 33 (11%), Iceland 10 (3%)). Overall, TDM was applied during biologic therapies by 87%, and for TNF-inhibitors >90%. Among the users, reactive and proactive TDM were utilized by 90% and 63%, respectively. Danish physicians were significantly less inclined to use TDM compared to other Scandinavian countries; (58% vs 98%); OR 0.03 [0.01–0.09], p < 0.001). Reactive TDM was commonly applied at primary (74%) and secondary (99%) treatment failure. Proactive TDM was used by 80% during maintenance therapy and 56% during induction and more commonly utilized in Norway (p < 0.001), and by physicians managing >10 IBD patients/week (p = 0.005). TDM scenarios were interpreted in accord with available evidence but with discrepancies for proactive TDM. The main barriers to TDM were lack of guidelines (51%) and time lag between sampling and results (49%). TDM of thiopurines was routinely used by 87%. Conclusion TDM of biologic and thiopurine therapies has been broadly implemented into clinical practice in Scandinavia. However, physicians call for TDM guidelines detailing indications and interpretations of test results along with improved test response times.

• Nguyen, Nghia H.; Solitano, Virginia; Vuyyuru, Sudheer K.; MacDonald, John K.; Syversen, Silje Watterdal & Jørgensen, Kristin Kaasen [Show all 10 contributors for this article] (2022). Proactive Therapeutic Drug Monitoring Versus Conventional Management for Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis. Gastroenterology. ISSN 0016-5085. 163(4), p. 937–949.e2. doi: 10.1053/j.gastro.2022.06.052. Full text in Research Archive
• Christensen, Ingrid Egeland; Jyssum, Ingrid; Tveter, Anne Therese; Sexton, Joseph; Tran, Trung & Mjaaland, Siri [Show all 19 contributors for this article] (2022). The persistence of anti-Spike antibodies following two SARS-CoV-2 vaccine doses in patients on immunosuppressive therapy compared to healthy controls—a prospective cohort study. BMC Medicine. 20(1), p. 1–13. doi: 10.1186/s12916-022-02587-8. Full text in Research Archive Show summary

  Background The durability of vaccine-induced humoral immunity against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive therapy is not known. The aim of this study was to compare the persistence of anti-Spike antibodies following two-dose SARS-CoV-2 vaccination between IMID patients and healthy controls and to identify factors associated with antibody decline. Methods IMID patients on immunosuppressive medication enrolled in the prospective observational Nor-vaC study were included. Participants received two-dose SARS-CoV-2 vaccination. Serum collected at two time points following vaccination (first assessment within 6–48 days, second within 49–123 days) were analyzed for antibodies binding the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein. Multivariable regression models estimated percent reduction in anti-RBD over 30 days and factors associated with reduction. Results A total of 1108 patients (403 rheumatoid arthritis, 195 psoriatic arthritis, 195 spondyloarthritis, 124 ulcerative colitis, 191 Crohn’s disease) and 134 controls provided blood samples within the defined intervals (median 19 days [IQR 15–24] and 97 days [87–105] after second vaccine dose). Antibody levels were lower in patients compared to controls at both time points, with median anti-RBD 2806 BAU/ml [IQR 1018–6068] in patients and 6187 BAU/ml [4105–7496] in controls (p<0.001) at first assessment, and 608 BAU/ml [IQR 58–1053] in patients and 1520 BAU/ml [979–3766] in controls (p<0.001) at second assessment. At second assessment, low anti-RBD antibody levels (defined as <200 BAU/ml) were found in 449 (41%) patients, and 6 (5%) controls (p<0.001). The change was − 83% in patients and − 66% in controls (p<0.001). Patients had a greater estimated 30 days percent reduction in anti-RBD levels compared to controls − 4.9 (95% CI − 7.4 to − 2.4), (p<0.05). Among therapies, mono- or combination treatment with tumor necrosis factor inhibitors was associated with the greatest decline. Conclusions Within 4 months after vaccination, antibody levels declined considerably in both IMID patients and controls. Patients had lower initial antibody levels and a more pronounced decline compared to healthy controls and were therefore more likely to decline to low antibody levels. These results support that IMID patients need additional vaccine doses at an earlier stage than healthy individuals.

