P0564 - Persistence of Tofacitinib Treatment in Patients With Ulcerative Colitis Who Entered the Open-Label, Long-Term Extension Study, OCTAVE OPEN in Remission or With a Clinical Response

Sunday, October 24, 2021

3:30 PM – 7:00 PM PT

Location: Shoreline Exhibit Hall

Has Audio

Presenting Author(s)

Remo Panaccione, MD, FRCP

Inflammatory Bowel Disease Clinic, Gastrointestinal Research, Cumming School of Medicine, University of Calgary
Calgary, AB, Canada

Remo Panaccione, MD, FRCP¹, