Abstract
Background
Tumour necrosis factor (TNF) has a central role in the pathophysiology of immune-mediated inflammatory diseases (IMIDs) including rheumatoid arthritis, psoriasis, hidradenitis suppurativa, and inflammatory bowel diseases (IBD). However, there have been case reports of patients receiving an anti-TNF therapy for one IMID subsequently developing a second IMID. We conducted a nationwide cohort study investigating the risk of incident IMID following anti-TNF exposure in patients with IBD in Denmark.
Methods
We followed patients with IBD from 1 January 2005 or date of IBD diagnosis (whichever occurred last) to an outcome event including incident diagnosis of hidradenitis suppurativa, arthropathic psoriasis, other forms of psoriasis, or rheumatoid arthritis; or emigration, death or 31 December 2018 (whichever occurred first). Patients were defined as exposed after a 3-month lag period from first anti-TNF infusion throughout follow-up, analogous to an intention-to-treat design. The lag period was censored from analyses to avoid including incipient IMIDs, unlikely to be caused by newly initiated anti-TNF treatment. We excluded patients initiating anti-TNF or with an outcome diagnosis before either 1 January 2005 or IBD diagnosis. We used Cox regression models with age as the underlying timescale, and sex, type of IBD (Crohn’s disease or ulcerative colitis), and calendar period of IBD diagnosis (in 5 year groups) as strata to estimate hazard ratios for each outcome, comparing anti-TNF users and non-users.
Results
Incidence rates (and 95% confidence intervals [CI]) as events per 100 000 person-years among anti-TNF users and non-users were, respectively, 138 (109–173) and 25.6 (22.0–29.7) for hidradenitis suppurativa, 26.3 (15.6–44.4) and 7.81 (5.95–10.2) for arthropathic psoriasis, 1177 (1085–1277) and 204 (121–189) for other forms of psoriasis, and 152 (121–189) and 95.6 (88.5–103) for rheumatoid arthritis. Hazard ratios (and 95% C.I.) were increased for hidradenitis suppurativa 2.91 (2.15–3.94), arthropathic psoriasis 2.62 (1.40–4.93), other forms of psoriasis 4.76 (4.27–5.31), and rheumatoid arthritis 2.35 (1.83–3.01).
Conclusion
The results indicate that patients with IBD receiving anti-TNF have an increased risk of IMIDs. An almost 5-fold increase in the risk of psoriasis is consistent with previous reports of psoriasiform skin lesions related to anti-TNF use. However, as more severe IBD is likely to be associated with both initiating anti-TNF and the incidence of other inflammatory diseases, the results are subject to confounding by indication. Thus, these results should be considered preliminary, and we plan to further address confounding by using propensity score methods.
Updated consensus statement on biological agents for the treatment of rheumatoid arthritis and other immune mediated inflammatory diseases (May 2003)