C0364 - Assessment of Health-Related Quality of Life and Patient-Reported Outcomes With Tofacitinib Treatment Stratified by Age in Patients From the OCTAVE Ulcerative Colitis Clinical Program

Monday, October 24, 2022

3:00 PM – 5:00 PM ET

Location: Crown Ballroom

Presenting Author(s)

Marla C. Dubinsky, MD

Susan and Leonard Feinstein IBD Center, Icahn School of Medicine, Mount Sinai
New York, New York

Marla C. Dubinsky, MD¹, Luc Biedermann, MD², Ailsa Hart, MD³, Julian Panés, MD, PhD⁴, David T. Rubin, MD, FACG⁵, Marc Fellmann, PhD⁶, Sean Gardiner, MD⁷, Jerome Paulissen, MS⁷, Majid A. Almadi, MD⁸
¹Susan and Leonard Feinstein IBD Center, Icahn School of Medicine, Mount Sinai, New York, NY; ²University Hospital Zürich, Zürich, Zurich, Switzerland; ³IBD Unit, St Mark’s Hospital, London, England, United Kingdom; ⁴Formerly, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Catalonia, Spain; ⁵University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, IL; ⁶Pfizer Switzerland AG, Zürich, Zurich, Switzerland; ⁷Pfizer Inc, New York, NY; ⁸College of Medicine, King Saud University, Riyadh, Ar Riyad, Saudi Arabia

Introduction: Tofacitinib is an oral small molecule JAK inhibitor for the treatment of UC. Consistent with previous studies in patients (pts) with inflammatory bowel disease (IBD) and the general population, analyses from the tofacitinib OCTAVE UC clinical program demonstrated that older age was associated with poorer health outcomes in pts with UC.¹ To further understand the relationship between age and risk/benefit of tofacitinib, this post hoc analysis assessed HRQoL and pt-reported outcomes (PROs) stratified by age among pts enrolled in the tofacitinib OCTAVE UC clinical program.

Methods: Data up to Week (W)8 of the Phase (P)3 induction studies (OCTAVE Induction 1&2 [NCT01465763; NCT01458951]), W52 of the P3 maintenance study (OCTAVE Sustain [NCT01458574]), and Month 48 of the open-label, long term extension (OLE) study (OCTAVE Open [NCT01470612]) were analyzed. Proportions of pts with an IBD Questionnaire (IBDQ) total score ≥ 170 (i.e., IBDQ remission; cut-off generally corresponds to clinical remission), and mean changes from induction study baseline in the Mayo stool frequency subscore (SFS) and rectal bleeding subscore (RBS), stratified by age, were evaluated.

Results: The age distribution of pts who enrolled in the OCTAVE UC clinical program was generally similar across the studies and treatment groups.¹In OCTAVE Induction 1&2 and OCTAVE Sustain, proportions of pts who received tofacitinib treatment and who had an IBDQ total score ≥ 170 were generally higher than those who received placebo (PBO), regardless of age (Figure a–b). In OCTAVE Open, proportions of pts treated with tofacitinib 5 mg BID and with an IBDQ total score ≥ 170 were generally similar among the age groups (Figure c). A trend toward better HRQoL with older age was observed in the tofacitinib 10 mg BID group (Figure d). In OCTAVE Induction 1&2, pts who received tofacitinib 10 mg BID had a greater change from baseline in SFS and RBS compared with PBO, regardless of age. In OCTAVE Sustain and OCTAVE Open, there was no consistent trend for change from baseline in SFS among age and treatment groups, and similar changes from baseline in RBS were observed across age groups among tofacitinib-treated pts (Table).

Discussion: Tofacitinib demonstrated consistent efficacy for achieving IBDQ remission and was associated with improvements in PROs across all age groups. This analysis was limited by the small number of pts in each age group.

Reference

1. Lichtenstein GR et al. Inflamm Bowel Dis. 2022; in press

Figure: Figure. Proportions of patients with an Inflammatory Bowel Disease Questionnaire total score ≥ 170 among patients at a) Week 8 of OCTAVE Induction 1&2[a] and b) Week 52 of OCTAVE Sustain[a] and in the c) tofacitinib 5 mg BID[b] and d) tofacitinib 10 mg BID[b] groups in OCTAVE Open, stratified by age.

