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

Summary 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.

Persistence of treatment in patients with ulcerative colitis who responded to tofacitinib therapy: data from the open‐label, long‐term extension study, OCTAVE open

“…Full study design details for OCTAVE Induction 1 and 2, OCTAVE Sustain and OCTAVE Open have been reported previously. 6,7…”

“…Therefore, the duration of participation for an individual patient may range from approximately 4 years up to 7 years. Full study design details for OCTAVE Induction 1 and 2, OCTAVE Sustain and OCTAVE Open have been reported previously 6,7 …”

Chronic Intestinal Disorders in Humans and Pets: Current Management and the Potential of Nutraceutical Antioxidants as Alternatives

“…Tofacitinib (anti-JAK) is the latest drug available to treat IBD, in particular UC. Blocking the JAK-STAT pathway, it interferes with the signaling pathways of several cytokines [ 30 ].…”

Editorial: response to tofacitinib is associated with high rates of long‐term treatment persistence

“…A recent phase 3, multicentre, open-label, long-term extension study (OCTAVE Open) further validated the safety profile of tofacitinib which remained stable when patients were followed up to 7 years, and its efficacy was maintained up to 36 months. 4 Panaccione et al evaluated tofacitinib drug survival and persistence in the OCTAVE Open trial across selected subgroups of patients with differing levels of disease activity at baseline and explored the reasons for treatment discontinuation. 5 The authors observed high levels of tofacitinib treatment persistence across selected subpopulations of patients with a median time to discontinuation ranging from 4.0 to 5.6 years.…”

“…In these studies, tofacitinib was shown to have statistically significant efficacy in induction of remission and mucosal healing at 8 weeks, and in sustained remission and mucosal healing at 52 weeks, compared with placebo. A recent phase 3, multicentre, open‐label, long‐term extension study (OCTAVE Open) further validated the safety profile of tofacitinib which remained stable when patients were followed up to 7 years, and its efficacy was maintained up to 36 months 4 …”