• Jyssum, Ingrid; Kared, Hassen; Tran, Trung; Tveter, Anne Therese; Provan, Sella Aarrestad & Sexton, Joseph [Show all 22 contributors for this article] (2021). Humoral and cellular immune responses to two and three doses of SARS-CoV-2 vaccines in rituximab-treated patients with rheumatoid arthritis: a prospective, cohort study. The Lancet Rheumatology. 00. doi: 10.1016/S2665-9913(21)00394-5. Full text in Research Archive Show summary

  Background In rituximab-treated patients with rheumatoid arthritis, humoral and cellular immune responses after two or three doses of SARS-CoV-2 vaccines are not well characterised. We aimed to address this knowledge gap. Methods This prospective, cohort study (Nor-vaC) was done at two hospitals in Norway. For this sub-study, we enrolled patients with rheumatoid arthritis on rituximab treatment and healthy controls who received SARS-CoV-2 vaccines according to the Norwegian national vaccination programme. Patients with insufficient serological responses to two doses (antibody to the receptor-binding domain [RBD] of the SARS-CoV-2 spike protein concentration <100 arbitrary units [AU]/mL) were allotted a third vaccine dose. Antibodies to the RBD of the SARS-CoV-2 spike protein were measured in serum 2–4 weeks after the second and third doses. Vaccine-elicited T-cell responses were assessed in vitro using blood samples taken before and 7–10 days after the second dose and 3 weeks after the third dose from a subset of patients by stimulating cryopreserved peripheral blood mononuclear cells with spike protein peptides. The main outcomes were the proportions of participants with serological responses (anti-RBD antibody concentrations of ≥70 AU/mL) and T-cell responses to spike peptides following two and three doses of SARS-CoV-2 vaccines. The study is registered at ClinicalTrials.gov, NCT04798625, and is ongoing. Findings Between Feb 9, 2021, and May 27, 2021, 90 patients were enrolled, 87 of whom donated serum and were included in our analyses (69 [79·3%] women and 18 [20·7%] men). 1114 healthy controls were included (854 [76·7%] women and 260 [23·3%] men). 49 patients were allotted a third vaccine dose. 19 (21·8%) of 87 patients, compared with 1096 (98·4%) of 1114 healthy controls, had a serological response after two doses (p<0·0001). Time since last rituximab infusion (median 267 days [IQR 222–324] in responders vs 107 days [80–152] in non-responders) and vaccine type (mRNA-1273 vs BNT162b2) were significantly associated with serological response (adjusting for age and sex). After two doses, 10 (53%) of 19 patients had CD4+ T-cell responses and 14 (74%) had CD8+ T-cell responses. A third vaccine dose induced serological responses in eight (16·3%) of 49 patients, but induced CD4+ and CD8+ T-cell responses in all patients assessed (n=12), including responses to the SARS-CoV-2 delta variant (B.1.617.2). Adverse events were reported in 32 (48%) of 67 patients and in 191 (78%) of 244 healthy controls after two doses, with the frequency not increasing after the third dose. There were no serious adverse events or deaths. Interpretation This study provides important insight into the divergent humoral and cellular responses to two and three doses of SARS-CoV-2 vaccines in rituximab-treated patients with rheumatoid arthritis. A third vaccine dose given 6–9 months after a rituximab infusion might not induce a serological response, but could be considered to boost the cellular immune response.

• Syversen, Silje Watterdal; Jørgensen, Kristin Kaasen; Goll, Guro Løvik; Brun, Marthe Kirkesæther; Sandanger, Øystein & Hammersbøen, Kristin Reine [Show all 33 contributors for this article] (2021). Effect of Therapeutic Drug Monitoring vs Standard Therapy During Maintenance Infliximab Therapy on Disease Control in Patients With Immune-Mediated Inflammatory Diseases: A Randomized Clinical Trial. Journal of the American Medical Association (JAMA). ISSN 0098-7484. 326(23), p. 2375–2384. doi: 10.1001/jama.2021.21316. Full text in Research Archive Show summary

  IMPORTANCE Proactive therapeutic drug monitoring (TDM), consisting of individualized treatment based on scheduled assessments of serum drug levels, has been proposed as an alternative to standard therapy to optimize efficacy and safety of infliximab and other biologic drugs. However, it remains unclear whether proactive TDM improves clinical outcomes during maintenance therapy. OBJECTIVE To assess whether proactive TDM during maintenance therapy with infliximab improves treatment efficacy by preventing disease worsening compared with standard infliximab therapy without TDM. DESIGN, SETTING, AND PARTICIPANTS Randomized, parallel-group, open-label clinical trial including 458 adults with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn disease, or psoriasis undergoing maintenance therapy with infliximab in 20 Norwegian hospitals. Patients were recruited from June 7, 2017, to December 12, 2019. Final follow-up took place on December 14, 2020. INTERVENTIONS Patients were randomized 1:1 to proactive TDM with dose and interval adjustments based on scheduled monitoring of serum drug levels and antidrug antibodies (TDM group; n = 228) or to standard infliximab therapy without drug and antibody level monitoring (standard therapy group; n = 230). MAIN OUTCOME AND MEASURES The primary outcomewas sustained disease control without disease worsening, defined by disease-specific composite scores or consensus about disease worsening between patient and physician leading to a major change in treatment (switching to another biologic drug, adding an immunosuppressive drug including glucocorticoids, or increasing the infliximab dose), during the 52-week study period. RESULTS Among 458 randomized patients (mean age, 44.8 [SD, 14.3] years; 216 women [49.8%]), 454 received their randomly allocated intervention and were included in the full analysis set. The primary outcome of sustained disease control without disease worsening was observed in 167 patients (73.6%) in the TDM group and 127 patients (55.9%) in the standard therapy group. The estimated adjusted difference was 17.6%(95%CI, 9.0%-26.2%; P < .001) favoring TDM. Adverse events were reported in 137 patients (60%) and 142 patients (63%) in the TDM and standard therapy groups, respectively. CONCLUSIONS AND RELEVANCE Among patients with immune-mediated inflammatory diseases undergoing maintenance therapy with infliximab, proactive TDMwas more effective than treatment without TDM in sustaining disease control without diseaseworsening. Further research is needed to compare proactive TDM with reactive TDM, to assess the effects on long-term disease complications, and to evaluate the cost-effectiveness of this approach. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03074656

