Persistence of Treatment in Patients With Ulcerative Colitis who Responded to Tofacitinib Therapy

Data From the Open-label, Long-term Extension Study, OCTAVE Open

Remo Panaccione; Maria T. Abreu; Irina Lazariciu; Rajiv Mundayat; Nervin Lawendy; Leonardo Salese; John C. Woolcott; Bruce E. Sands; María Chaparro

Disclosures

Aliment Pharmacol Ther. 2022;55(12):1534-1544. 

In This Article

Abstract and Introduction

Abstract

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC).

Aim: This post hoc analysis evaluated tofacitinib persistence in patients with UC in OCTAVE Open, an open-label, long-term extension study of patients receiving tofacitinib 5 or 10 mg twice daily.

Methods: Kaplan-Meier estimates for tofacitinib drug survival and reasons for discontinuations were evaluated. Baseline factors were analysed as predictors of persistence.

Results: This analysis included 603 patients: 280 entered OCTAVE Open with a clinical response (164 in remission and 116 not in remission), 220 were delayed responders, 75 were retreatment responders and 35 were dose escalation responders, treated for up to 7 years in OCTAVE Open. Of these, 118 (42.1%) responders, 121 (55.0%) delayed responders, 40 (53.3%) retreatment responders and 17 (48.6%) dose escalation responders discontinued tofacitinib with a median time to discontinuation of 5.6, 4.5, 4.0 and 4.4 years, respectively. The estimated 2- and 5-year drug survival rates in the responders (including patients in remission and not in remission) were 73.9% and 54.5%, respectively. Corresponding persistence values for delayed responders were 69.5% and 45.2%, for retreatment responders, 70.7% and 40.0%, and for dose escalation responders, 74.3% and 32.8%.

Conclusion: In OCTAVE Open, a high proportion of patients maintained tofacitinib treatment, with the median survival by group ranging from 4.0 to 5.6 years although these analyses are post hoc and limited by sample size. Further research should focus on factors to enhance persistence with tofacitinib treatment in patients with UC.

Introduction

Ulcerative colitis (UC) is a chronic, immune-mediated, idiopathic inflammatory bowel disease which is characterised by mucosal inflammation in the rectum and colon.[1,2] The primary goal of management of patients with moderate to severe UC is to achieve sustained steroid-free remission, improve quality of life, reduce morbidity and prevent disease complications and surgery.[2–4]

Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of UC. The efficacy and safety of tofacitinib were demonstrated in a phase 2, double-blind, placebo-controlled, 8-week induction study (NCT00787202),[5] two identical phase 3, randomised, placebo-controlled, 8-week induction studies (OCTAVE Induction 1 and 2; NCT01465763 and NCT01458951) and a phase 3, randomised, placebo-controlled, 52-week maintenance study (OCTAVE Sustain; NCT01458574).[6] The long-term safety and efficacy of tofacitinib in patients with UC have been evaluated up to 7 years in a phase 3, multicentre, open-label, long-term extension study (OCTAVE Open; NCT01470612).[7] In OCTAVE Open, the safety profile of tofacitinib remained stable and efficacy was maintained with tofacitinib 5 and 10 mg b.d. up to 36 months.[7]

Time on treatment, also referred to as survival time, time to discontinuation, persistence or durability of treatment, is a surrogate measure of treatment success (effectiveness, tolerability and safety) in the long-term management of disease[8,9] and also represents a persistent response to a specific mode of action.

The objective of this post hoc analysis was to evaluate tofacitinib drug survival and persistence in OCTAVE Open, up to 7 years, across selected subgroups of patients with differing levels of disease activity at baseline OCTAVE Open and explore the reasons for treatment discontinuation, and to evaluate baseline clinical and demographic factors that may influence treatment persistence.

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