title: Incidence of Gastrointestinal Perforations in Patients with Rheumatoid Arthritis Treated with Tocilizumab from Clinical Trial, Postmarketing, and Real-World Data Sources.
abstract: BACKGROUND
  The aim of this study was to use multiple data sources to update information on gastrointestinal perforations (GIPs) during tocilizumab (TCZ) treatment in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  Reporting rates of GIP events were estimated from three distinct patient data sets: a TCZ-IV RA clinical trial all-exposure population, a global TCZ postmarketing safety database population, and a US healthcare claims database population of patients with RA, including patients who received TCZ, anti-tumor necrosis factor (aTNF) agents, or abatacept.
  
  
  RESULTS
  The clinical trial, global postmarketing, and healthcare claims populations provided 17,906, 382,621, and 3268 patient-years (PYs) of TCZ exposure, respectively. GIP incidence rates [95% confidence interval (CI)] were 1.9 (1.3-2.7), 1.2 (1.1-1.3), and 1.8 (0.7-4.0; specific definition) to 2.8 (1.3-5.2; sensitive definition) per 1000 PYs for the clinical trial, postmarketing, and healthcare claims populations, respectively. The GIP incidence rate (95% CI) for the comparator aTNF healthcare claims population ranged from 0.6 (0.3-1.2) to 0.9 (0.5-1.5) per 1000 PYs, for an absolute rate difference between TCZ and aTNFs of 1.2 (-0.3 to 2.5) to 1.9 (0.0-3.7) per 1000 PYs, corresponding to a number needed to harm between 533 and 828.
  
  
  CONCLUSIONS
  The TCZ GIP event rates from multiple data sources were consistent with previously reported rates, did not increase over time, and were significantly associated with the number of prior biologics. Comparison of GIP incidence rates among patients with prior biologic exposure suggests that, for every 1000 patients treated with TCZ per year, an additional 1-2 GIP events might occur compared with patients treated with aTNFs.
  
  
  BACKGROUND
  Roche.
authors.affiliation: Genentech, Inc., South San Francisco, CA, USA. monemis@gene.com.
authors.forename: Sharareh
authors.initials: S
authors.lastname: Monemi
authors.affiliation: Genentech, Inc., South San Francisco, CA, USA.
authors.forename: Erhan
authors.initials: E
authors.lastname: Berber
authors.affiliation: Genentech, Inc., South San Francisco, CA, USA.
authors.forename: Khaled
authors.initials: K
authors.lastname: Sarsour
authors.affiliation: Roche Products Ltd., Welwyn Garden City, Hertfordshire, UK.
authors.forename: Jianmei
authors.initials: J
authors.lastname: Wang
authors.affiliation: Genentech, Inc., South San Francisco, CA, USA.
authors.forename: Kathy
authors.initials: K
authors.lastname: Lampl
authors.affiliation: Genentech, Inc., South San Francisco, CA, USA.
authors.forename: Kamal
authors.initials: K
authors.lastname: Bharucha
authors.affiliation: F. Hoffmann-La Roche, Basel, Switzerland.
authors.forename: Attila
authors.initials: A
authors.lastname: Pethoe-Schramm
keywords: Gastrointestinal perforation; Rheumatoid arthritis; Tocilizumab