Incidence rates (patients with event per 100 patient-years; 95% CI) for safety events of special interest in bDMARD-naive versus bDMARD-IR subpopulations in the P3 cohort
| bDMARD-naive | bDMARD-IR | |||||
|---|---|---|---|---|---|---|
| Safety event, incidence rate (patients with event per 100 patient-years; 95% CI) | Placebo N=465 | Tofacitinib 5 mg twice daily N=893 | Tofacitinib 10 mg twice daily N=898 | Placebo N=181 | Tofacitinib 5 mg twice daily N=247 | Tofacitinib 10 mg twice daily N=241 |
| Exposure, patient-years | 149.5 | 885.5 | 917.4 | 42.5 | 170.5 | 154.8 |
| All SAEs | 15.0 (9.9 to 22.7) | 12.2 (10.0 to 14.8) | 9.6 (7.8 to 11.9) | 19.0 (9.5 to 38.0) | 13.0 (8.5 to 20.0) | 11.3 (7.0 to 18.1) |
| Discontinuations due to AEs | 10.1 (6.1 to 16.7) | 9.1 (7.3 to 11.3) | 9.6 (7.8 to 11.9) | 18.9 (9.5 to 37.8) | 14.8 (10.0 to 21.9) | 15.0 (10.0 to 22.5) |
| All serious infections | 2.0 (0.6 to 6.2) | 3.4 (2.4 to 4.9) | 3.5 (2.5 to 4.9) | 0 | 2.3 (0.9 to 6.3) | 3.2 (1.3 to 7.8) |
| Herpes zoster (all—serious and non-serious) | 2.0 (0.7 to 6.3) | 4.0 (2.8 to 5.5) | 4.4 (3.2 to 6.0) | 0 | 5.4 (2.8 to 10.4) | 5.4 (2.7 to 10.7) |
| Herpes zoster (serious) | 0 | 0.3 (0.1 to 1.1) | 0.3 (0.1 to 1.0) | 0 | 0.6 (0.1 to 4.2) | 0 |
| Herpes zoster (non-serious) | 2.0 (0.7 to 6.3) | 3.6 (2.5 to 5.1) | 4.1 (3.0 to 5.7) | 0 | 4.8 (2.4 to 9.6) | 5.4 (2.7 to 10.7) |
| Tuberculosis | 0 | 0 | 0.8 (0.4 to 1.6) | 0 | 0 | 0 |
| Opportunistic infections (excluding tuberculosis) | 0 | 0.3 (0.1 to 1.1) | 0.4 (0.2 to 1.2) | 0 | 0 | 0 |
| Malignancy (excluding NMSC) | 0 | 0.6 (0.2 to 1.4) | 0.9 (0.4 to 1.7) | 0 | 1.2 (0.3 to 4.7) | 1.9 (0.6 to 6.0) |
| Lymphoma/lymphoproliferative disorders | 0 | 0 | 0.1 (0.0 to 0.8) | 0 | 0 | 0.6 (0.1 to 4.6) |
| MACE | 1.3 (0.3 to 5.4) | 0.6 (0.2 to 1.4) | 0.8 (0.4 to 1.6) | 0 | 1.2 (0.3 to 4.7) | 0.6 (0.1 to 4.6) |
| All cause mortality (30-day rule)* | 0.7 (0.1 to 4.7) | 0.6 (0.2 to 1.4) | 0.4 (0.2 to 1.2) | 0 | 1.2 (0.3 to 4.7) | 0 |
*30-day rule: deaths occurring within 30 days of the last dose.
Safety was assessed during months 0–6 for the placebo group and months 0–24 for the tofacitinib groups. Patients who advanced from placebo to tofacitinib are counted in the placebo group until advancement in the various studies—some patients advanced at month 3, while others advanced at month 6 unless they did not achieve a 20% improvement in swollen/tender joint counts at month 3, in which case they advanced to active treatment (ORAL Sync, ORAL Scan and ORAL Standard).
bDMARD, biological disease-modifying antirheumatic drug; IR, inadequate responders; MACE, major adverse cardiac events; N, number of patients included in analysis; NMSC, non-melanoma skin cancer; P3, phase III; SAE, serious adverse event.