Table 3.
Risk of Adenoma According to Celecoxib Dose, Stratified by CYP2C9 Genotypea
| Placebo |
Celecoxib, 200 mg Twice Daily |
Celecoxib, 400 mg Twice Daily |
|
|---|---|---|---|
| All patients, No. at risk.b | 499 | 498 | 500 |
| Cumulative incidence, 3 yrs, % ± SE | 60.5 ± 2.3 | 42.5 ± 2.3 | 36.9 ± 2.2 |
| RR (95% CI) compared with placeboc | 1.0 | 0.65 (0.56–0.76) | 0.54 (0.46–0.63) |
| P valued | -- | <.001 | <.001 |
| RR (95% CI) compared with 200 mge | -- | 1.0 | 0.82 (0.69–0.98) |
| P valuef | -- | -- | .03 |
|
| |||
| By genotype | |||
| Patients with wild-type genotypes, No. at riskb | 338 | 330 | 328 |
| Cumulative incidence, 3 yrs, % ± SE | 57.2 ± 2.8 | 39.9 ± 2.8 | 37.0 ± 2.8 |
| RR (95% CI) compared with placeboc | 1.0 | 0.64 (0.53- 0.77) | 0.56 (0.46–0.68) |
| P valued | -- | <.001 | <.001 |
| RR (95% CI) compared with 200 mge | -- | 1.0 | 0.89 (0.72, 1.11) |
| P valuef | -- | -- | 0.31 |
| Patients with CYP2C9*2 genotypes, No. at riskb | 111 | 99 | 108 |
| Cumulative incidence, 3 yrs, % ± SE | 68.4 ± 4.6 | 46.0 ± 5.3 | 41.0 ± 4.9 |
| RR (95% CI) compared with placeboc | 1.0 | 0.63 (0.47–0.86) | 0.54 (0.40–0.74) |
| P valued | -- | .003 | <.001 |
| RR (95% CI) compared with 200 mge | -- | 1.0 | 0.83 (0.57–1.21) |
| P valuef | -- | -- | .33 |
| Patients with CYP2C9*3 genotypes, No. at riskb | 50 | 69 | 64 |
| Cumulative incidence, 3 yrs, % ± SE | 64.6 ± 7.0 | 49.3 ± 6.2 | 29.6 ± 5.9 |
| RR (95% CI) compared with placeboc | 1.0 | 0.76 (0.51–1.13) | 0.41 (0.24–0.70) |
| P valued | -- | 0.18 | <.001 |
| RR (95% CI) compared with 200 mge | -- | 1.0 | 0.51 (0.30–0.87) |
| P valuef | -- | -- | .01 |
Wild-type genotypes include individuals with no *2 (R144C) or *3 (I359L) alleles. CYP2C9*2 genotypes include individuals with ≥ one *2 allele. CYP2C9*3 genotypes include individuals with ≥ one *3 allele. Individuals with one *2 allele and one *3 allele were classified as having CYP2C9*3 genotypes.
No. at risk include patients who underwent a follow-up colonoscopy at year 1 and/or year 3.
Relative risk calculated by the Mantel-Cox test, with stratification for aspirin use, time, age and sex, with the placebo group as the referent group.
The p value is the Cochran-Mantel-Haenszel test of general association compared to the placebo group.
Relative risk calculated by the Mantel-Cox test, with stratification for aspirin use, time, age and sex, with the celecoxib 200 mg twice daily group as the referent group.
The p value is the Cochran-Mantel-Haenszel test of general association compared to celecoxib 200 mg twice daily group.