Abstract and Introduction
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.
Ulcerative colitis is a chronic, immune-mediated, idiopathic inflammatory bowel disease that is characterised by mucosal inflammation in the rectum and colon.[1,2] The management of patients with moderate to severe ulcerative colitis often requires long-term maintenance treatment, the aims of which are to achieve sustained steroid-free remission, improve quality of life, reduce morbidity and prevent colorectal cancer.[2–4]
Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. The efficacy and safety of tofacitinib were demonstrated in a phase 2, double-blind, placebo-controlled, 8-week induction study (NCT00787202), two identical phase 3, randomised, double-blind, placebo-controlled, 8-week induction studies (OCTAVE Induction 1 and 2; NCT01465763 and NCT01458951) and one phase 3, randomised, double-blind, placebo-controlled, 52-week maintenance study (OCTAVE Sustain; NCT01458574).
The safety and efficacy of tofacitinib in patients with ulcerative colitis have been further evaluated in a phase 3, multicentre, open-label, long-term extension study (OCTAVE Open; ClinicalTrials.gov: NCT01470612). Patients enrolled in OCTAVE Open received tofacitinib for up to 7.0 years. The primary objective of OCTAVE Open was to assess the safety and tolerability of long-term tofacitinib therapy in patients with ulcerative colitis. A secondary objective was to evaluate the efficacy of long-term tofacitinib therapy in patients with ulcerative colitis. Here, we report the final safety and efficacy data from OCTAVE Open.
Aliment Pharmacol Ther. 2022;55(4):464-478. © 2022 Blackwell Publishing