Background/Purpose: An increased risk of side effects, especially infections, has been reported among patients receiving tumor necrosis factor (TNF)-α blockers. Some leukocytoclastic cutaneous vasculitides reportedly occurred under TNF-α blockers used to treat various inflammatory diseases, but the risk of vasculitis with TNF-α blockers remains uncertain, especially in comparison with other immunosuppressive agents.We aimed to assess the risk of vasculitis associated with thiopurines and TNF-α blockers prescribed to manage inflammatory bowel diseases (IBD).

Methods: This nationwide population-based study included patients (≥18 years old) affiliated with the French National Health Insurance (FNHI), with an IBD diagnosis based on long-term diseases listed and/or hospital-discharge diagnoses in the FNHI database from January 2010 through 2011, and followed until 31 December 2014. The risks of vasculitis associated with exposure to thiopurines or TNF-α blockers were compared using a Cox regression model adjusted for baseline sociodemographic characteristics and comorbidities. The primary outcome was incident vasculitis.

Results: Among the 193,663 IBD patients included in our analysis, 173 developed vasculitis, mainly IgA vasculitis (n=41), hypersensitivity vasculitis (n=41) and large-vessel vasculitis (n=39). Incidences per 100,000 person-years were 4.9 for IgA vasculitis, 4.9 for hypersensitivity vasculitis, 4.6 for large vessel vasculitis, 2.1 for ANCA-associated vasculitis and 1.2 for medium-sized–vessel vasculitis.

Compared with patients not exposed to TNF-α blockers or thiopurines during the study period, TNF-α blockers (hazard ratio [HR], 2.39; 95% confidence interval [95% CI], 1.49–3.84) were associated with a higher risk of vasculitis but not thiopurines (HR, 0.72; 95% CI, 0.40–1.31).The magnitude of TNF-α-blocker–associated risk was higher for patients with ulcerative colitis (HR, 4.07; 95% CI, 1.96–8.47) than those with Crohn’s disease (HR, 1.75; 95% CI, 0.95–3.22). The risk of vasculitis with TNF-α–blocker exposure was independently associated with older age (per 1-year increment, HR, 1.09; 95% CI, 1.04–1.15), female sex (HR, 1.47; 95% CI, 1.08–2.00), cardiovascular disease (HR, 2.01; 95% CI, 1.33–3.04) and diabetes mellitus (HR, 1.77; 95% CI, 1.12–2.79).

Finally, exploratory analyses showed that exposure to TNF-α blockers was not associated with a specific subtype of vasculitis: IgA vasculitis (HR, 3.11; 95% CI, 1.36–7.09), hypersensitivity vasculitis (HR, 3.48; 95% CI, 1.52–1.7.95), large-vessel vasculitis (HR, 2.56; 95% CI, 0.87–7.57) or ANCA-associated vasculitides (HR, 7.68; 95% CI, 1.99–29.7).

Conclusion: Based on a nationwide cohort study of IBD patients in France, TNF-α blockers were associated with an increased risk of vasculitis, unlike thiopurines. Cardiovascular disease and diabetes mellitus were also associated with the risk of vasculitis, suggesting relationships among atherosclerosis, chronic hyperglycemic state andinflammation.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/risk-of-vasculitis-associated-with-inflammatory-bowel-diseases-evidence-for-a-role-of-tnf-%ce%b1-blockers/