Dataset Information

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

ABSTRACT: Background and Aims:Tofacitinib 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. Methods:Patients ? 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. Results:In OCTAVE Induction 1 and 2, mean changes from baseline IBDQ were greater with tofacitinib 10 mg BID at Week 8 [28.9 and 31.5] versus placebo [15.4 and 17.2; 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 [-1.3] and 10 mg BID [0.6], and larger with placebo [-20.2; 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. Conclusions:Tofacitinib 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 numbers:NCT01465763, NCT01458951 and NCT01458574.

SUBMITTER: Panes J

PROVIDER: S-EPMC5881763 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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

Panés Julian J Vermeire Séverine S Lindsay James O JO Sands Bruce E BE Su Chinyu C Friedman Gary G Zhang Haiying H Yarlas Aaron A Bayliss Martha M Maher Stephen S Cappelleri Joseph C JC Bushmakin Andrew G AG Rubin David T DT

Journal of Crohn's & colitis 20180101 2

<h4>Background and aims</h4>Tofacitinib 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.<h4>Methods</h4>Patients ≥ 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] ...[more]

PMID: 29028981

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Project description:Background and aimsTo assess golimumab pharmacokinetics [PK] and exposure-response [ER] in adults with moderate-to-severe ulcerative colitis [UC] from the Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment [PURSUIT] studies.MethodsWe analysed golimumab PK and ER data of patients with moderate-to-severe UC from the PURSUIT-subcutaneous induction [N = 1064] and maintenance [N = 464] studies. Induction analyses evaluated serum golimumab concentration [SGC] and efficacy data through Week [wk] 6 following subcutaneous doses at wk0 and wk2; maintenance analyses assessed data through wk54 following 4-weekly dosing. ER relationships were assessed using trend, logistic regression, and receiver-operating-characteristic curve analyses.ResultsMedian SGCs peaked at induction wk2 for golimumab 100/50mg, 200/100mg, and 400/200mg. Wk6 median SGCs were 0.78, 1.78, and 4.01 ?g/ml, respectively. SGCs were sustained, reaching steady state approximately 8wks after golimumab maintenance commenced [wk14 of golimumab] regardless of induction dose. Median trough SGCs from maintenance wks8-44 ranged from 0.69 to 0.83 µg/ml [50 mg] and 1.33-1.58 µg/ml [100 mg]. SGCs were approximately dose proportional, and higher SGCs were associated with higher efficacy response rates during induction and maintenance. Factors associated with golimumab exposure were body weight, antibody-to-golimumab status, serum albumin, alkaline phosphatase, faecal markers, C-reactive protein, and pancolitis. SGCs of 2.5 µg/ml [induction wk6] and 1.4 µg/ml [maintenance steady-state trough] are potential target concentrations. Immunomodulators had no apparent impact on SGC with golimumab 100mg, whereas drug levels were slightly higher with golimumab 50mg with vs without immunomodulators.ConclusionsSGCs are approximately dose proportional, and a positive SGC-efficacy relationship exists during induction/maintenance golimumab treatment of adult UC patients. Optimal SGC targets require validation in prospective studies.

Dataset Information

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

Publications

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

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