Tofacitinib 5 mg BID | Tofacitinib 10 mg BID | Placebo | |||||||
---|---|---|---|---|---|---|---|---|---|
Non-MTX csDMARD-IRa (n = 208) | MTX-IRb (n = 1147) | bDMARD-IR (n = 270) | Non-MTX csDMARD-IRa (n = 247) | MTX-IRb (n = 1192) | bDMARD-IR (n = 289) | Non-MTX csDMARD-IRa (n = 82) | MTX-IRb (n = 774) | bDMARD-IR (n = 223) | |
TEAEs | |||||||||
n (%) | 146 (70.2) | 825 (71.9) | 201 (74.4) | 174 (70.4) | 860 (72.1) | 210 (72.7) | 35 (42.7) | 414 (53.5) | 131 (58.7) |
CIRc (95% CI) | 118.4 (99.9–139.2) | 190.4 (177.6–203.8) | 311.0 (269.5–357.1) | 136.3 (116.8–158.1) | 193.5 (180.7–206.8) | 371.9 (323.3–425.7) | 264.1 (183.9–367.3) | 294.9 (267.2–324.7) | 429.5 (359.1–509.7) |
SAEs | |||||||||
n (%) | 21 (10.1) | 122 (10.6) | 21 (7.8) | 21 (8.5) | 103 (8.6) | 20 (6.9) | 2 (2.4) | 25 (3.2) | 10 (4.5) |
CIRc (95% CI) | 8.5 (5.2–12.9) | 12.5 (10.4–14.9) | 12.6 (7.8–19.3) | 7.4 (4.6–11.3) | 9.9 (8.1–12.0) | 12.5 (7.6–19.3) | 10.8 (1.3–39.1) | 11.6 (7.5–17.1) | 20.5 (9.8–37.7) |
Discontinuation due to AEs | |||||||||
n (%) | 18 (8.7) | 97 (8.5) | 25 (9.3) | 21 (8.5) | 110 (9.2) | 25 (8.7) | 2 (2.4) | 26 (3.4) | 10 (4.5) |
CIRc (95% CI) | 7.1 (4.2–11.2) | 9.6 (7.8–11.7) | 14.4 (9.3–21.2) | 7.2 (4.5–11.0) | 10.3 (8.5–12.4) | 15.3 (9.9–22.6) | 10.8 (1.3–39.1) | 12.0 (7.8–17.5) | 20.4 (9.8–37.6) |
AESIs | |||||||||
Serious infection event | |||||||||
n (%) | 7 (3.4) | 35 (3.1) | 3 (1.1) | 4 (1.6) | 39 (3.3) | 5 (1.7) | 1 (1.2) | 3 (0.4) | 2 (0.9) |
CIRc (95% CI) | 2.8 (1.1–5.7) | 3.4 (2.4–4.8) | 1.7 (0.4–5.0) | 1.4 (0.4–3.5) | 3.6 (2.6–5.0) | 3.0 (1.0–7.1) | 5.4 (0.1–30.1) | 1.4 (0.3–4.0) | 4.1 (0.5–14.7) |
Opportunistic infection, excluding tuberculosis | |||||||||
n (%) | 1 (0.5) | 1 (0.1) | 0 (0.0) | 0 (0.0) | 6 (0.5) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
CIRc (95% CI) | 0.4 (0.0–2.2) | 0.1 (0.0–0.6) | 0.0 (0.0–2.1) | 0.0 (0.0–1.3) | 0.6 (0.2–1.2) | 0.0 (0.0–2.3) | 0.0 (0.0–19.9) | 0.0 (0.0–1.7) | 0.0 (0.0–7.5) |
Tuberculosis | |||||||||
n (%) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (0.4) | 7 (0.6) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
CIRc (95% CI) | 0.0 (0.0–1.4) | 0.0 (0.0–0.4) | 0.0 (0.0–2.1) | 0.3 (0.0–1.9) | 0.7 (0.3–1.4) | 0.0 (0.0–2.3) | 0.0 (0.0–19.9) | 0.0 (0.0–1.7) | 0.0 (0.0–7.5) |
Herpes zoster (non-serious and serious) | |||||||||
