Concomitant use of azathioprine/6-mercaptopurine decreases the risk of anti-TNF-induced skin lesions

Abstract

Background: Anti-tumor necrosis factor (anti-TNF) agents are widely used to treat patients with moderate-to-severe inflammatory bowel disease (IBD). We aimed to identify the risk factors for adverse skin lesions in patients with IBD receiving anti-TNF agents and assess the effect of concomitant use of azathioprine/6-mercaptopurine (AZA/6 MP).

Methods: A total of 500 patients (404 with Crohn's disease, 96 with ulcerative colitis) who received anti-TNF agents between June 2002 and July 2013 were identified and retrospectively investigated. We compared 47 patients with IBD with skin lesions with 443 patients with IBD without skin lesions to identify risk factors by univariate and multivariate analysis. The Kaplan-Meier method was used to estimate the cumulative incidence of adverse skin lesions in relation to the concomitant use of AZA/6 MP.

Results: Eczematiform eruptions (n = 18, 38%) were the most common skin lesion type, followed by psoriasiform lesions (n = 13, 28%). A response to topical steroids was seen in 70% (33/47) of patients with skin lesions, and anti-TNF agents had to be discontinued in 9% (4/47). Concomitant use of AZA/6 MP decreased the risk of skin lesions in univariate (hazard ratio, 0.452; 95% CI, 0.251-0.814; P = 0.008) and multivariate (hazard ratio, 0.437; 95% CI, 0.242-0.790; P = 0.006) analysis. In addition, the cumulative incidence of adverse skin lesions was lower in patients on concomitant maintenance with AZA/6 MP (P = 0.009) than in those on anti-TNF monotherapy.

Conclusions: Concomitant use of AZA/6 MP may decrease the occurrence of adverse skin lesions in patients receiving anti-TNF therapy.