The Risk of Rheumatoid Arthritis, Psoriasis, and Hidradenitis Suppurativa in Patients With Inflammatory Bowel Disease Exposed to Anti-TNF: A Nationwide Danish Cohort Study

Background: Anti-TNF medications are effective therapies for rheumatoid arthritis (RA), psoriasis, hidradenitis suppurativa, and inflammatory bowel diseases, however, case reports have identified the occurrence of these diseases following initiation of anti-TNF therapy. We assessed the risk of RA, psoriasis, and hidradenitis suppurativa associated with anti-TNF therapies in patients with inflammatory bowel disease. Methods: A performed a nationwide Danish population-based cohort study, 2005-2018, to assess the effect of anti-TNF therapy on first occurrence of RA, psoriasis, or hidradenitis suppurativa (as a combined outcome and separately). Propensity scores were estimated based on covariates including comorbidities and co-medications, and anti-TNF exposed and unexposed patients were matched on propensity scores. We also compared the risk of RA, psoriasis, and hidradenitis suppurativa associated with anti-TNF monotherapy vs. azathioprine monotherapy. Findings: Our cohort included 9,036 anti-TNF exposed patients and 9,036 unexposed patients. The median age of anti-TNF exposed patients was 36 years (Q1-Q3: 26-48), 53% were female, and 50% had Crohn’s disease, while for unexposed patients the corresponding figures were 38 years (Q1-Q3: 28-51), 53%, and 48%. Anti-TNF therapy was associated with a significantly increased risk of the combined outcome (HR 1∙37, 95% CI 1∙12-1∙68), and with numerically increased HRs for RA (HR, 1∙60; 95% CI 0∙78-3∙31), psoriasis (HR, 1∙32; 95% CI 1∙05-1∙66), and hidradenitis suppurativa (HR, 1∙64; 95% CI 0∙86-3∙12). When compared to azathioprine monotherapy, anti-TNF monotherapy was also associated with a significantly increased risk of the combined outcome (HR 2∙42, 95% CI 1∙27-4∙62), with a 5-fold increased risk of RA (HR 5∙10, 95% CI 1∙03-25∙28). Interpretation: In this nationwide population-based cohort, anti-TNF therapy was, paradoxically, associated with an increased risk of RA, psoriasis, and hidradenitis suppurativa. These data are unexpected and warrant further investigation. Funding Information: This study was financially supported by the Danish National Research Foundation, grant no. DNRF148. Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: Ethics approval is not required for register based epidemiological research in Denmark.