Long-Term Improvement in the Patient-Reported Outcomes of Rectal Bleeding, Stool Frequency, and Health-Related Quality of Life with Tofacitinib in the Ulcerative Colitis OCTAVE Clinical Program

Abstract

Background: Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). The tofacitinib OCTAVE clinical program included phase III induction (OCTAVE Induction 1 and 2) and maintenance (OCTAVE Sustain) studies, and an open-label, long-term extension study (OCTAVE Open).

Objective: This post hoc analysis assessed selected long-term, disease-specific patient-reported outcome (PRO) and health-related quality-of-life (HRQoL) measurements in patients with UC receiving tofacitinib in the OCTAVE clinical program.

Methods: Analyses included patients from OCTAVE Open assigned to tofacitinib 5 mg twice daily (subpopulation in remission at Week 52 of OCTAVE Sustain). OCTAVE Open data from the final analyses are shown to Month 48. Endpoints included rectal bleeding subscore (RBS) = 0, stool frequency subscore (SFS) ≤ 1, and HRQoL measure, Inflammatory Bowel Disease Questionnaire (IBDQ) remission (IBDQ total score ≥ 170); with non-responder imputation for missing data at all visits, and last observation carried forward for visits after a patient advanced to the next study (NRI-LOCF). Observed cases were also assessed.

Results: At Month 48, of 175 patients, 95 (54.3%) and 96 (54.9%) achieved/maintained RBS = 0 and SFS ≤ 1, respectively (NRI-LOCF). Additionally, 93 (53.1%) patients achieved/maintained IBDQ remission at Month 48 (NRI-LOCF).

Conclusions: Among patients who entered OCTAVE Open in remission, most maintained normalization of rectal bleeding and improvement in stool frequency for ≤ 4 years of follow-up in OCTAVE Open. IBDQ remission was also generally maintained in OCTAVE Open. These data show robust maintenance of key UC PROs and durability of response with tofacitinib 5 mg twice daily.

Trial registration: http://www.

Clinicaltrials: gov (NCT01465763 [21/10/2011]; NCT01458951 [21/10/2011]; NCT01458574 [21/10/2011]; NCT01470612 [21/10/2011]).

Conflict of interest statement

David P. Hudesman has received research support from Janssen and Pfizer Inc; consulting fees from UCB; and personal fees from AbbVie, Bristol-Myers Squibb, Janssen, Pfizer Inc, Samsung, and Takeda. Joana Torres has received advisory board fees from Arena, Galapagos, Janssen, and Pfizer Inc; research support from AbbVie and Janssen; and lecture fees from Galapagos and Janssen. Leonardo Salese, John C. Woolcott, Rajiv Mundayat, and Chinyu Su are employees and stockholders of Pfizer Inc. Mahmoud H. Mosli has received research support from Takeda; and lecture fees from AbbVie, Hikma, Janssen, Pfizer Inc, and Takeda. Jessica R. Allegretti has received consulting fees from Artugen, Bacainn, Bristol-Myers Squibb, Celgene, Finch Therapeutics, Iterative Scopes, Janssen, Morphic, Pandion, and Pfizer Inc; and research support from Merck.

© 2022. The Author(s).

Figures

Fig. 1

Proportions of tofacitinib 5 mg twice daily-treated patients in remission at baseline with RBS = 0a in OCTAVE Open (FAS, NRI-LOCF, and observed). NRI was used for missing data at all visits and LOCF was used for visits after a patient advanced to the next study. aThe RBS ranges from 0 to 3; an RBS of 0 equates to no blood seen, and the daily bleeding score represents the most severe bleeding of the day. BL baseline, FAS full analysis set, N number of patients treated in each treatment group, n number of patients with the specified response within the given category, NRI-LOCF non-responder imputation, last observation carried forward, RBS rectal bleeding subscore

Fig. 2

Proportions of tofacitinib 5 mg twice daily-treated patients in remission at baseline with SFS ≤ 1a in OCTAVE Open (FAS, NRI-LOCF, and observed). NRI was used for missing data at all visits and LOCF was used for visits after a patient advanced to the next study. aThe SFS ranges from 0 to 3; an SFS of 0 equates to a normal number of stools for the patient, and an SFS of 1 equates to one to two stools more than normal. Each patient serves as his or her own control to establish the degree of abnormality of the stool frequency. Normal number of bowel movements represents the number of bowel movements when not having a flare. BL baseline, FAS full analysis set, N number of patients treated in each treatment group, n number of patients with the specified response within the given category, NRI-LOCF non-responder imputation, last observation carried forward, SFS stool frequency subscore

Fig. 3

Proportions of tofacitinib 5 mg twice daily-treated patients in remission at baseline with IBDQ remissiona in OCTAVE Open (FAS, NRI-LOCF, and observed). NRI was used for missing data at all visits and LOCF was used for visits after a patient advanced to the next study. a IBDQ remission was defined as an IBDQ total score of ≥ 170. BL baseline, FAS full analysis set, IBDQ Inflammatory Bowel Disease Questionnaire, N number of patients treated in each treatment group, n number of patients with the specified response within the given category, NRI-LOCF non-responder imputation, last observation carried forward