P1650 - Patient-Reported Outcome Improvement with Tofacitinib in the Ulcerative Colitis OCTAVE Clinical Program

Monday, October 25, 2021

10:30 AM – 4:15 PM PT

Location: Shoreline Exhibit Hall

Has Audio

Presenting Author(s)

David Hudesman, MD

New York University School of Medicine
New York, NY, United States

David Hudesman, MD¹, Joana Torres, ², Leonardo Salese, MD³, John C. Woolcott, PhD³, Rajiv Mundayat, MSc⁴, Chinyu Su, MD³, Mahmoud H. Mosli, ⁵, Jessica R. Allegretti, MD, MPH, FACG⁶
¹New York University School of Medicine, New York, NY; ²Hospital Beatriz Ângelo, Loures, Lisboa, Portugal; ³Pfizer Inc., Collegeville, PA; ⁴Pfizer Inc., New York, NY; ⁵King Abdulaziz University Hospital, Jeddah, Makkah, Saudi Arabia; ⁶Brigham & Women’s Hospital, Harvard Medical School, Boston, MA

Introduction: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of UC. The OCTAVE clinical program included Phase 3 induction (OCTAVE Induction 1&2, NCT01465763 and NCT01458951) and maintenance (OCTAVE Sustain, NCT01458574) studies, and an open-label, long-term extension study (OCTAVE Open, NCT01470612).^1,2 Stool frequency (SF) and rectal bleeding (RB) are important patient (pt)-reported outcomes (PROs) in measuring UC disease activity and treatment effect.

Methods: This post hoc analysis reports long-term PRO measurements of RB and SF in pts from the OCTAVE clinical program. Analyses included pts from OCTAVE Induction 1&2, OCTAVE Sustain (responders from OCTAVE Induction 1&2), and OCTAVE Open (subpopulation in remission at Week [Wk]52 of OCTAVE Sustain, regardless of treatment). OCTAVE Open data from the final analyses (Aug 2020) are shown to Month (M)48. Endpoints included Mayo RB subscore (RBS)=0, Mayo SF subscore (SFS)=0 and ≤ 1, and partial Mayo score (PMS) remission (PMS ≤ 2 with no individual subscore > 1); analysis was descriptive (observed case).

Results: After induction therapy, 62.8–64.0% of tofacitinib 10 mg BID-treated pts achieved RBS=0 vs 37.0–42.9% of placebo (PBO)-treated pts, and 55.4–60.9% of tofacitinib 10 mg BID-treated pts achieved SFS ≤ 1 (21.7–23.6% achieved SFS=0) vs 33.6–33.7% of PBO-treated pts (11.2–12.6% for SFS=0). Among OCTAVE induction responders re-randomized to maintenance therapy, 85.2%, 92.0%, and 94.5% of pts had RBS=0, 79.6%, 89.3%, and 88.2% had SFS ≤ 1, and 40.7%, 56.3%, and 51.2% had SFS=0 at Wk52 of OCTAVE Sustain for PBO, tofacitinib 5 mg BID, and tofacitinib 10 mg BID, respectively. Among pts who entered OCTAVE Open in remission and who were assigned to tofacitinib 5 mg BID, 93.5%, 95.7%, and 66.3% of pts maintained or achieved RBS=0, SFS ≤ 1, and SFS=0, respectively, at M48 of OCTAVE Open. Additionally, 94.6% of these pts maintained PMS remission (which includes RBS and SFS) at M48.

Discussion: Most pts with UC demonstrated improvements in RBS and SFS after tofacitinib induction therapy. Among induction responders, the majority of pts maintained normalization or improvement in RB and/or SF in OCTAVE Sustain and up to M48 of OCTAVE Open. These data show robust and sustained improvement in key UC PROs with tofacitinib.

References:

