TABLE 4.
Summary of liver function test values as multiples of the upper limit of normal and laboratory data meeting criteria for discontinuation in OCTAVE Open
| n (%) | Tofacitinib 5 mg b.d. (N = 175) | Tofacitinib 10 mg b.d. (N = 769) | Tofacitinib All (N = 944) |
|---|---|---|---|
| ALT | |||
| ≥1 ×ULN | 86 (49.1) | 211 (27.4) | 297 (31.5) |
| ≥2 ×ULN | 25 (14.3) | 52 (6.8) | 77 (8.2) |
| ≥3 ×ULN | 14 (8.0) | 19 (2.5) | 33 (3.5) |
| AST | |||
| ≥1 ×ULN | 72 (41.1) | 180 (23.4) | 252 (26.7) |
| ≥2 ×ULN | 22 (12.6) | 35 (4.6) | 57 (6.0) |
| ≥3 ×ULN | 10 (5.7) | 13 (1.7) | 23 (2.4) |
| Laboratory data for discontinuations | |||
| Two sequential Hgb <8.0 g/dL or >30% decrease from baseline | 0 (0.0) | 11 (1.4) | 11 (1.2) |
| Two sequential ANC <750 neutrophils/mm3 | 0 (0.0) | 1 (0.1) | 1 (0.1) |
| Two sequential ALC <500 lymphocytes/mm3 | 1 (0.6) | 14 (1.8) | 15 (1.6) |
| Two sequential creatine phosphokinase elevations >10 ×ULN a | 2 (1.1) | 4 (0.5) | 6 (0.6) |
| Two sequential AST or ALT elevations | |||
| ≥3 ×ULN with at least one total bilirubin value ≥2 ×ULN b | 1 (0.6) | 0 (0.0) | 1 (0.1) |
| Two sequential AST or ALT elevations | |||
| ≥5 ×ULN | 1 (0.6) | 1 (0.1) | 2 (0.2) |
Reference ranges for ULN parameters were dependent on patient sex and age.
Abbreviations: ALC, absolute lymphocyte count; ALT, alanine aminotransferase; ANC, absolute neutrophil count; AST, aspartate aminotransferase; b.d., twice daily; Hgb, haemoglobin; N, number of patients in the treatment group; n, number of patients meeting criteria; ULN, upper limit of normal.
Discontinuation was required unless the causality was known not to be medically serious (e.g. exercise induced).
Two sequential AST or ALT elevations ≥3 ×ULN alone was not a reason for discontinuation. Discontinuation was only required if accompanied by at least one total bilirubin value ≥2 ×ULN, or signs or symptoms consistent with hepatic injury.