Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Safety without Borders: Upper and Lower Gastrointestinal Safety of Celecoxib in a Pooled Analysis of 52 Prospective, Randomised, Double-Blinded, Parallel-Group Clinical Trials.
Singh3, Gurkirpal, Triadafilopoulos3, George, Agrawal1, Naurang, Makinson2, Geoff, Li2, Chunming, Nguyen2, Ha
Nonsteroidal anti-inflammatory drug (NSAID)-related serious upper and lower gastrointestinal (UGI/LGI) complications are well-recognized, but most clinical trials of cyclooxygenase (COX)-2 selective NSAIDs have focused on UGI outcomes as their primary endpoints. We used a novel composite endpoint measuring injury in the entire GI tract to study GI outcomes in patients enrolled in celecoxib clinical trials using individual patient-level data.
Aims & Methods:
A novel endpoint clinically-significant upper and lower GI events (CSULGIEs) was developed. A total of 52 randomized, double-blind, parallel group studies were identified from the Celecoxib Clinical Database and included in this patient-level pooled analysis. All studies had a planned duration of continuous treatment with celecoxib and either a nsNSAID (ibuprofen, naproxen, diclofenac, ketoprofen, loxoprofen), rofecoxib or a placebo comparator arm for >= than 4 weeks. All included studies had their final study reports completed by October 1st, 2007. Open-label and cross-over trials, and all healthy volunteer studies were excluded from the analysis. The primary endpoint was the cumulative incidence of CSULGIEs (including perforations, obstructions, clinically significant bleeds) or symptomatic ulcers as adjudicated by an independent blinded committee. Adjudication was based on predefined criteria and available reported adverse events, laboratory data and narratives. The stratified log rank test was used to compare treatments, adjusting for studies. All doses of celecoxib (from <200 to 800 mg total daily dose) and nsNSAIDS were pooled. Asymptomatic hemoglobin or hematocrit drops were not considered as cases for this analysis.
A total of 51,048 patients were included in the study: 28,614 patients were randomized to celecoxib (mean age 60.1 years), 15,278 to nsNSAIDs (mean age 59.3 years), 1,329 to rofecoxib (mean age 70.6 years) and 5,827 to placebo (mean age 57.2 years). A total of 354 cases of serious UGI/LGI complications were reviewed by the adjudication committee who confirmed 92 CSULGIEs. The number of events and the incidence rate per 100 person-years were: celecoxib [40, 0.33%], nsNSAID [38, 0.82%], rofecoxib  and placebo [14, 0.37%]). The difference between celecoxib and nsNSAIDs was statistically significant, using Kaplan Meier stratified log-rank test (p<0.0015).
The known UGI safety of celecoxib is also associated with a lower risk of all clinically significant GI events throughout the entire GI tract compared to patients treated with nsNSAIDs.
To cite this abstract, please use the following information:
Singh, Gurkirpal, Triadafilopoulos, George, Agrawal, Naurang, Makinson, Geoff, Li, Chunming, Nguyen, Ha; Safety without Borders: Upper and Lower Gastrointestinal Safety of Celecoxib in a Pooled Analysis of 52 Prospective, Randomised, Double-Blinded, Parallel-Group Clinical Trials. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2205