• Syversen, Silje Watterdal; Goll, Guro Løvik; Jørgensen, Kristin Kaasen; Sandanger, Øystein; Sexton, Joseph & Olsen, Inge Christoffer [Show all 33 contributors for this article] (2021). Effect of Therapeutic Drug Monitoring vs Standard Therapy During Infliximab Induction on Disease Remission in Patients With Chronic Immune-Mediated Inflammatory Diseases: A Randomized Clinical Trial. Journal of the American Medical Association (JAMA). ISSN 0098-7484. 325(17), p. 1744–1754. doi: 10.1001/jama.2021.4172. Full text in Research Archive Show summary

  Importance: Proactive therapeutic drug monitoring (TDM), defined as individualized drug dosing based on scheduled monitoring of serum drug levels, has been proposed as an alternative to standard therapy to maximize efficacy and safety of infliximab and other biological drugs. However, whether proactive TDM improves clinical outcomes when implemented at the time of drug initiation, compared with standard therapy, remains unclear. Objective: To assess whether TDM during initiation of infliximab therapy improves treatment efficacy compared with standard infliximab therapy without TDM. Design, setting, and participants: Randomized, parallel-group, open-label clinical trial of 411 adults with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn disease, or psoriasis initiating infliximab therapy in 21 hospitals in Norway. Patients were recruited from March 1, 2017, to January 10, 2019. Final follow-up occurred on November 5, 2019. Interventions: Patients were randomized 1:1 to receive proactive TDM with dose and interval adjustments based on scheduled monitoring of serum drug levels and antidrug antibodies (TDM group; n = 207) or standard infliximab therapy without drug and antibody level monitoring (standard therapy group; n = 204). Main outcomes and measures: The primary end point was clinical remission at week 30. Results: Among 411 randomized patients (mean age, 44.7 [SD, 14.9] years; 209 women [51%]), 398 (198 in the TDM group and 200 in the standard therapy group) received their randomized intervention and were included in the full analysis set. Clinical remission at week 30 was achieved in 100 (50.5%) of 198 and 106 (53.0%) of 200 patients in the TDM and standard therapy groups, respectively (adjusted difference, 1.5%; 95% CI, -8.2% to 11.1%; P = .78). Adverse events were reported in 135 patients (68%) and 139 patients (70%) in the TDM and standard therapy groups, respectively. Conclusions and relevance: Among patients with immune-mediated inflammatory diseases initiating treatment with infliximab, proactive therapeutic drug monitoring, compared with standard therapy, did not significantly improve clinical remission rates over 30 weeks. These findings do not support routine use of therapeutic drug monitoring during infliximab induction for improving disease remission rates.

• Vesterhus, Mette Nåmdal; Wiencke, Kristine; Haukeland, John Willy; Frigstad, Svein Oskar; Karlsen, Lars Normann & Jørgensen, Kristin Kaasen [Show all 7 contributors for this article] (2021). Klinisk oversiktsartikkel: Diagnostikk og behandling av autoimmun hepatitt. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 141. doi: 10.4045/tidsskr.20.1045. Full text in Research Archive
• Haukeland, John Willy; Småstuen, Milada Cvancarova; Pålsdatter, Pia Pernille; Ismail, Moonisah; Zbigniew, Konopski & Jørgensen, Kristin Kaasen [Show all 8 contributors for this article] (2020). Effect of gender on mortality and causes of death in cirrhotic patients with gastroesophageal varices. A retrospective study in Norway. PLOS ONE. 15(3), p. 1–16. doi: 10.1371/journal.pone.0230263. Full text in Research Archive Show summary

