Safety and efficacy of tofacitinib for treatment of ulcerative colitis: final analysis of OCTAVE Open, an open-label, long-term extension study with up to 7.0 years of treatment

Abstract

Background: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. We present final data from OCTAVE Open, an open-label, long-term extension study.

Aims: The primary objective of OCTAVE Open was to assess the safety and tolerability of long-term tofacitinib in patients with ulcerative colitis; evaluating efficacy was a secondary objective.

Methods: Eligible patients included OCTAVE Induction 1&2 non-responders and OCTAVE Sustain completers/treatment failures. Patients in remission at OCTAVE Open baseline received tofacitinib 5 mg b.d.; all others received 10 mg b.d. Incidence rates (unique patients with events/100 patient-years) for adverse events of special interest were calculated; ≤7.0 years of observation. Efficacy endpoints derived from Mayo score were reported ≤36 months (last scheduled endoscopy visit).

Results: In OCTAVE Open, 769 of 944 patients (81.5%) initially received tofacitinib 10 mg b.d. Among all patients (2440.8 patient-years of exposure), incidence rates (IRs; 95% confidence intervals) for deaths and adverse events of special interest were: deaths, 0.25 (0.09-0.54); serious infections, 1.61 (1.14-2.20); herpes zoster (non-serious and serious), 3.16 (2.47-3.97); opportunistic infections, 0.87 (0.54-1.33); major adverse cardiovascular events, 0.16 (0.04-0.42); malignancies (excluding non-melanoma skin cancer), 1.03 (0.67-1.52); non-melanoma skin cancer, 0.75 (0.45-1.19); deep vein thrombosis, 0.04 (0.00-0.23); pulmonary embolism, 0.21 (0.07-0.48). At Month 36, 66.9% and 40.3% showed clinical response, 64.6% and 37.1% had endoscopic improvement, and 58.9% and 33.7% maintained or achieved remission, with tofacitinib 5 and 10 mg b.d. respectively.

Conclusion: Tofacitinib demonstrated consistent safety up to 7.0 years. Data collected up to Month 36 support long-term efficacy beyond the 52-week maintenance study.

FIGURE 1

Overview of the tofacitinib phase 3 OCTAVE clinical programme. ^†Final complete efficacy assessment at Week 8/52. Treatment continued up to Week 9/53. ^‡Clinical response in OCTAVE Induction 1 and 2 was defined as a decrease from induction study baseline total Mayo score of ≥3 points and ≥30%, with a decrease in rectal bleeding subscore of ≥1 point or an absolute rectal bleeding subscore of 0 or 1. ^§Remission was defined as a total Mayo score of ≤2, with no individual subscore >1 and a rectal bleeding subscore of 0. Adapted from Winthrop et al (in accordance with the CC BY‐NC licence). b.d., twice daily; N, number of patients treated

FIGURE 2

Mean change from baseline of OCTAVE Open over time up to Month 60 in AST, ALT, LDL:HDL ratio, total cholesterol:HDL ratio, ANC, ALC and Hgb. Values are mean ± SE. ALC, absolute lymphocyte count; ALT, alanine aminotransferase; ANC, absolute neutrophil count; AST, aspartate aminotransferase; b.d., twice daily; BL, baseline; Hgb, haemoglobin; HDL, high‐density lipoprotein; LDL, low‐density lipoprotein; N, number of evaluable patients; SE, standard error

FIGURE 3

Proportions of patients in (A) the tofacitinib 5 mg b.d. group, and (B) the tofacitinib 10 mg b.d. group, who achieved clinical response, endoscopic improvement or remission, ‘as observed’ and with NRI‐LOCF, in OCTAVE Open (FAS). Data are per local read of endoscopy. Patients in remission at the start of OCTAVE Open were assigned to tofacitinib 5 mg b.d.; all other patients were assigned to tofacitinib 10 mg b.d. b.d., twice daily; FAS, full analysis set; N1, number of patients in the specified category with non‐missing data; n, number of patients with the specified response within the given category; NRI‐LOCF, non‐responder imputation was applied after a patient discontinued and last observation carried forward imputation after a patient advanced to a subsequent study up to the visit they would have reached if they had stayed in the study. Non‐responder imputation was applied for intermittent missing data

FIGURE 4

Proportion of patients in (A) the tofacitinib 5 mg b.d. group, and (B) the tofacitinib 10 mg b.d. group, who achieved PMS remission, ‘as observed’ and with NRI‐LOCF, in OCTAVE Open (FAS). Patients in remission at the start of OCTAVE Open were assigned to tofacitinib 5 mg b.d.; all other patients were assigned to tofacitinib 10 mg b.d. b.d., twice daily; FAS, full analysis set; N1, number of patients in the specified category with non‐missing data; n, number of patients with the specified response within the given category; NRI‐LOCF, non‐responder imputation was applied after a patient discontinued and last observation carried forward imputation after a patient advanced to a subsequent study up to the visit they would have reached if they had stayed in the study. Non‐responder imputation was applied for intermittent missing data; PMS, partial Mayo score