1. Sandborn et al. N Engl J Med 2017;376:1723-36

2. Lichtenstein et al. J Crohns Colitis 2020;14(S1):DOP61

			RBS=0, n (%)	SFS ≤ 1, n (%)	SFS=0, n (%)
OCTAVE Induction 1	PBO	Baseline (N=121) Wk8 (N=119)	2 (1.7) 44 (37.0)	14 (11.6) 40 (33.6)	0 (0.0) 15 (12.6)
OCTAVE Induction 1	Tofacitinib 10 mg BID	Baseline (N=475) Wk8 (N=450)	8 (1.7) 288 (64.0)	55 (11.6) 274 (60.9)	7 (1.5) 106 (23.6)
OCTAVE Induction 2	PBO	Baseline (N=112) Wk8 (N=98)	2 (1.8) 42 (42.9)	12 (10.7) 33 (33.7)	0 (0.0) 11 (11.2)
OCTAVE Induction 2	Tofacitinib 10 mg BID	Baseline (N=428) Wk8 (N=401)	10 (2.3) 252 (62.8)	54 (12.6) 222 (55.4)	7 (1.6) 87 (21.7)
OCTAVE Sustain^a	PBO	Baseline (N=198) Wk52 (N=54)	172 (86.9) 46 (85.2)	161 (81.3) 43 (79.6)	69 (34.8) 22 (40.7)
	Tofacitinib 5 mg BID	Baseline (N=198) Wk52 (N=112)	175 (88.4) 103 (92.0)	164 (82.8) 100 (89.3)	70 (35.4) 63 (56.3)
	Tofacitinib 10 mg BID	Baseline (N=197) Wk52 (N=127)	178 (90.4) 120 (94.5)	163 (82.7) 112 (88.2)	66 (33.5) 65 (51.2)
OCTAVE Open	Tofacitinib 5 mg BID^b	Baseline (N=175) M48 (N=92)^c	172 (98.3) 86 (93.5)	175 (100.0) 88 (95.7)	113 (64.6) 61 (66.3)

Table: Table. Improvements in RBS and SFS in the UC OCTAVE Clinical Program (FAS, Observed Case). Analyses included 596 (PBO, Nf121; tofacitinib 10 mg BID, Nf475) and 540 (PBO, Nf112; tofacitinib 10 mg BID, Nf428) pts from OCTAVE Induction 1&2, respectively, for 8 wks; 593 pts from OCTAVE Sustain (PBO, Nf198; tofacitinib 5 mg BID, Nf197; tofacitinib 10 mg BID, Nf198; for up to 52 wks); and 175 pts from OCTAVE Open (tofacitinib 5 mg BID, for up to 48 months). OCTAVE Open data are from the final analyses (Aug 2020). a.Pts were eligible to enroll in OCTAVE Sustain if they had achieved clinical response upon completion of OCTAVE Induction 1 or 2; these pts were re-randomized to receive PBO, tofacitinib 5 mg BID, or tofacitinib 10 mg BID (with a 1:1:1 allocation ratio) in OCTAVE Sustain; b.Pts in remission (total Mayo score ≤ 2, no individual subscore > 1, RBS of 0) at Wk52 of OCTAVE Sustain (central read) received tofacitinib 5 mg BID per protocol in OCTAVE Open; c.Data from OCTAVE Open are reported up to M48, as follow-up data were limited (≤ 40 pts) at M60 and beyond. BID, twice daily; FAS, full analysis set; M, Month; N, number of randomized pts in the total population; n, number of pts with the specified response within the given category; PBO, placebo; pts, patients; RBS, Mayo rectal bleeding subscore; SFS, Mayo stool frequency subscore; UC, ulcerative colitis; Wk/wk, Week/week

Disclosures:

David Hudesman: AbbVie – Advisory Committee/Board Member, Consultant. Bristol-Myers Squibb – Advisory Committee/Board Member, Consultant. Janssen – Advisory Committee/Board Member, Consultant, Grant/Research Support. Pfizer Inc – Consultant, Grant/Research Support. Takeda – Advisory Committee/Board Member, Consultant.

Joana Torres: Arena – Consultant. Galapagos – Consultant. Gilead Sciences – Consultant. Janssen – Consultant, Grant/Research Support, Other Financial or Material Support, lecture fees. Pfizer Inc – Consultant.

Leonardo Salese: Pfizer Inc – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).

John Woolcott: Pfizer Inc – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).

Rajiv Mundayat: Pfizer Inc – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).

Chinyu Su: Pfizer Inc – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).

Mahmoud Mosli: AbbVie – Other Financial or Material Support, lecture fees. Hikma – Other Financial or Material Support, lecture fees. Janssen – Other Financial or Material Support, lecture fees. Pfizer Inc – Other Financial or Material Support, lecture fees. Takeda – Grant/Research Support, Other Financial or Material Support, lecture fees.

Jessica Allegretti: Artugen – Consultant. Baccain – Consultant. Bristol-Myers Squibb – Consultant. Celgene – Consultant. Finch Therapeutics – Consultant. Iterative Scopes – Consultant. Janssen – Consultant. Merck – Grant/Research Support. Morphic – Consultant. Pandion – Consultant. Pfizer Inc – Consultant.

David Hudesman, MD¹, Joana Torres, ², Leonardo Salese, MD³, John C. Woolcott, PhD³, Rajiv Mundayat, MSc⁴, Chinyu Su, MD³, Mahmoud H. Mosli, ⁵, Jessica R. Allegretti, MD, MPH, FACG⁶. P1650 - Patient-Reported Outcome Improvement with Tofacitinib in the Ulcerative Colitis OCTAVE Clinical Program, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.