  Background & aims The prognostic role of gender in patients with liver cirrhosis is not fully understood. Our primary aim was to assess how gender affects cumulative incidence and risk of death without liver transplantation (LT) in cirrhotic patients with gastroesophageal varices. Secondary aims were to assess the relationship between gender and cause specific death, risk of variceal bleeding and incidence rates of gastroesophageal varices in patients with cirrhosis. Methods All new patients with gastroesophageal varices due to liver cirrhosis at Oslo University Hospital between 2006 and May 2016 were identified. Clinical data were retrieved retrospectively from hospital files. Causes of death were classified according to a specified protocol in cases of in-hospital-death, otherwise by data from the Norwegian Death Registry. Competing risk analyses were used to calculate cumulative incidences and risks of i) all-cause death, ii) cause-specific death and iii) variceal bleeding or re-bleeding. Results Cumulative one- and five years incidence of death without LT in 266 included patients were 28% and 51%, respectively. In univariate analysis, risk of death was positively associated with age, Child Pugh class, alcoholic liver disease and presentation with variceal bleeding, and negatively associated with female sex. In a multivariate model, risk of death without LT was associated with female sex (SHR 0.59 [0.40–0.86]), age (SHR 1.05 [1.04–1.07] per year), Child Pugh class B (SHR 1.54 [1.03–2.32]) and Child Pugh class C (SHR 4.29 [2.57–7.17]). Variceal bleeding caused 27% of deaths. Adjusting for age and Child Pugh score, a trend towards reduced risk of death due to variceal bleeding was seen in women (SHR 0.53; [0.26–1.06]). High alcohol consumption was associated with increased risk of first variceal bleeding, both at univariate analysis (SHR 7.73 [1.71–34.9]) and multivariate analysis (SHR 13.9 [2.51–77.0]). Conclusions Reduced mortality due to variceal bleeding may contribute to improved survival without LT in cirrhotic women with gastroesophageal varices.

• Syversen, Silje Watterdal; Goll, Guro Løvik; Jørgensen, Kristin Kaasen; Olsen, Inge Christoffer; Sandanger, Øystein & Gehin, Johanna Elin [Show all 13 contributors for this article] (2020). Therapeutic drug monitoring of infliximab compared to standard clinical treatment with infliximab: study protocol for a randomised, controlled, open, parallel-group, phase IV study (The NOR-DRUM study). Trials. 21(13). doi: 10.1186/s13063-019-3734-4. Full text in Research Archive Show summary

  Background Infliximab (INX) and other tumour necrosis factor inhibitors (TNFi) have revolutionised the treatment of several immune mediated inflammatory diseases. Still, many patients do not respond sufficiently to therapy or lose efficacy over time. The large interindividual variation in serum drug concentrations on standard doses and the development of anti-drug antibodies are thought to be major reasons for treatment failures. Therapeutic drug monitoring (TDM), an individualised treatment strategy based on systematic assessments of serum drug concentrations, has been proposed as a clinical tool to optimise efficacy of INX treatment. TDM seems reasonable both from a clinical and an economical point of view, but the effectiveness of this treatment strategy has not yet been demonstrated in randomised clinical trials. The NORwegian DRUg Monitoring study (NOR-DRUM) aims to assess the effectiveness of TDM, both with regard to the achievement of remission in patients starting INX treatment (part A) as well as to maintain disease control in patients on INX treatment (part B). Methods The NOR-DRUM study is a randomised, open, controlled, parallel-group, comparative, multi-centre, national, superiority, phase IV study with two separate parts, NOR-DRUM A and NOR-DRUM B. Patients with rheumatoid arthritis, psoriatic arthritis, spondyloarthritis, ulcerative colitis, Crohn’s disease and psoriasis are included. In both study parts participants are randomised 1:1 to either TDM of infliximab (intervention group) or to standard treatment with infliximab without knowledge of drug levels or ADAb status (control group). NOR-DRUM A will include 400 patients starting INX therapy. The primary outcome is remission at 30 weeks. In NOR-DRUM B, 450 patients on maintenance treatment with INX will be included. The primary endpoint is occurrence of disease worsening during the 52-week study period. Discussion As the first trial to assess the effectiveness, safety and cost-effectiveness of TDM in patients receiving TNFi for a range of immune mediated inflammatory diseases, we hope that the NOR-DRUM study will contribute to the advancement of evidence based personalised treatment with biological medicines. Trial registration Clinicaltrials.gov, NCT03074656. Registered on 090317.

