Factors associated with gastrointestinal perforation in a cohort of patients with rheumatoid arthritis

Abstract

Objective To estimate the incidence and risk factors for gastrointestinal (GI) perforation among patients with rheumatoid arthritis (RA). Methods Claims from employer health insurance plans were used to identify RA patients and those hospitalized for upper or lower GI perforation. GI perforation cases were identified using both a sensitive and specific definition. A Cox model using fixed and time-varying covariates was used to evaluate risk of GI perforation. Results Among 143,433 RA patients, and using a maximally sensitive GI perforation definition, 696 hospitalizations with perforation were identified. The rate of perforation was 1.70 per 1000 person years (PYs) [95% CI, 1.58–1.83] and most perforations (83%) occurred in the lower GI tract. The rate of perforation was lower when a more specific GI perforation definition was used (0.87, 95% CI, 0.78–0.96 per 1,000 PYs). Age and diverticulitis were among the strongest risk factors for perforation (diverticulitis hazard ratio=14.5 [95% CI, 11.8–17.7] for more sensitive definition, hazard ratio=3.9 [95% CI, 2.5–5.9] for more specific definition). Among various RA medication groups, and compared to methotrexate, the risk of GI perforation was highest among patients with exposure to concomitant non-biologic disease-modifying antirheumatic drugs and glucocorticoids. Biologics without glucocorticoid exposure was not a risk factor for perforation. Conclusion GI perforation is a rare but serious condition that affects patients with RA, most frequently in the lower GI tract. Clinicians should be aware of risk factors for GI perforation when managing RA patients, including age, history of diverticulitis, and use of glucocorticoids or NSAIDs.

Safety and Efficacy of Tofacitinib, an Oral Janus Kinase Inhibitor, for the Treatment of Rheumatoid Arthritis in Open-label, Longterm Extension Studies

“…The IR for GI perforation in patients treated with tofacitinib [0.13 (95% CI: 0.07-0.24) events per 100 patient-yrs] was consistent with the previously published background rates for patients receiving biologic and nonbiologic DMARD (0.05 to 0.17 events per 100 patient-yrs 50,51 ). The safety reported here relates only to findings in the LTE phase of the tofacitinib development program, with the exception of GI perforations, where an integrated analysis is presented (the majority of cases occurred in LTE studies).…”

Safety of synthetic and biological DMARDs: a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis

“…These focused on diverse outcomes: 22 on infections,11–32 12 on cancer,33–44 5 on mortality,45–49 3 on neurological events,50–52 2 on cardiovascular events,53 54 2 on gastrointestinal perforations,55 56 1 on venous thrombotic events,57 1 on elevation of liver enzymes,58 and 1 on new-onset psoriasis 59. From the 22 studies on infections, 9 addressed serious infections,11–19 5 skin infections20–24 (mainly infection by herpes zoster), 4 tuberculosis25–28 and 4 other types of infections 29–32.…”

Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2012: Table 1

“…The concomitant use of corticosteroids and NSAIDs may increase the risk of these events. TCZ should be used with caution in patients with a history of intestinal ulceration or diverticulitis (category D evidence210 211). …”

“…This was not found for etanercept. Acute phase reactions correlate with response (category B/C/D evidence207 210 211 214 410–412). …”