Summary of safety and laboratory data
| Weeks 0–6 tofacitinib 10 mg bid (N=111) | Weeks 6–12 tofacitinib 10 mg bid | ||
|---|---|---|---|
| + Atorvastatin (N=50) | + Placebo (N=47) | ||
| Patients with AE, n (%) | 52 (46.8) | 21 (42.0) | 19 (40.4) |
| Serious AE, n (%)* | 2 (1.8) | 0 | 1 (2.1) |
| Severe AE, n (%)† | 4 (3.6) | 0 | 1 (2.1) |
| Serious infections, n (%)‡ | 1 (0.9) | 0 | 1 (2.1) |
| Discontinuation due to AE, n (%) | 7 (6.3) | 3 (6.0) | 2 (4.3) |
| AE by system organ class (all causalities) affecting ≥5% of patients in any treatment group, n (%) | |||
| Gastrointestinal disorders | 12 (10.8) | 4 (8.0) | 3 (6.4) |
| General disorders and administration site conditions | 3 (2.7) | 4 (8.0) | 2 (4.3) |
| Infections and infestations | 16 (14.4) | 4 (8.0) | 7 (14.9) |
| Investigations§ | 5 (4.5) | 6 (12.0) | 3 (6.4) |
| Musculoskeletal and connective tissue disorders | 7 (6.3) | 3 (6.0) | 3 (6.4) |
| Nervous system disorders | 8 (7.2) | 1 (2.0) | 1 (2.1) |
| Respiratory, thoracic and mediastinal disorders¶ | 4 (3.6) | 4 (8.0) | 1 (2.1) |
| Tofacitinib 10 mg bid | |||
| Laboratory values at weeks 0 (enrolment), 6 (baseline) and 12 | + Atorvastatin (N=50) | + Placebo (N=47) | |
| Haemoglobin, g/dl, mean (SD) | |||
| Week 0 | 12.4 (1.5) | 12.4 (1.6) | |
| Week 6 | 12.6 (1.4) | 12.6 (1.5) | |
| Week 12 | 12.5 (1.3) | 12.7 (1.3) | |
| Neutrophil count, 103/mm3, mean (SD) | |||
| Week 0 | 5.7 (1.8) | 5.3 (2.2) | |
| Week 6 | 4.4 (1.9) | 4.1 (1.8) | |
| Week 12 | 4.7 (2.0) | 4.0 (1.7) | |
| Serum creatinine, µmol/l, mean (SD) | |||
| Week 0 | 53.38 (15.25) | 53.38 (15.25) | |
| Week 6 | 61.00 (30.50) | 61.00 (15.25) | |
| Week 12 | 61.00 (15.25) | 61.00 (15.25) | |
| Incidence to week 12 | |||
| Decreased haemoglobin, n (%) | |||
| −1 to −2 g/dl | 3 (6.0) | 3 (6.4) | |
| −1.99 to −2.99 g/dl; or haemoglobin 7–8 g/dl | 0 | 0 | |
| ≥−3 g/dl; or haemoglobin ≤7 g/dl | 0 | 0 | |
| Neutropenia, n (%) | |||
| 1500–1999 cells/mm3 | 5 (10.0) | 4 (8.5) | |
| 500–1499 cells/mm3 | 0 | 3 (6.4) | |
| <500 cells/mm3 | 0 | 0 | |
| Alanine aminotransferase elevations >2× ULN, n (%) | 0 | 1 (2.1) | |
| Aspartate aminotransferase elevations >2× ULN, n (%) | 0 | 0 | |
| Creatine phosphokinase elevations >2× ULN, n (%)** | 5 (10.0) | 3 (6.4) | |
| Total bilirubin elevations >1.5× ULN, n (%) | 0 | 0 | |
| Creatinine elevations from average of screening and baseline values of 33%, n (%)** | 0 | 0 | |
| Creatinine elevations from average of screening and baseline values of 50%, n (%)** | 0 | 0 | |
| Reduction in lymphocytes (<1000/µl), n (%)** | 0 | 1 (2.1) | |
| Reduction in lymphocytes (<500/µl), n (%)** | 0 | 0 | |
| Hypertension at week 12 (Joint National Committee 7 criteria); n (%) | |||
| Week 0 | 10/50 (20.0) | 8/47 (17.0) | |
| Week 6 | 6/50 (12.0) | 11/47 (23.4) | |
| Week 12 | 8/46 (17.4) | 13/46 (28.3) | |
*Any untoward medical occurrence at any dose that resulted in death, was life threatening, required inpatient hospitalisation or prolongation of existing hospitalisation, resulted in persistent or significant disability/incapacity; and/or resulted in congenital anomaly/birth defect.
†Indicates severity of AE.
‡Any infection (viral, bacterial and fungal) requiring hospitalisation or parenteral antimicrobial agents.
§At 6–12 weeks, included blood cholesterol increase (two patients in placebo/tofacitinib group), blood creatine phosphokinase increase, blood potassium decrease, blood triglycerides increase, abnormal electrocardiogram, weight increase (one patient each in atorvastatin/tofacitinib group) and hepatic enzyme increase (one patient in each group).
¶At 6–12 weeks, included cough and sinus congestion (one patient each in atorvastatin/tofacitinib group), oropharyngeal pain (two patients in atorvastatin group) and emphysema (one patient in placebo/tofacitinib group).
**Confirmed elevations (occurring at two consecutive visits).
AE, adverse event; bid, twice daily; ULN, upper limit of normal.