Table 4

Summary of safety up to week 16 and up to week 48

Patients with events, n (%)Up to week 16
(double-blind phase)
Up to week 48
(double-blind and open-label phases)
5 mg two times per day
5 mg two times per day
Placebo→ tofacitinib
5 mg two times per day
AEs73 (54.9)70 (51.5)103 (77.4)93 (68.4)
SAEs*2 (1.5)1 (0.7)7 (5.3)2 (1.5)
Severe AEs†2 (1.5)06 (4.5)0
Discontinued study drug due to AEs3 (2.3)1 (0.7)8 (6.0)3 (2.2)
Reduced dose or temporarily discontinued study drug due to AEs9 (6.8)5 (3.7)18 (13.5)13 (9.6)
Most common AEs by preferred term (>5% of any treatment group)
 Upper respiratory tract infection14 (10.5)10 (7.4)21 (15.8)18 (13.2)
 Nasopharyngitis9 (6.8)10 (7.4)11 (8.3)17 (12.5)
 Diarrhoea6 (4.5)5 (3.7)10 (7.5)8 (5.9)
 Arthralgia1 (0.8)8 (5.9)2 (1.5)9 (6.6)
 ALT increased4 (3.0)1 (0.7)8 (6.0)2 (1.5)
 Protein urine present5 (3.8)2 (1.5)8 (6.0)4 (2.9)
 Headache2 (1.5)3 (2.2)5 (3.8)7 (5.1)
 Abdominal pain upper04 (2.9)2 (1.5)7 (5.1)
 Malignancies (including NMSC)‡0000
 Thromboembolic events (DVT, PE or ATE)‡0000
 GI perforation‡0000
 Hepatic events‡1 (0.8)§03 (2.3)¶0
 HZ (serious and non-serious)003 (2.3)**2 (1.5)**
 Opportunistic infections‡0000
 Serious infections1 (0.8)††01 (0.8)††0
Laboratory values meeting protocol criteria for monitoring‡‡06 (4.4)7 (5.3)10 (7.4)
 Haemoglobin drop >20 g/L below baseline04 (2.9)3 (2.3)5 (3.7)
 Platelet count <100×109/L01 (0.7)01 (0.7)
 Serum creatinine increase >50% or increase 0.5 mg/dL over the average of screening and baseline values004 (3.0)3 (2.2)
 Creatine kinase >5×ULN01 (0.7)01 (0.7)
Laboratory values meeting protocol criteria for discontinuation of study drug§§1 (0.8)02 (1.5)0
 Two sequential AST or ALT elevations >5×ULN1 (0.8)02 (1.5)0
  • Data are from the week 48 final analysis.

  • *SAEs were defined as any untoward medical occurrence at any dose that was life-threatening; resulted in hospitalisation, prolongation of existing hospitalisation, persistent or significant disability/incapacity, congenital anomaly/birth defect or death; or was considered to be an important medical event.

  • †Investigators used the adjectives mild, moderate or severe to describe the maximum intensity of the AE. Severe AEs were defined as those that interfered significantly with the patient’s usual function.

  • ‡Adjudicated events.

  • §Two sequential AST or ALT ≥3×ULN; unrelated DILI; patient did not meet criteria for potential Hy’s law or definite Hy’s law.

  • ¶One patient had two sequential AST or ALT ≥3×ULN, which was unrelated DILI; one patient had AST or ALT ≥5×ULN, which was unlikely DILI; one patient had cholecystitis and recurrence of gallstones, which was unrelated DILI. None of these patients met the criteria for potential Hy’s law nor definite Hy’s law.

  • **All cases were non-serious.

  • ††Meningitis; did not meet opportunistic infection adjudication criteria.

  • ‡‡Notably, no patients met the following protocol criteria for monitoring: absolute neutrophil count <1.2×109/L; absolute lymphocyte count <0.5×109/L.

  • §§Notably, no patients met the following protocol criteria for discontinuation of study drug: two sequential absolute neutrophil counts <1.0×109/L; two sequential absolute lymphocyte counts <0.5x109/L.

  • AE, adverse event; AESI, adverse event of special interest; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ATE, arterial thromboembolism; DILI, drug-induced liver injury; DVT, deep vein thrombosis; GI, gastrointestinal; HZ, herpes zoster; ILD, interstitial lung disease; N, number of patients in safety analysis set; n, number of patients with event; NMSC, non-melanoma skin cancer; MACE, major adverse cardiovascular events; PE, pulmonary embolism; SAE, serious adverse event; ULN, upper limit of normal.