Review for 10.1186/s12876-015-0239-9 (2015)

Reviewer's report
Title:Randomized Trial of Tofacitinib in Active Ulcerative Colitis: Analysis of
Efficacy Based on Patient-Reported Outcomes
Version:2Date:26 October 2014
Reviewer: Alessandro Armuzzi
Reviewer's report:
The manuscript “Randomized Trial of Tofacitinib in Active Ulcerative Colitis:
Analysis of Efficacy Based on Patient-Reported Outcomes” by Panés et al
reports about the effect of tofacitinib on ulcerative colitis patient’s reported
outcomes (PROs) by assessing and analyzing results from the 8-week,
multicenter, phase II randomized controlled trial (clinicaltrials.gov
NCT00787202).
The Inflammatory Bowel Disease Questionnaire (IBDQ) and the The
Inflammatory Bowel Disease Patient-Reported Treatment Impact (IBDPRTI,
version 2) were the used instruments to assess PROs (pre-defined secondary
efficacy measures in the original study protocol). By pooling all treatment groups,
posthoc analyses were performed to assess relationship between those PROs
instruments and the total and the partial Mayo score and the Mayo endoscopic
subscore.
Week 8 mean total IBDQ scores had improved vs baseline across all treatment
group, with significantly greater mean change for tofacitinib 15 mg BID group vs
PLB group. Statistically significant mean change vs baseline were reported also
across all 4 IBDQ domains, with the greatest improvement in the tofacitinib 15
mg BID group. Dose-related improvement were observed for all the 3 items of
the IBD PRTI, being the greatest improvement observed in the tofacitinib 15 mg
BID group. Finally, the correlation between the IBDQ and the Mayo based
outcomes (composite score, partial score, endoscopic subscore) showed general
discrete consistency (even if small-moderate at baseline and moderate-high at
week 8) and resulted approximately linear (and in the expected direction).
Similarly, also the correlation between the IBD PRTI and the Mayo based
outcomes (composite score, partial score, endoscopic subscore) were consistent
(moderately-to-highly consistent) and approximately linear. Interestingly, patients
achieving MH (defined as Mayo endoscopy score = 0) had IBDQ scores
significantly higher than patients without MH and they were significantly different
from patients without MH on all IBD PRTI components.
The study is very interesting and reports a detailed set of PROs on patients with
moderately-to-severely active UC who participated in the tofacitinib clinical phase
II trial.
Besides reinforcement of tofacitinib efficacy in the treatment of patients with
moderately-to-severely active ulcerative colitis, the main strength if this study is
the general support of the use of PROs for the assessment of drug efficacy as
complementary tool to clinical and endoscopic scores.
Main limitations of this study (small sample size from a single clinical trial, short
duration of the trial itself focusing only on patients with moderately-to-severely
active UC) have been recognized by authors in the discussion section.
The major criticism and suggestion is the lack analysis on the correlation
between the PROs and the stool frequency and rectal bleeding components of
the Mayo score (grouped or separated), that better reflect subjective report of
efficacy from the patients’ point of view.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I am participating in the Phase 3 trial on Tofacitinib in UC