• Hedin, Charlotte Rose Hawkey; Sado, Gina; Ndegwa, Nelson; Lytvyak, Ellina; Mason, Andrew & Montano-Loza, Aldo [Show all 36 contributors for this article] (2020). Effects of Tumor Necrosis Factor Antagonists in Patients With Primary Sclerosing Cholangitis. Clinical Gastroenterology and Hepatology. ISSN 1542-3565. 18(10), p. 2295–2304.e2. doi: 10.1016/j.cgh.2020.02.014. Full text in Research Archive
• Jørgensen, Kristin Kaasen; Goll, Guro Løvik; Sexton, Joseph; Bolstad, Nils; Olsen, Inge Christoffer & Asak, Øivind Wessel [Show all 29 contributors for this article] (2020). Efficacy and safety of CT-P13 in inflammatory bowel disease after switching from originator infliximab: Exploratory analyses from the NOR-SWITCH main and extension trials. BioDrugs. ISSN 1173-8804. 34(5), p. 681–694. doi: 10.1007/s40259-020-00438-7. Full text in Research Archive Show summary

  Background: The NOR-SWITCH main and extension trials demonstrated that switching from originator to biosimilar infliximab (CT-P13) is efficacious and safe across six diseases. However, a subgroup analysis of Crohn's disease (CD) in the main trial displayed a close to significant difference favouring originator infliximab, and more scientific data have therefore been requested. Objective: The aim was to assess treatment efficacy, safety, and immunogenicity in an explorative subgroup analysis in CD and ulcerative colitis (UC) in the NOR-SWITCH trials. Patients and methods: The 52-week, randomised, non-inferiority, double-blind, multicentre, phase 4 NOR-SWITCH study was followed by a 26-week open extension trial where all patients received treatment with CT-P13. Treatment efficacy, safety, and immunogenicity in CD and UC were assessed throughout the 78-week study period. Results: The main and extension trials included 155 and 93 patients with CD and 93 and 80 patients with UC, respectively. Demographic and baseline characteristics were comparable in both treatment arms within patient groups. There were no differences in the main and extension trials regarding changes in activity indices, C-reactive protein, faecal calprotectin, patient's and physician's global assessment of disease activity and patient-reported outcome measures in CD and UC. Moreover, comparable results were also demonstrated for trough serum levels, presence of anti-drug antibodies, and reported adverse events. Conclusion: Efficacy, safety, and immunogenicity of both the originator and biosimilar infliximab were comparable in CD and UC in the NOR-SWITCH main and extension trials. These explorative subgroup analyses confirm that there are no significant concerns related to switching from originator infliximab to CT-P13 in CD and UC.

• Goll, Guro Løvik; Jørgensen, Kristin Kaasen; Sexton, Joseph; Olsen, Inge Christoffer; Bolstad, Nils & Haavardsholm, Espen A. [Show all 48 contributors for this article] (2019). Long‐term efficacy and safety of biosimilar infliximab (CT‐P13) after switching from originator infliximab: Open‐label extension of the NOR‐SWITCH trial. Journal of Internal Medicine. ISSN 0954-6820. 285(6), p. 653–669. doi: 10.1111/joim.12880. Full text in Research Archive Show summary

  Background and objectives The 52‐week, randomized, double‐blind, noninferiority, government‐funded NOR‐SWITCH trial demonstrated that switching from infliximab originator to less expensive biosimilar CT‐P13 was not inferior to continued treatment with infliximab originator. The NOR‐SWITCH extension trial aimed to assess efficacy, safety and immunogenicity in patients on CT‐P13 throughout the 78‐week study period (maintenance group) versus patients switched to CT‐P13 at week 52 (switch group). The primary outcome was disease worsening during follow‐up based on disease‐specific composite measures. Methods Patients were recruited from 24 Norwegian hospitals, 380 of 438 patients who completed the main study: 197 in the maintenance group and 183 in the switch group. In the full analysis set, 127 (33%) had Crohn's disease, 80 (21%) ulcerative colitis, 67 (18%) spondyloarthritis, 55 (15%) rheumatoid arthritis, 20 (5%) psoriatic arthritis and 31 (8%) chronic plaque psoriasis. Results Baseline characteristics were similar in the two groups at the time of switching (week 52). Disease worsening occurred in 32 (16.8%) patients in the maintenance group vs. 20 (11.6%) in the switch group (per‐protocol set). Adjusted risk difference was 5.9% (95% CI −1.1 to 12.9). Frequency of adverse events, anti‐drug antibodies, changes in generic disease variables and disease‐specific composite measures were comparable between arms. The study was inadequately powered to detect noninferiority within individual diseases. Conclusion The NOR‐SWITCH extension showed no difference in safety and efficacy between patients who maintained CT‐P13 and patients who switched from originator infliximab to CT‐P13, supporting that switching from originator infliximab to CT‐P13 is safe and efficacious.