Values above brackets show the treatment difference from placebo (95% CI)
[a] Non-responder imputation for missing data
[b] Non-responder imputation for missing data at all visits but last observation carried forward for visits after a patient advanced to next study

BID, twice daily; CI, confidence interval; IBDQ, Inflammatory Bowel Disease Questionnaire; n, number of patients with the specified response within the given category; N, number of patients in the analysis set; N1; number of patients who, based on their enrollment dates and last non-missing IBDQ total score, could have reached the specified timepoint by the end of the study; OLE, open-label, long-term extension

Table. Change from induction study baseline in Mayo stool frequency and rectal bleeding subscores among patients in the OCTAVE UC clinical program, stratified by age (full analysis set, observed)
		OCTAVE Induction 1&2^a			OCTAVE Sustain^b		OCTAVE Open^c
		Placebo (N=234)	Tofacitinib 10 mg BID (N=905)	Placebo (N=198)	Tofacitinib 5 mg BID (N=198)	Tofacitinib 10 mg BID (N=197)	Tofacitinib 5 mg BID (N=175)	Tofacitinib 10 mg BID (N=769)
Change from baseline in Mayo stool frequency subscore, mean (SD)
Age category (years)	18 to < 30	–0.5 (0.8)	–0.9 (1.1)	–2.2 (1.0)	–1.8 (1.0)	–2.2 (0.7)	–2.0 (1.0)	–1.9 (1.0)
	30 to < 40	–0.5 (0.8)	–1.0 (1.0)	–1.4 (1.2)	–1.4 (1.0)	–1.6 (0.8)	–1.9 (1.2)	–2.2 (0.9)
	40 to < 50	–0.7 (0.9)	–1.1 (1.1)	–1.6 (0.7)	–1.7 (0.9)	–1.6 (1.0)	–1.9 (0.9)	–2.4 (0.6)
	50 to < 60	–0.6 (1.0)	–1.3 (1.0)	–1.8 (0.9)	–1.9 (1.0)	–1.9 (0.7)	–2.0 (1.2)	–2.0 (0.8)
	≥ 60	–0.6 (0.8)	–1.1 (1.0)	–0.7 (1.1)	–2.1 (1.0)	–1.5 (1.0)	–1.8 (0.8)	–2.3 (0.7)
Change from baseline in Mayo rectal bleeding subscore, mean (SD)
Age category (years)	18 to < 30	–0.8 (0.8)	–1.0 (0.9)	–1.7 (0.5)	–1.5 (0.8)	–1.7 (0.6)	–1.6 (0.5)	–1.6 (0.7)
	30 to < 40	–0.6 (0.8)	–1.1 (0.9)	–1.4 (0.7)	–1.3 (0.7)	–1.5 (0.7)	–1.5 (0.9)	–1.7 (0.7)
	40 to < 50	–0.7 (0.8)	–1.1 (0.9)	–1.6 (0.9)	–1.4 (0.8)	–1.5 (0.7)	–1.6 (0.7)	–1.7 (0.6)
	50 to < 60	–0.7 (0.8)	–1.2 (0.8)	–1.4 (0.5)	–1.6 (0.6)	–1.5 (0.5)	–1.6 (0.6)	–1.5 (0.6)
	≥ 60	–0.8 (1.0)	–1.2 (0.8)	–0.7 (1.1)	–1.6 (0.6)	–1.4 (0.7)	–1.6 (0.6)	–1.6 (0.5)
^aData are taken from Week 8 of OCTAVE Induction 1&2 ^bData are taken from Week 52 of OCTAVE Sustain ^cData are taken from Month 48 of OCTAVE Open BID, twice daily; N, number of patients; OLE, open-label, long-term extension; SD, standard deviation; UC, ulcerative colitis

Disclosures:

Marla Dubinsky: AbbVie – Consultant. Arena Pharmaceuticals – Consultant. Bristol Myers Squibb – Consultant. Celgene – Consultant. Eli Lilly – Consultant. Galapagos – Consultant. Genetech – Consultant. Gilead Sciences – Consultant. Janssen Pharmaceuticals – Consultant. Pfizer Inc – Consultant. Prometheus Laboratories – Consultant. Takeda – Consultant. Trellus Health – Shareholder. UCB – Consultant.

