A novel composite endpoint to evaluate the gastrointestinal (GI) effects of nonsteroidal antiinflammatory drugs through the entire GI tract

J Rheumatol. 2010 Jan;37(1):167-74. doi: 10.3899/jrheum.090168. Epub 2009 Nov 2.

Abstract

Objective: Nonsteroidal antiinflammatory drugs (NSAID) not only cause damage to the upper gastrointestinal (GI) tract but also affect the lower GI tract. To date, there is no endpoint that evaluates serious GI events in the entire GI tract. The objective of this report is to introduce a novel composite endpoint that measures damage to the entire GI tract - clinically significant upper and lower GI events (CSULGIE) - in patients with NSAID-induced GI damage.

Methods: We reviewed the data from largescale, multicenter, randomized, clinical trials on lower GI toxicity associated with NSAID use. The rationale for using CSULGIE as a primary endpoint in 2 ongoing trials - the Celecoxib vs Omeprazole and Diclofenac for At-risk Osteoarthritis (OA) and Rheumatoid Arthritis (RA) Patients (CONDOR) trial and the Gastrointestinal Randomized Events and Safety Open-Label NSAID Study (GI-REASONS) - is also discussed.

Results: Previous randomized trials focused primarily on damage to the upper GI tract and often neglected the lower GI tract. The CSULGIE endpoint extends the traditional "perforation, obstruction, and bleeding" assessment of upper GI complications by including events in the lower GI tract (small/large bowel) such as perforation, bleeding, and clinically significant anemia.

Conclusion: By providing clinicians with a new, descriptive language for adverse events through the entire GI tract, the CSULGIE endpoint has the potential to become a standard tool for evaluating the GI effects of a range of therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal* / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal* / pharmacology
  • Gastrointestinal Diseases / chemically induced*
  • Gastrointestinal Tract / anatomy & histology
  • Gastrointestinal Tract / drug effects*
  • Humans
  • Middle Aged
  • Multicenter Studies as Topic
  • Randomized Controlled Trials as Topic
  • Research Design

Substances

  • Anti-Inflammatory Agents, Non-Steroidal