Objectives To evaluate the risk of gastrointestinal perforation (GIP) in subjects with RA treated with anti-TNF therapy compared to non-biological disease-modifying antirheumatic drugs (nbDMARDs).
Methods The analysis was conducted in the British Society for Rheumatology Biologics Register (BSRBR), a prospective cohort study. Patients with RA starting treatment with the TNF inhibitors etanercept (ETA), infliximab (INF) or adalimumab (ADA) and a biologic-naïve comparison cohort exposed to nbDMARDs were recruited between 2001-2009. Subjects were followed until 31/3/2011 or death, whichever came first. Events were ascribed to anti-TNF if they occurred while the patient was receiving anti-TNF therapy or within 90 days of the first missed dose. Events were attributed to the most recent drug received in patients who switched anti-TNF therapy. Cox proportional hazards model were developed to compare the rates of GIP between cohorts. A propensity score was used to balance covariates between treatment groups and included age, gender, weight, comorbidity, smoking, indexes of disease severity, use of steroids, NSAIDs, and gastroprotective drugs. Stratification by deciles of propensity score for treatment was used to adjust for confounding between the groups. Current steroid use was entered into the model as a time-varying covariate.
Results There were 58 (upper: 25, lower: 33) GI perforations: 5 in the nbDMARD cohort, 37 in the anti-TNF cohort (on drug + 90 days), and 16 in the anti-TNF cohort (off drug). In univariate analyses higher HAQ, history of hypertension, and smoking were associated with the risk of lower GIP, and use of nonselective NSAIDs at baseline and low weight with the risk of upper GIP, irrespective of anti-TNF exposure. After adjustment, treatment with TNF antagonists was associated with hazard ratio (HR) of 1.6 (95% CI 0.4 to 6.0) for all perforations, 2.7 (95% CI 0.4 to 18.1) for lower and 0.9 (95% CI 0.1 to 5.8) for upper GI perforations. Current use of steroids was the single most important predictor of GIP with adjusted HR of 2.9 (95% CI 1.5 to 5.4), but this increase of risk was confined to lower GIPs (HR 8.0, 95% CI 2.6 to 24.1).
Conclusions Anti-TNF therapy was not associated with statistically significant increase of all GI perforations, although there was a signal of possible increased risk of lower GI perforations. Current use of steroids was the single most important risk factor for lower GI perforations.
Disclosure of Interest None Declared