n (%) | 3 (1.4) | 37 (3.2) | 9 (3.3) | 10 (4.0) | 51 (4.3) | 10 (3.5) | 0 (0.0) | 6 (0.8) | 0 (0.0) |
CIRc (95% CI) | 1.2 (0.2–3.5) | 3.7 (2.6–5.1) | 5.3 (2.4–10.0) | 3.5 (1.7–6.4) | 4.9 (3.6–6.4) | 6.3 (3.0–11.6) | 0.0 (0.0–19.9) | 2.8 (1.0–6.0) | 0.0 (0.0–7.5) |
Major adverse cardiovascular eventsd | |||||||||
n (%) | 2 (1.1) | 3 (0.3) | 2 (0.8) | 2 (1.0) | 5 (0.5) | 1 (0.4) | 0 (0.0) | 1 (0.2) | 0 (0.0) |
CIRc (95% CI) | 0.8 (0.1–2.9) | 0.3 (0.1–0.9) | 1.2 (0.1–4.2) | 0.7 (0.1–2.6) | 0.5 (0.2–1.2) | 0.7 (0.0–3.6) | 0.0 (0–41.1) | 0.7 (0.0–3.7) | 0.0 (0.0–8.7) |
Malignancies (excluding non-melanoma skin cancer) | |||||||||
n (%) | 1 (0.5) | 8 (0.7) | 2 (0.7) | 1 (0.4) | 8 (0.7) | 3 (1.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
CIRc (95% CI) | 0.4 (0.0–2.2) | 0.8 (0.3–1.5) | 1.1 (0.1–4.1) | 0.3 (0.0–1.9) | 0.8 (0.3–1.5) | 1.8 (0.4–5.4) | 0.0 (0.0–19.9) | 0.0 (0.0–1.7) | 0.0 (0.0–7.5) |
Deep vein thrombosis | |||||||||
n (%) | 4 (1.9) | 6 (0.5) | 2 (0.7) | 1 (0.4) | 9 (0.8) | 2 (0.7) | 0 (0.0) | 0 (0.0) | 1 (0.4) |
CIRc (95% CI) | 1.6 (0.4–4.0) | 0.6 (0.2–1.3) | 1.1 (0.1–4.1) | 0.3 (0.0–1.9) | 0.8 (0.4–1.6) | 1.2 (0.2–4.4) | 0.0 (0.0–19.9) | 0.0 (0.0–1.7) | 2.0 (0.1–11.3) |
Pulmonary embolism | |||||||||
n (%) | 0 (0.0) | 7 (0.6) | 1 (0.4) | 0 (0.0) | 7 (0.6) | 3 (1.0) | 0 (0.0) | 1 (0.1) | 2 (0.9) |
CIRc (95% CI) | 0.0 (0.00–1.4) | 0.7 (0.3–1.4) | 0.6 (0.0–3.2) | 0.0 (0.0–1.3) | 0.7 (0.3–1.3) | 1.8 (0.4–5.4) | 0.0 (0.0–19.9) | 0.5 (0.0–2.6) | 4.1 (0.5–14.7) |
Deep vein thrombosis or pulmonary embolism | |||||||||
n (%) | 4 (1.9) | 12 (1.0) | 2 (0.7) | 1 (0.4) | 15 (1.3) | 5 (1.7) | 0 (0.0) | 1 (0.1) | 2 (0.9) |
CIRc (95% CI) | 1.6 (0.4–4.0) | 1.2 (0.6–2.1) | 1.1 (0.1–4.1) | 0.3 (0.0–1.9) | 1.4 (0.8–2.3) | 3.1 (1.0–7.1) | 0.0 (0.0–19.9) | 0.5 (0.0–2.6) | 4.1 (0.5–14.7) |
Deep vein thrombosis and pulmonary embolism | |||||||||
n (%) | 0 (0.0) | 1 (0.1) | 1 (0.4) | 0 (0.0) | 1 (0.1) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (0.4) |
CIRc (95% CI) | 0.0 (0.0–1.4) | 0.1 (0.0–0.6) | 0.6 (0.0–3.2) | 0.0 (0.0–1.3) | 0.1 (0.0–0.5) | 0.0 (0.0–2.3) | 0.0 (0.0–19.9) | 0.0 (0.0–1.7) | 2.0 (0.1–11.3) |
Death | |||||||||
n (%) | 1 (0.5) | 9 (0.8) | 2 (0.7) | 1 (0.4) | 3 (0.3) | 0 (0.0) | 0 (0.0) | 1 (0.1) | 0 (0.0) |
CIRc (95% CI) | 0.4 (0.0–2.2) | 0.9 (0.4–1.7) | 1.1 (0.1–4.1) | 0.3 (0.0–1.9) | 0.3 (0.1–0.8) | 0.0 (0.0–2.3) | 0.0 (0.0–19.9) | 0.5 (0.0–2.6) | 0.0 (0.0–7.5) |