Tofacitinib in Patients with Ulcerative Colitis: Health-Related Quality of Life in Phase 3 Randomised Controlled Induction and Maintenance Studies

Abstract

Background and AimsTofacitinib is an oral, small molecule Janus kinase [JAK] inhibitor that is being investigated for ulcerative colitis [UC]. We evaluated health-related quality of life [HRQoL] in tofacitinib UC Phase 3 studies.MethodsPatients ≥ 18 years old in OCTAVE Induction 1 [N = 598] and 2 [N = 541] with moderately to severely active UC were randomised [1:4] to placebo or tofacitinib 10 mg twice daily [BID] for 8 weeks. Subsequently, OCTAVE Sustain re-randomised [1:1:1] clinical responders [N = 593] from induction studies to placebo, tofacitinib 5 mg BID, or 10 mg BID, for 52 weeks. Inflammatory Bowel Disease Questionnaire [IBDQ] and SF-36v2® Health Survey [SF-36v2] assessed HRQoL.ResultsIn OCTAVE Induction 1 and 2, mean changes from baseline IBDQ were greater with tofacitinib 10 mg BID at Week 8 [40.7 and 44.6] versus placebo [21.0 and 25.0; p < 0.0001]; mean changes from baseline SF-36v2 Physical and Mental Component Summaries [PCS/MCS] were also greater with 10 mg BID [PCS: 6.8 and 6.8; MCS: 6.8 and 7.6] versus placebo [PCS: 2.5 and 4.6; MCS: 3.5 and 4.4; p < 0.01]. In OCTAVE Sustain atWeek 52, changes in IBDQ were maintained with tofacitinib 5 mg [3.7] and 10 mg BID [4.8], and larger with placebo [-26.5; p < 0.0001]. Changes in SF-36v2 PCS/MCS were also maintained with 5 mg [PCS: 0.0; MCS: -1.0] and 10 mg BID [PCS: 0.3; MCS: 0.1] versus placebo [PCS: -5.2; MCS: -6.7; p < 0.0001] at Week 52 in OCTAVE Sustain.ConclusionsTofacitinib 10 mg BID induction therapy significantly improved HRQoL versus placebo at Week 8. Improvements were maintained through 52 weeks’ maintenance therapy with tofacitinib 5 mg and 10 mg BID.ClinicalTrials.gov registration numbersNCT01465763, NCT01458951 and NCT01458574

Fatigue in Inflammatory Bowel Diseases: Etiologies and Management

“…IBD therapy and control of inflammation is consistently associated with improvement in fatigue. In post hoc analyses of various randomized trials, treatment of CD with infliximab, adalimumab, certolizumab, or ustekimumab over placebo is associated with improvement in fatigue, as measured by the IBDQ, SF-36, EQ-5D, and FACIT [41][42][43][44] and similarly in patients with UC, upon treatment with infliximab, adalimumab, golimumab, vedolizumab, or tofacitinib [45][46][47][48][49]. Improvement in fatigue has also been seen in patients with UC who were treated with non-biologic therapies, such as immunomodulators and 5-aminosalicylates (ASA) [50].…”

Therapies in Inflammatory Bowel Disease Patients with Extraintestinal Manifestations

“…Inflammatory back pain criteria sets and mnemonic for assessment of axial spondyloarthritis, according to ASAS. Adapted from [196] In patients with back pain ≥3 months and age at onset back pain <45 years (with/without peripheral manifestations) ( Pan-JAK inhibitor Pilot, phase IIb study [136,137] ✓ Real life data ✓ OLE study [138] ✓ Objective inflammation [139] Approved 2018 (Xeljanz ® ) [140,141] Approved 2012 [142] as efficient as adalimumab [142] ✓Phase IIb study [45] Anti-IL-6 receptor ✓ Pilot study [164] 1 case report of exacerbation [165] 1 case of improvement [166] ✓ Approved 2010 (Actemra ® ) [167] Higher risk of intestinal perforation [168] Phase II-III [169] No studies Anti-IL-17 RA Worsen, phase IIa [189] No studies No studies (phase II canceled) ✓ Phase III [190] ✓ Approved 2017 (Siliq ® , Kyntheum ® ) [191] Secukinumab AIN457, KB03303A…”

Вплив Біологічної Терапії У Хворих З Неспецифічним Виразковим Колітом При Супутньому Ураженні Суглобів

“…Препаратами вибору є препарати 5-аміносаліцилової кислоти (месалазин, мезакол, салофальк, тощо), які впливають як на кишкову, так і на суглобову симптоматику. У разі вираженої рефрактерності до даних препаратів додатково призначають курси терапії глюкокортикоїдами [6].…”