Months 0–3 | Months 0–6 | |||
Tofacitinib 5 mg BID (N=136) | Placebo (N=68) | Tofacitinib 5 mg BID (N=136) | Placebo→ tofacitinib 5 mg BID (N=68) | |
All treatment-emergent AEs | 93 (68.4) | 51 (75.0) | 111 (81.6) | 60 (88.2) |
Serious AEs† | 0 | 3 (4.4) | 2 (1.5) | 5 (7.4) |
Discontinued from study due to AEs | 3 (2.2)‡ | 6 (8.8)‡ | 4 (2.9)‡ | 6 (8.8)‡ |
Death | 0 | 1 (1.5)§ | 0 | 1 (1.5)§ |
AEs of special interest | ||||
Serious infections¶ | 0 | 1 (1.5) | 1 (0.7) | 4 (5.9) |
Herpes zoster (non-serious/serious) | 0 | 0 | 1 (0.7)** | 1 (1.5)** |
Malignancies excluding NMSC†† | 0 | 0 | 1 (0.7)‡‡ | 0 |
NMSC†† | 0 | 0 | 0 | 0 |
Opportunistic infections†† | 0 | 0 | 0 | 0 |
MACE†† | 0 | 0 | 0 | 0 |
GI perforations†† | 0 | 0 | 0 | 0 |
Thromboembolisms (DVT,†† PE,†† ATE) | 0 | 0 | 0 | 0 |
Hepatic events | ||||
Hy’s law case or DILI†† | 0 | 0 | 0 | 0 |
Most frequently reported treatment-emergent AEs (≥5% of patients in any treatment group), n (%) | ||||
Upper respiratory tract infection | 25 (18.4) | 7 (10.3) | 36 (26.5) | 7 (10.3) |
Blood CPK increased | 9 (6.6) | 1 (1.5) | 20 (14.7) | 2 (2.9) |
Hyperlipidaemia | 9 (6.6) | 2 (2.9) | 14 (10.3) | 6 (8.8) |
Diarrhoea | 9 (6.6) | 2 (2.9) | 12 (8.8) | 2 (2.9) |
Hepatic function abnormal | 5 (3.7) | 0 | 12 (8.8) | 3 (4.4) |
ALT increased | 7 (5.1) | 4 (5.9) | 11 (8.1) | 5 (7.4) |
AST increased | 6 (4.4) | 2 (2.9) | 11 (8.1) | 4 (5.9) |
Cough | 6 (4.4) | 0 | 11 (8.1) | 0 |
Abdominal discomfort | 9 (6.6) | 1 (1.5) | 9 (6.6) | 2 (2.9) |
Lymphocyte count decreased | 2 (1.5) | 2 (2.9) | 9 (6.6) | 3 (4.4) |
LDL cholesterol increased | 4 (2.9) | 2 (2.9) | 8 (5.9) | 2 (2.9) |
Dizziness | 7 (5.1) | 1 (1.5) | 7 (5.1) | 1 (1.5) |
Leucopenia | 1 (0.7) | 1 (1.5) | 7 (5.1) | 1 (1.5) |
Blood triglycerides increased | 3 (2.2) | 2 (2.9) | 5 (3.7) | 4 (5.9) |
Urinary tract infection | 2 (1.5) | 2 (2.9) | 4 (2.9) | 5 (7.4) |
Red blood cell count decreased | 1 (0.7) | 3 (4.4) | 2 (1.5) | 4 (5.9) |
*All patients who received ≥1 dose of study medication.
†Serious AEs were defined as any untoward medical occurrence at any dose that resulted in death, were life-threatening (immediate risk of death), required inpatient hospitalisation or prolongation of existing hospitalisation, resulted in persistent or significant disability/incapacity, resulted in congenital abnormality/birth defect or were considered to be important medical events.
‡All permanent discontinuations.
§One patient died due to an accident beyond 28 days after the last dose of study treatment; this was not considered treatment-related by the investigator (reported as a serious AE; counted under both month 3 and month 6 data). The exact date of the accident was unknown and therefore imputed as starting at day 1 and ending at day 264 (awareness date of patient death).
¶Up to month 6, the case in the tofacitinib group was upper respiratory tract infection, and the cases in the placebo group were two cases of bronchitis, one case of pneumonia, and one urinary tract infection.
**Non-serious.
††Adjudicated events.
‡‡Lung neoplasm malignant. The patient (male, aged 63 years) had a 40-year smoking history and a history of chronic obstructive pulmonary disease, latent tuberculosis and a right lung nodule. The patient discontinued between month 4 and month 5 owing to rash. A bronchoscopy, conducted between months 6 and 7 due to respiratory symptoms, revealed the lung cancer, which was determined to be possibly related to blinded therapy by the investigator.
AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ATE, arterial thromboembolism; BID, twice daily; CPK, creatine phosphokinase; DILI, drug-induced liver injury; DVT, deep vein thrombosis; GI, gastrointestinal; LDL, low-density lipoprotein; MACE, major adverse cardiovascular events; N, number of evaluable patients; n, number of patients with event; NMSC, non-melanoma skin cancer; PE, pulmonary embolism.