Table 2.
AEs by treatment group and background MTX dose (up to month 3)
| MTX dose: ≤ 15 mg/week | MTX dose: > 15 mg/week | |||||
|---|---|---|---|---|---|---|
| Tofacitinib 5 mg BID (n = 116) | Tofacitinib 10 mg BID (n = 122) | Placebo (n = 133) | Tofacitinib 5 mg BID (n = 70) | Tofacitinib 10 mg BID (n = 56) | Placebo (n = 59) | |
| Treatment emergent AEs, n (%) | ||||||
| Any AE | 49 (42.2) | 60 (49.2) | 49 (36.8) | 38 (54.3) | 23 (41.1) | 25 (42.4) |
| Serious AEs | 2 (1.7) | 2 (1.6) | 1 (0.8) | 1 (1.4) | 2 (3.6) | 3 (5.1) |
| Severe AEs | 2 (1.7) | 3 (2.5) | 1 (0.8) | 1 (1.4) | 2 (3.6) | 3 (5.1) |
| Discontinued due to AEs | 2 (1.7) | 6 (4.9) | 2 (1.5) | 0 | 1 (1.8) | 3 (5.1) |
| Dose reduction or temporary discontinuation due to AEs | 5 (4.3) | 19 (15.6) | 11 (8.3) | 7 (10.0) | 6 (10.7) | 5 (8.5) |
| Reported AEs by system organ class | ||||||
| Infections and infestations, n (%) | ||||||
| Upper respiratory tract infection | 6 (5.2) | 6 (4.9) | 4 (3.0) | 4 (5.7) | 2 (3.6) | 5 (8.5) |
| Nasopharyngitis | 7 (6.0) | 8 (6.6) | 3 (2.3) | 3 (4.3) | 1 (1.8) | 2 (3.4) |
| Urinary tract infection | 1 (0.9) | 3 (2.5) | 3 (2.3) | 2 (2.9) | 1 (1.8) | 0 |
| Bronchitis | 1 (0.9) | 3 (2.5) | 0 | 3 (4.3) | 0 | 0 |
| Sinusitis | 3 (2.6) | 2 (1.6) | 1 (0.8) | 0 | 1 (1.8) | 0 |
| Laryngitis | 1 (0.9) | 0 | 1 (0.8) | 0 | 1 (1.8) | 0 |
| Pharyngitis | 0 | 4 (3.3) | 2 (1.5) | 1 (1.4) | 1 (1.8) | 0 |
| Lower respiratory tract infection | 0 | 2 (1.6) | 0 | 0 | 0 | 1 (1.7) |
| Gastrointestinal disorders, n (%) | ||||||
| Diarrhea | 3 (2.6) | 4 (3.3) | 1 (0.8) | 3 (4.3) | 2 (3.6) | 0 |
| Nausea | 3 (2.6) | 1 (0.8) | 3 (2.3) | 1 (1.4) | 1 (1.8) | 1 (1.7) |
| Abdominal pain | 2 (1.7) | 2 (1.6) | 1 (0.8) | 1 (1.4) | 0 | 0 |
| Dyspepsia | 3 (2.6) | 0 | 1 (0.8) | 1 (1.4) | 0 | 1 (1.7) |
| Constipation | 1 (0.9) | 1 (0.8) | 2 (1.5) | 1 (1.4) | 1 (1.8) | 0 |
| Musculoskeletal and connective tissue disorders, n (%) | ||||||
| Psoriatic arthropathy | 2 (1.7) | 0 | 2 (1.5) | 2 (2.9) | 0 | 1 (1.0) |
| Investigations, n (%) | ||||||
| Blood creatine phosphokinase increased | 1 (0.9) | 2 (1.6) | 0 | 0 | 0 | 1 (1.7) |
| Nervous system disorders, n (%) | ||||||
| Headache | 2 (1.7) | 7 (5.7) | 5 (3.8) | 4 (5.7) | 6 (10.7) | 4 (6.8) |
| Dizziness | 2 (1.7) | 0 | 2 (1.5) | 2 (2.9) | 0 | 1 (1.7) |
| Respiratory, thoracic, and mediastinal disorders, n (%) | ||||||
| Cough | 2 (1.7) | 0 | 2 (1.5) | 1 (1.4) | 1 (1.8) | 3 (5.0) |
| Skin and subcutaneous tissue disorders, n (%) | ||||||
| Psoriasis | 2 (1.7) | 0 | 0 | 0 | 1 (1.8) | 0 |
| AEs of special interest (up to month 6) | ||||||
| Malignancies, n (%) | ||||||
| Bladder cancer | 1 (0.9) | 0 | 0 | 0 | 0 | 0 |
| Vulvar cancer | 1 (2.0) | 0 | 0 | 0 | 0 | 0 |
| Basal cell NMSC | 0 | 0 | 0 | 0 | 1 (1.8) | 0 |
| Serious infections, n (%) | 1 (0.9) | 3 (2.5) | 0 | 0 | 0 | 0 |
| Herpes zoster, n (%) | 1 (0.9) | 1 (0.8) | 0 | 1 (1.4) | 1 (1.8) | 0 |
| Total MACE, n (%) | 0 | 0 | 0 | 0 | 0 | 0 |
| Total VTE, n (%) | 0 | 0 | 0 | 0 | 0 | 0 |
This analysis included all patients who received MTX as background therapy only on day 1 in the safety analysis set. Eight patients who used both MTX and other csDMARDs on day 1 were excluded, as were two patients who exceeded the protocol-defined maximum dose of MTX for the analysis (20 mg/week), and one patient without dosing frequency to calculate the dose
All AEs that were treatment-emergent were reported
AE, adverse event; BID, twice daily; csDMARD, conventional synthetic disease-modifying anti-rheumatic drug; MACE, major adverse cardiovascular event; MTX, methotrexate or methotrexate sodium; n, number of patients; NMSC, non-melanoma skin cancer; SAE, serious adverse event; VTE, venous thromboembolism