Dataset Information

Modified Mayo score versus Mayo score for evaluation of treatment efficacy in patients with ulcerative colitis: data from the tofacitinib OCTAVE program.

ABSTRACT:

Objectives

The subjectivity of the Physician Global Assessment (PGA) is a limitation of the Mayo score in assessing severity of ulcerative colitis (UC). We compared treatment efficacy using endpoint definitions based on modified Mayo (mMayo) score, versus those based on Mayo score, using data from the tofacitinib OCTAVE program.

Design

This post hoc analysis included data from two 8-week induction studies (OCTAVE Induction 1 and 2) and a 52-week maintenance study (OCTAVE Sustain).

Methods

Remission and clinical response [with nonresponder imputation (NRI)] were assessed using mMayo (without PGA) and Mayo scores, and further stratified by prior tumor necrosis factor inhibitor (TNFi) failure status.

Results

At week 8 of OCTAVE Induction 1 and 2, remission rates with placebo and tofacitinib 10 mg twice daily (BID), respectively, were 7.7% and 24.8% (mMayo) and 6.0% and 17.6% (Mayo). At week 52 of OCTAVE Sustain, remission rates with placebo, tofacitinib 5 and 10 mg BID, respectively, were 12.1%, 35.9%, and 42.1% (mMayo) and 11.1%, 34.3%, and 40.6% (Mayo). A statistically significant (p < 0.05) treatment effect of tofacitinib versus placebo was observed for remission and clinical response at all time points, regardless of scoring definition or prior TNFi failure status.

Conclusions

A significant effect of tofacitinib versus placebo was demonstrated across efficacy endpoints using mMayo score, consistent with previously reported data using Mayo score. Treatment effect sizes were generally similar regardless of scoring definition. This observation may help contextualize tofacitinib therapy outcomes with those of new UC therapies and support the use of Mayo score-based endpoints in UC clinical trials.

Trail registration

ClinicalTrials.gov identifiers: NCT01465763; NCT01458951; NCT01458574.

SUBMITTER: Sandborn WJ

PROVIDER: S-EPMC9726836 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Modified Mayo score <i>versus</i> Mayo score for evaluation of treatment efficacy in patients with ulcerative colitis: data from the tofacitinib OCTAVE program.

Sandborn William J WJ Sands Bruce E BE Vermeire Séverine S Leung Yvette Y Guo Xiang X Modesto Irene I Su Chinyu C Wang Wenjin W Panés Julian J

Therapeutic advances in gastroenterology 20221205

<h4>Objectives</h4>The subjectivity of the Physician Global Assessment (PGA) is a limitation of the Mayo score in assessing severity of ulcerative colitis (UC). We compared treatment efficacy using endpoint definitions based on modified Mayo (mMayo) score, <i>versus</i> those based on Mayo score, using data from the tofacitinib OCTAVE program.<h4>Design</h4>This post hoc analysis included data from two 8-week induction studies (OCTAVE Induction 1 and 2) and a 52-week maintenance study (OCTAVE Su ...[more]

PMID: 36506749

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Project description:Background and aimsTofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. Here, we evaluate the efficacy and safety of tofacitinib re-treatment following treatment interruption in patients with ulcerative colitis.MethodsHere, patients with clinical response to tofacitinib 10 mg b.d. induction therapy were randomised to receive placebo in OCTAVE Sustain. Those experiencing treatment failure after Week 8 of OCTAVE Sustain entered OCTAVE Open and re-initiated tofacitinib 10 mg b.d. [re-treatment subpopulation]; efficacy and safety data are presented up to Month 36 of OCTAVE Open.ResultsMedian time to treatment failure following interruption was 169 (95% confidence interval [CI], 94.0-179.0) and 123 [95% CI, 91.0-168.0] days for induction remitters, and induction responders but non-remitters, respectively. Following re-treatment with tofacitinib, rates (non-responder imputation after a patient discontinued; latest observation carried forward imputation after a patient advanced to a subsequent study [NRI-LOCF]) of clinical response, remission, and endoscopic improvement were 74.0%, 39.0%, and 55.0% at Month 2, and 48.5%, 37.4%, and 42.4% at Month 36, respectively. Among induction remitters and induction responders but non-remitters, clinical response rates at Month 36 were 60.6% and 42.4% [NRI-LOCF], respectively. Efficacy was recaptured regardless of prior tumour necrosis factor inhibitor failure status. The safety profile of tofacitinib 10 mg b.d. re-treatment was consistent with the overall cohort and demonstrated no new safety risks associated with exposure of ≤36 months.ConclusionsMedian time to treatment failure was numerically higher in induction remitters versus induction responders but non-remitters. Following treatment interruption, efficacy was safely and successfully recaptured with tofacitinib 10 mg b.d. re-treatment in a substantial proportion of patients [ClinicalTrials.gov:NCT01458574;NCT01470612].

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