• Lindström, Lina; Jørgensen, Kristin Kaasen; Boberg, Kirsten Muri; Castedal, Maria; Rasmussen, Allan & Rostved, Andreas Arendtsen [Show all 9 contributors for this article] (2018). Risk factors and prognosis for recurrent primary sclerosing cholangitis after liver transplantation: a Nordic Multicentre Study. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 53(3), p. 297–304. doi: 10.1080/00365521.2017.1421705. Full text in Research Archive
• Chung, Brian Kai-Ho; Henriksen, Eva Kristine Klemsdal; Jørgensen, Kristin Kaasen; Karlsen, Tom Hemming; Hirschfield, Gideon & Liaskou, Evaggelia (2018). Gut and Liver B Cells of Common Clonal Origin in Primary Sclerosing Cholangitis-Inflammatory Bowel Disease. Hepatology communications.. 2(8), p. 960–971. doi: 10.1002/hep4.1200. Full text in Research Archive Show summary

  B cells express an antigen‐specific B‐cell receptor (BCR) and may contribute to liver inflammation by recognizing shared antigens in the gut and liver. Herein, we used high‐throughput BCR sequencing of the immunoglobulin heavy chain, specifically the complementarity‐determining region 3 (CDR3), to characterize the B‐cell repertoire of freshly‐frozen paired gut and liver tissue samples from patients with primary sclerosing cholangitis (PSC) and concurrent inflammatory bowel disease (IBD) (PSC‐IBD, n = 10) and paired formalin‐fixed paraffin‐embedded (FFPE) tumor‐adjacent normal colon and liver tissue from patients with colorectal liver metastases (controls, n = 10). We observed significantly greater numbers of B cells (P < 0.01) and unique B‐cell clonotypes (P < 0.05) in gut samples compared to liver samples of patients with PSC‐IBD, whereas BCR sequences in FFPE normal gut and liver samples were nearly absent (14 ± 5 clonotypes; mean ± SD; n = 20). In PSC‐IBD, an average of 8.3% (range, 1.6%‐18.0%) of B‐cell clonotypes were found to overlap paired gut and liver samples following the exclusion of memory clonotypes reported in the blood of healthy controls. Overlapping gut and liver clonotypes showed stronger evidence of antigen‐driven activation compared to non‐overlapping clonotypes, including shorter CDR3 lengths and higher counts of somatic hypermutation (P < 0.0001). Conclusion: A proportion of gut and liver B cells originate from a common clonal origin (i.e., likely to recognize the same antigen) in patients with PSC which suggests B‐cell antigens are shared across the gut–liver axis. (Hepatology Communications 2018; 00:000‐000)

• Jahnsen, Jørgen & Jørgensen, Kristin Kaasen (2017). Experience with Biosimilar Infliximab (Remsima?) in Norway. Digestive Diseases. ISSN 0257-2753. 35(1-2), p. 83–90. doi: 10.1159/000449088. Full text in Research Archive
• Henriksen, Eva Kristine Klemsdal; Jørgensen, Kristin Kaasen; Kaveh, Fatemeh; Holm, Kristian; Hamm, David & Olweus, Johanna [Show all 14 contributors for this article] (2017). Gut and liver T-cells of common clonal origin in primary sclerosing cholangitis-inflammatory bowel disease. Journal of Hepatology. ISSN 0168-8278. 66(1), p. 116–122. doi: 10.1016/j.jhep.2016.09.002. Full text in Research Archive
• Jørgensen, Kristin Kaasen; Olsen, Inge Christoffer; Goll, Guro Løvik; Lorentzen, Merete; Bolstad, Nils & Haavardsholm, Espen A. [Show all 10 contributors for this article] (2017). Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, double-blind, non-inferiority trial. The Lancet. ISSN 0140-6736. 389(10086), p. 2304–2316. doi: 10.1016/S0140-6736(17)30068-5. Full text in Research Archive Show summary

  Background TNF inhibitors have improved treatment of Crohn's disease, ulcerative colitis, spondyloarthritis, rheumatoid arthritis, psoriatic arthritis, and chronic plaque psoriasis, but are expensive therapies. The aim of NOR-SWITCH was to examine switching from originator infliximab to the less expensive biosimilar CT-P13 regarding efficacy, safety, and immunogenicity. Methods The study is a randomised, non-inferiority, double-blind, phase 4 trial with 52 weeks of follow-up. Adult patients on stable treatment with infliximab originator treated in a hospital setting for at least 6 months were eligible for participation. Patients with informed consent were randomised in a 1:1 ratio to either continued infliximab originator or to switch to CT-P13 treatment, with unchanged dosing regimen. Data were collected at infusion visits in 40 Norwegian study centres. Patients, assessors, and patient care providers were masked to treatment allocation. The primary endpoint was disease worsening during 52-week follow-up. 394 patients in the primary per-protocol set were needed to show a non-inferiority margin of 15%, assuming 30% disease worsening in each group. This trial is registered with ClinicalTrials.gov, number NCT02148640. Findings Between Oct 24, 2014, and July 8, 2015, 482 patients were enrolled and randomised (241 to infliximab originator, 241 to CT-P13 group; one patient was excluded from the full analysis and safety set for CT-P13) and 408 were included in the per-protocol set (202 in the infliximab originator group and 206 in the CT-P13 group). 155 (32%) patients in the full analysis set had Crohn's disease, 93 (19%) had ulcerative colitis, 91 (19%) had spondyloarthritis, 77 (16%) had rheumatoid arthritis, 30 (6%) had psoriatic arthritis, and 35 (7%) had chronic plaque psoriasis. Disease worsening occurred in 53 (26%) patients in the infliximab originator group and 61 (30%) patients in the CT-P13 group (per-protocol set; adjusted treatment difference −4·4%, 95% CI −12·7 to 3·9). The frequency of adverse events was similar between groups (for serious adverse events, 24 [10%] for infliximab originator vs 21 [9%] for CT-P13; for overall adverse events, 168 [70%] vs 164 [68%]; and for adverse events leading to discontinuation, nine [4%] vs eight [3%], respectively). Interpretation The NOR-SWITCH trial showed that switching from infliximab originator to CT-P13 was not inferior to continued treatment with infliximab originator according to a prespecified non-inferiority margin of 15%. The study was not powered to show non-inferiority in individual diseases.