Luc Biedermann: Abbvie – Consultant. Calypso – Consultant. Esocap – Consultant. Ewopharma – Consultant. Falk – Consultant. Ferring – Consultant. Janssen – Consultant. MSD – Consultant. Pfizer Inc – Consultant. Sanofi – Consultant. Shire – Consultant. Takeda – Consultant. Vifor – Consultant.

Ailsa Hart: AbbVie – Advisory Committee/Board Member, Consultant, Lecture fees. Allergan – Consultant. Atlantic – Advisory Committee/Board Member, Consultant, Lecture fees. Bristol-Myers Squibb – Advisory Committee/Board Member, Consultant, Lecture fees. Celltrion – Advisory Committee/Board Member, Consultant, Lecture fees. Falk – Advisory Committee/Board Member, Consultant, Lecture fees. Ferring – Advisory Committee/Board Member, Consultant, Lecture fees. Genentech – Global Steering Committee. Janssen – Advisory Committee/Board Member, Consultant, Lecture fees. MSD – Advisory Committee/Board Member, Consultant, Lecture fees. Napp – Advisory Committee/Board Member, Consultant, Lecture fees. Pfizer Inc – Advisory Committee/Board Member, Consultant, Lecture fees. Pharmacosmos – Advisory Committee/Board Member, Consultant, Lecture fees. Shire – Advisory Committee/Board Member, Consultant, Lecture fees. Takeda – Advisory Committee/Board Member, Consultant, Lecture fees.

Julian Panés: AbbVie – Grant/Research Support, Personal fees. Arena – Personal fees. Athos – Personal fees. Boehringer Ingelheim – Personal fees. Celgene – Personal fees. Celltrion – Personal fees. Ferring Pharmaceuticals – Personal fees. Galapagos – Personal fees. Genentech/Roche – Personal fees. GSK – Personal fees. Immunic – Personal fees. Janssen Pharmaceuticals – Personal fees. Mirum – Personal fees. Morphic – Personal fees. Nestlé – Personal fees. Origo – Personal fees. Pandion – Personal fees. Pfizer Inc – Grant/Research Support, Personal fees. Progenity – Personal fees. Takeda – Personal fees. Theravance Biopharma – Personal fees. Wassermann – Personal fees.

David Rubin: AbbVie – Consultant. Alimentiv Inc. – Consultant. AltruBio – Consultant. Arena Pharmaceuticals – Consultant. Aslan Pharmaceuticals – Consultant. Athos Therapeutics – Consultant. Bellatrix Pharmaceuticals – Consultant. Boehringer Ingelheim, Ltd. – Consultant. Bristol Myers Squibb – Consultant. Celgene Corp/Syneos – Consultant. ClostraBio – Consultant. Connect BioPharma – Consultant. EcoR1 – Consultant. Genentech/Roche – Consultant. Gilead Sciences – Consultant. Ironwood Pharmaceuticals – Consultant. Iterative Scopes – Consultant. Janssen – Consultant. Kaleido Biosciences – Consultant. Lilly, Eli & Co – Consultant. Materia Prima – Consultant. Pfizer – Consultant. Prometheus Biosciences – Consultant. Reistone Biopharma – Consultant. Seres Therapeutics, Inc – Consultant. Takeda – Consultant, Grant/Research Support. Target RWE – Consultant. Techlab – Consultant. Trellus Health – Consultant.

Marc Fellmann: Pfizer Inc – Employee, Stock Options.

Sean Gardiner: Pfizer Inc – Employee, Stock Options, Stock-publicly held company(excluding mutual/index funds).

Jerome Paulissen: Pfizer Inc – Contractor. Syneos Health – Employee.

Majid A. Almadi indicated no relevant financial relationships.

Marla C. Dubinsky, MD¹, Luc Biedermann, MD², Ailsa Hart, MD³, Julian Panés, MD, PhD⁴, David T. Rubin, MD, FACG⁵, Marc Fellmann, PhD⁶, Sean Gardiner, MD⁷, Jerome Paulissen, MS⁷, Majid A. Almadi, MD⁸. C0364 - Assessment of Health-Related Quality of Life and Patient-Reported Outcomes With Tofacitinib Treatment Stratified by Age in Patients From the OCTAVE Ulcerative Colitis Clinical Program, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.