Bisphosphonate Increases Risk of Peptic Ulcer in Rheumatoid Arthritis Patients On Long-Term Non-Steroidal Anti-Inflammatory Drug Therapy

Abstract

Objective: Rheumatoid arthritis (RA) patients are at increased risk of developing peptic ulcer induced by non-steroidal anti-inflammatory drugs (NSAIDs). However, despite the recent introduction of a variety of new drugs for the treatment of RA patients, the impact of potential drug interactions on the development of ulceration has yet to be determined in a daily clinical setting. The aim of the present study was to estimate the potential risks for peptic ulcer presented by co-medication in Japanese RA outpatients on long-term NSAID treatment. Methods: Our hospital-based cohort study enrolled 196 consecutive RA outpatients on NSAID medication for at least three months. The incidence of peptic ulcer was determined by esophagogastroduodenoscopy (EGD) from February 2003 to June 2006. Potential risk factors for developing peptic ulcer were evaluated by univariate and multivariate analysis. Results: Peptic ulcer was found in 43 (21.9%) out of 196 RA outpatients on long-term NSAID treatment. Peptic ulcer incidence was 31% with bisphosphonate co-therapy and 17% without co-therapy. peptic ulcer incidence was only 5% in subjects with proton pump inhibitors (PPI) or prostaglandin E1 analogs (PG) co-therapy, 14% with histamine-H2 receptor antagonists (H2RA) co-therapy, and 28% without anti-ulcer agents. In multivariate logistic regression analysis, bisphosphonate co-therapy remained a significant risk factor for peptic ulcer (OR, 2.36 versus non-users; 95% CI, 1.12-4.97; P = 0.024). Other risk factors for ulcer development were advanced age greater than 60 years and smoking (OR, 2.58; 95% CI, 1.03-6.48; P = 0.043 and OR, 2.72; 95% CI, 1.13-5.54; P = 0.026, respectively.) Factors that significantly reduced the incidence of ulceration were H2RA and PPI/PG co-therapies (OR, 0.33; 95% CI, 0.12-0.88; P = 0.027 and 0.09; 95% CI, 0.01-0.86; P = 0.037, respectively.) Conclusions: Bisphosphonate co-therapy was found to be a significant risk factor in peptic ulcer, while standard-dose H2RA as well as PPI/PG co-therapies proved effective in preventing gastroduodenal injuries in Japanese RA patients on long-term NSAID treatment.