• Zenouzi, Roman; Weismüller, Tobias J; Jørgensen, Kristin Kaasen; Bubenheim, Michael; Lenzen, Henrike & Hübener, Peter [Show all 19 contributors for this article] (2016). No Evidence That Azathioprine Increases Risk of Cholangiocarcinoma in Patients With Primary Sclerosing Cholangitis. Clinical Gastroenterology and Hepatology. ISSN 1542-3565. 14(12), p. 1806–1812. doi: 10.1016/j.cgh.2016.07.032. Full text in Research Archive
• Kevans, David; Tyler, Andrea D.; Holm, Kristian; Jørgensen, Kristin Kaasen; Vatn, Morten H & Karlsen, Tom Hemming [Show all 11 contributors for this article] (2016). Characterization of Intestinal Microbiota in Ulcerative Colitis Patients with and without Primary Sclerosing Cholangitis. Journal of Crohn's and Colitis. ISSN 1873-9946. 10(3), p. 330–337. doi: 10.1093/ecco-jcc/jjv204. Full text in Research Archive
• Jørgensen, Silje Fjellgård; Reims, Henrik Mikael; Frydenlund, Didrik Søli; Holm, Kristian; Paulsen, Vemund & Michelsen, Annika [Show all 23 contributors for this article] (2016). A Cross-Sectional Study of the Prevalence of Gastrointestinal Symptoms and Pathology in Patients with Common Variable Immunodeficiency. American Journal of Gastroenterology. ISSN 0002-9270. 111(10), p. 1467–1475. doi: 10.1038/ajg.2016.329. Full text in Research Archive
• Block, M; Jørgensen, Kristin Kaasen; Øresland, Tom; Lindholm, E; Grzyb, Krzysztof & Småstuen, Milada Cvancarova [Show all 9 contributors for this article] (2014). Colectomy for patients with ulcerative colitis and primary sclerosing cholangitis - What next? Journal of Crohn's and Colitis. ISSN 1873-9946. 8(5), p. 421–430. doi: 10.1016/j.crohns.2013.10.008. Full text in Research Archive
• Jørgensen, Kristin Kaasen; Lindstrøm, Lina; Småstuen, Milada Cvancarova; Karlsen, Tom Hemming; Castedal, Maria & Friman, Styrbjörn [Show all 15 contributors for this article] (2013). Immunosuppression after liver transplantation for primary sclerosing cholangitis influences activity of inflammatory bowel disease. Clinical Gastroenterology and Hepatology. ISSN 1542-3565. 11(5), p. 517–523. doi: 10.1016/j.cgh.2012.12.027. Full text in Research Archive
• Jørgensen, Kristin Kaasen; Lindstrom, Lina; Cvancarova, Milada; Castedal, Maria; Friman, Styrbjörn & Schrumpf, Erik [Show all 14 contributors for this article] (2012). Colorectal neoplasia in patients with primary sclerosing cholangitis undergoing liver transplantation: a Nordic multicenter study. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 47(8-9), p. 1021–1029. doi: 10.3109/00365521.2012.685754. Full text in Research Archive
• Jørgensen, Kristin Kaasen; Grzyb, Krzysztof; Lundin, Knut E A; Clausen, Ole Petter Fraas; Aamodt, Geir & Schrumpf, Erik [Show all 8 contributors for this article] (2012). Inflammatory bowel disease in patients with primary sclerosing cholangitis: clinical characterization in liver transplanted and non transplanted pateints. Inflammatory Bowel Diseases. ISSN 1078-0998. 18(3), p. 536–545. doi: 10.1002/ibd.21699. Full text in Research Archive
• Ricanek, Petr; Lothe, Sheba Maria; Szpinda, Irena; Jorde, Anne Tomine; Brackmann, Stephan & Perminow, Gøri [Show all 10 contributors for this article] (2010). Paucity of mycobacteria in mucosal bowel biopsies from adults and children with early inflammatory bowel disease. Journal - Crohn's and Colitis Foundation of Canada. ISSN 1197-4982. 4(5), p. 561–566. doi: 10.1016/j.crohns.2010.05.003. Full text in Research Archive

