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


CONCLUSIONS
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.
Chan
Francis K L
FK
The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong. fklchan@cuhk.edu.hk
Cryer
Byron
B
Goldstein
Jay L
JL
Lanas
Angel
A
Peura
David A
DA
Scheiman
James M
JM
Simon
Lee S
LS
Singh
Gurkirpal
G
Stillman
Martin J
MJ
Wilcox
Charles M
CM
Berger
Manuela F
MF
Breazna
Aurora
A
Dodge
William
W
D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology; D005767:Gastrointestinal Diseases / Q000139:chemically induced*; D041981:Gastrointestinal Tract / Q000033:anatomy & histology / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D016032:Randomized Controlled Trials as Topic; D012107:Research Design
D000894:Anti-Inflammatory Agents, Non-Steroidal