Table 5.

Incidence of adverse events after randomization according to celecoxib dose, stratified by UGT1A6 genotypea

PlaceboCelecoxib, 200 mg twice dailyCelecoxib, 400 mg twice daily
All genotypes, no. at risk550547543
Cardiovascular disorders, no. of eventsb243440
 Cumulative incidence, 3 y, % ± SE5.2 ± 1.17.4 ± 1.38.9 ± 1.4
 RR (95% CI)1.01.41 (0.83–2.37)1.66 (1.00–2.76)
Renal and hypertensive disorders, no. of eventsc9712497
Cumulative incidence, 3 y, % ± SE19.9 ± 1.925.8 ± 2.120.3 ± 1.9
 RR (95% CI)1.01.35 (1.03–1.76)1.01 (0.76–1.33)
 Gastrointestinal ulceration/hemorrhage, no. of eventsd575754
 Cumulative incidence, 3 y, % ± SE12.0 ± 1.612.0 ± 1.611.5 ± 1.5
 RR (95% CI)1.00.98 (0.68–1.42)0.94 (0.65–1.36)
Patients with wild-type genotypes, no. at risk239232241
Cardiovascular disorders, no. of eventsb111321
 Cumulative incidence, 3 y, % ± SE5.6 ± 1.66.1 ± 1.810.1 ± 2.2
 RR (95% CI)1.01.14 (0.51–2.55)1.81 (0.87–3.75)
Renal and hypertensive disorders, no. of eventsc325449
 Cumulative incidence, 3 y, % ± SE15.3 ± 2.626.8 ± 3.222.9 ± 3.1
 RR (95% CI)1.01.87 (1.21–2.89)1.50 (0.96–2.34)
Gastrointestinal ulceration/hemorrhage, no. of eventsd232617
 Cumulative incidence, 3 y, % ± SE12.4 ± 2.512.2 ± 2.48.3 ± 2.0
 RR (95% CI)1.01.14 (0.65–2.00)0.68 (0.36–1.27)
Patients with variant genotypes, no. at risk311315302
Cardiovascular disorders, no. of eventsb132119
 Cumulative incidence, 3 y, % ± SE4.8 ± 1.48.4 ± 1.87.9 ± 1.8
 RR (95% CI)1.01.61 (0.81–3.22)1.52 (0.75–3.08)
Renal and hypertensive disorders, no. of eventsc657048
 Cumulative incidence, 3 y, % ± SE23.3 ± 2.725.1 ± 2.718.3 ± 2.5
 RR (95% CI)1.01.10 (0.79–1.54)0.76 (0.52–1.10)
Gastrointestinal ulceration/hemorrhage, no. of eventsd343137
 Cumulative incidence, 3 y, % ± SE11.7 ± 2.011.9 ± 2.114.1 ± 2.2
 RR (95% CI)1.00.88 (0.54–1.43)1.10 (0.69–1.76)
  • aWild-type UGT1A6 genotypes include individuals with no T181A or R184S alleles. Variant UGT1A6 genotypes include individuals with ≥1 variant (T181 or R184S) allele. Adverse events include those that were reported during the time after the first dose of the study drug until 30 days after the last dose of study drug. The analysis excludes 7 participants with genotype information who were randomized but never initiated treatment: 3 patients in the placebo group, 2 assigned to 200 mg of celecoxib twice daily, and 2 assigned to 400 mg of celecoxib twice daily. Data on adverse events include events reported among 639 patients who continued blinded treatment beyond the 36-month core phase of the study who were enrolled in the 24-month extension study.

  • bCardiovascular events include cardiovascular death or circulatory collapse, stroke, myocardial infarction, congestive heart failure, venous thrombosis or thromboembolism, cardiovascular therapeutic procedures, vascular therapeutic procedures, cerebrovascular disease, and vascular disease.

  • cRenal and hypertensive events include elevated creatinine, fluid retention or edema, hypertension, proteinuria, and renal failure.

  • dGastrointestinal ulceration and hemorrhage events include anemia, gastrointestinal bleeding, gastritis/duodenitis, upper or lower gastrointestinal ulceration, and other hemorrhage.