Tofacitinib Response in Ulcerative Colitis (TOUR): Early Response After Initiation of Tofacitinib Therapy in a Real-world Setting

Millie D Long, Anita Afzali, Monika Fischer, David Hudesman, Maisa Abdalla, Robert McCabe, Benjamin L Cohen, Ryan C Ungaro, Will Harlan, John Hanson, Gauree Konijeti, Steven Polyak, Timothy Ritter, Bruce Salzberg, Jennifer Seminerio, Emily English, Xian Zhang, Puza P Sharma, Hans H Herfarth, Millie D Long, Anita Afzali, Monika Fischer, David Hudesman, Maisa Abdalla, Robert McCabe, Benjamin L Cohen, Ryan C Ungaro, Will Harlan, John Hanson, Gauree Konijeti, Steven Polyak, Timothy Ritter, Bruce Salzberg, Jennifer Seminerio, Emily English, Xian Zhang, Puza P Sharma, Hans H Herfarth

Abstract

Background: Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Using a novel electronic reporting tool, we aimed to prospectively describe the onset of tofacitinib efficacy during induction therapy in a real-world study.

Methods: Patient-reported outcome data (PROs) including the simple clinical colitis activity index (SCCAI), PRO Measurement Identification Systems (PROMIS) measures, and adverse events were collected daily for the first 14 days and at day 28 and 56. Paired t tests and P for trend were utilized to compare changes in SCCAI over time. Bivariate analyses and logistic regression models were performed to describe response (SCCAI <5) and remission (SCCAI ≤2) by clinical factors.

Results: Of all included patients (n = 96), 67% had failed ≥2 biologics, and 61.5% were on concomitant steroids. Starting at day 3, PROs showed significant and persistent decline of the mean SCCAI (-1.1, P < 000.1) including significantly lower SCCAI subscores for stool frequency (-0.3; P < .003), bleeding (-0.3; P < .0002) and urgency (-0.2; P < .001). Steroid-free remission at day 14, 28, and 56 was achieved in 25%, 30.2%, and 29.2% of patients, respectively. Neither prior biologics nor endoscopic severity were independently predictive of response or remission in multivariate models. Numeric improvements in all PROMIS measures (anxiety, depression, social satisfaction) were seen through day 56. Rates of discontinuation due to adverse events were low.

Conclusions: In this prospective real-world study, tofacitinib resulted in a rapid and persistent improvement in UC disease activity PROs. The safety findings were consistent with the established safety profile of tofacitinib.

Keywords: patient report outcomes; safety; tofacitinib; ulcerative colitis.

Conflict of interest statement

M.L. has served as a consultant for AbbVie, UCB, Takeda, Janssen, Pfizer, Salix, Valeant, Lilly, Genentech, Roche, BMS, Target Pharmasolutions and has received research support from Pfizer and Takeda.

A.A. has served as a consultant for AbbVie, Takeda, Janssen, Bristol Myers Squibb, Pfizer, Eli Lilly, Gilead, DiaSorin, and TLL Pharmaceuticals; and as a speaker for AbbVie, Takeda, Janssen, Bristol Myers Squibb, and Pfizer.

M.F. has served as an advisory board member or consultant for AbbVie, Bristol Myer Squibb, Pfizer, Eli Lily, Takeda, Janssen, Scioto and as a DSMB member for Rebiotix.

D.H. has served as a consultant to Abbvie, BMS, Janssen, Pfizer, Takeda and has received research support from Janssen and Pfizer.

B.D. has served as an advisory board member or consultant for Abbvie, Celgene-Bristol Myers Squibb, Lilly, Pfizer, Sublimity Therapeutics, Takeda, TARGET RWE; CME Companies: Cornerstones, Vindico; Speaking: Abbvie; Educational Grant: Pfizer.

R.U. has served as an advisory board member or consultant for AbbVie, Janssen, Pfizer, and Takeda; research support from AbbVie, Boehringer Ingelheim, Eli Lily, and Pfizer; he is also funded by an National Institute of Health (NIH) K23 Career Development Award K23KD111995-01A1.

J,H, has served an advisory board member for Bristol Myers Squibb and for the Speakers Bureau of AbbVie and Pfizer.

G.K. has served as a consultant to Pfizer and ProciseDx and for the speakers bureau of Takeda.

S.P. has served as an advisory board member or consultant to Pfizer and Takeda; research support from Gilead, AbbVie, Seres, Bristol Myer Squibb, Pfizer, and Takeda.

T.R. has served on advisory boards for Abbive, Arena, Boeeringer Ingleheim, Bristol Myers, Ferring, Genentech, Gilead, Intercept, Iterative Scopes, Janssen, Lilly, Pfizer, Prometheus, and Takeda and as speaker for Abbvie, Bristol Myers, Janssen, Pfizer and Takeda.

J.S. has served as a consultant for AbbVie, UCB, Takeda, Janssen, Pfizer, BMS, Prometheus and has received research support from Takeda

P.S. is an employee of Pfizer Inc.

H.H.H. has served as a consultant to Alivio, BMS, Boehringer, ExeGi Pharma, Finch, Gilead, Janssen, Lycera, Merck, Otsuka, Pfizer, PureTech, and Seres; research support from Allakos, Artizan, and Pfizer.

All other authors have no conflicts to declare.

© 2022 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.

Figures

Figure 1.
Figure 1.
Decrease of SCCAI score in all patients (A) and in patients with a SCCAI ≥5 at baseline (B) during the initial 56 days of treatment with tofacitinib. The dashed line depicts a SCCAI = 5.
Figure 2.
Figure 2.
Response (SCCAI

Figure 3.

SCCAI subscores for stool frequency…

Figure 3.

SCCAI subscores for stool frequency (A), bleeding (B), and urgency (C) during the…

Figure 3.
SCCAI subscores for stool frequency (A), bleeding (B), and urgency (C) during the initial 56 days of treatment with tofacitinib. In each panel are shown the percentage of patients with improvement of ≥1 point compared to the baseline SCCAI subscores well as the percentage of patients with a subscore of ≤1 and 0.
Figure 3.
Figure 3.
SCCAI subscores for stool frequency (A), bleeding (B), and urgency (C) during the initial 56 days of treatment with tofacitinib. In each panel are shown the percentage of patients with improvement of ≥1 point compared to the baseline SCCAI subscores well as the percentage of patients with a subscore of ≤1 and 0.

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Source: PubMed

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