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• König, Marton; Holmøy, Trygve; Nygaard, Gro Owren; Riise, Jon; Midtvedt, Karsten & Goll, Guro Løvik [Show all 11 contributors for this article] (2026). Vaccination of immunosuppressed patients. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. doi: 10.4045/tidsskr.25.0555. Full text in Research Archive
• 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
• Helgadottir, Holmfridur; Folseraas, Trine; Kemmerich, Gunter; Aabakken, Lars; Jørgensen, Kristin Kaasen & Vesterhus, Mette Nåmdal (2023). Primær skleroserende kolangitt. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 143(17). doi: 10.4045/tidsskr.23.0156. Full text in Research Archive
• Haukeland, John Willy; Vesterhus, Mette Nåmdal; Jørgensen, Kristin Kaasen; Frigstad, Svein Oskar & Karlsen, Tom Hemming (2023). FIB-4-testen som beslutningsverktøy. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 143(5). doi: 10.4045/tidsskr.23.0176. Full text in Research Archive
• Hole, Mikal Jacob; Jørgensen, Kristin Kaasen; Holm, Kristian; Braadland, Peder Rustøen; Meyer-Myklestad, Malin Holm & Medhus, Asle Wilhelm [Show all 13 contributors for this article] (2023). Reply: The mucosal gut signature in primary sclerosing cholangitis before and after liver transplantation. Is the dysbiosis index really predictive for the recurrence of PSC? Hepatology. ISSN 0270-9139. 77(6), p. E188–E189. doi: 10.1097/HEP.0000000000000340. Full text in Research Archive
• Vesterhus, Mette Nåmdal; Jørgensen, Kristin Kaasen; Frigstad, Svein Oskar; Haukeland, John Willy & Karlsen, Tom Hemming (2022). Vi trenger en ny strategi for leversykdom. 142(3). doi: 10.4045/tidsskr.21.0892. Full text in Research Archive
• Jørgensen, Kristin Kaasen; Bjørlykke, Kristin H.; Jyssum, Ingrid; Ørbo, Sofie Sager; Syversen, Silje Watterdal & Goll, Guro Løvik (2022). Studie: Trygt og effektivt med hyppige koronavaksiner til immunsupprimerte. [Journal]. Dagens medisin. Full text in Research Archive
• König, Marton; Wolf, Asia-Sophia Fumika Michaela; Ravussin, Anthony; Chopra, Adity; Tran, Trung & Torgauten, Hilde Marie [Show all 28 contributors for this article] (2022). Immunogenicity and efficacy of mRNA-COVID-19 vaccines in people with multiple sclerosis. Full text in Research Archive
• Jørgensen, Kristin Kaasen; Lundin, Knut Erik Aslaksen; Olsen, Inge Christoffer; Kvien, Tore Kristian & Jahnsen, Jørgen (2017). Efficacy of infliximab biosimilars in patients with Crohn's disease - Authors' reply. The Lancet. ISSN 0140-6736. 390(10111), p. 2436–2436. doi: 10.1016/S0140-6736(17)32463-7. Full text in Research Archive
• Jørgensen, Kristin Kaasen; Christoffer, Olsen Inge; Goll, Guro Løvik; Lorentzen, Merete; Bolstad, Nils & Berset, Ingrid Prytz [Show all 11 contributors for this article] (2017). Biosimilar Infliximab (CT-P13) is not Inferior to Originator Infliximab: Explorative IBD Subgroup-Analyses in Crohn's Disease and Ulcerative Colitis from the Nor-Switch Trial. Gastroenterology. ISSN 0016-5085. 152(5), p. 65–66. doi: 10.1016/S0016-5085(17)30572-3. Full text in Research Archive
• Jørgensen, Kristin Kaasen; Christoffer, Olsen Inge; Goll, Guro Løvik; Lorentzen, Merete; Bolstad, Nils & Berset, Ingrid Prytz [Show all 11 contributors for this article] (2017). Biosimilar infliximab (CT-P13) is not inferior to originator infliximab: explorative IBD subgroup-analyses in Crohn’s disease and ulcerative colitis from the NOR-SWITCH trial. Journal of Crohn's and Colitis. ISSN 1873-9946. 11, p. 62–63. doi: 10.1093/ecco-jcc/jjx002.099. Full text in Research Archive
• Jørgensen, Kristin Kaasen (2013). Inflammatory Bowel Disease in Primary Sclerosing Cholangitis: Clinical Characteristics in Liver Transplanted and Non-Transplanted Patients. Universitetet i Oslo. Full text in Research Archive

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