Publications

Historically, patients with RA have suffered with upper tract gastrointestinal perforation (GIPs), associated with NSAID use. More recently, the IL-6 receptor antagonist tocilizumab (TCZ) has been associated with lower tract GIPs. Janus kinase (JAK) inhibitors, including tofacitinib (TOF), with some downstream effects on IL-6 signalling, also have potential for an increased risk of GIPs.There is limited real-world evidence and almost no comparative evidence on the risk for GIP associated with TCZ or TOF. A real-world dataset (from Medicare [2006–2013] and the US longitudinal database Marketscan [2010–2014]) was analysed to examine risks for GIP. TNFi therapy was the referent since it was the most commonly used biologic RA therapy. The primary outcome of interest was hospitalised GIP.After multivariable adjustment for confounding factors including age, sex, co-morbidities (including diabetes, peptic ulcer disease, gastro-esophageal reflux disease, diverticulitis, and other gastro-intestinal conditions), other medications and number of biologics used, lower tract GIP risk was significantly elevated for both TCZ and TOF versus TNF inhibitors (HRs=TCZ, 2.55, 95% CI 1.33–4.88; TOF, 3.24, 95% CI 1.05–10.04). Most perforation cases occurred in the lower GI tract (62% overall); the incidence of upper tract GIPs was similar among TOF and all biologics. Despite being statistically significant, the differences between RA treatments were relatively small, approximately 1 per 1000 patient years.Exposure risk may be a concern among selected patients: older patients, those withco-morbidities including diverticulitis/other GI conditions and prednisone dose ≥7.5 mg per day, since these were other factors associated with lower tract GIPs.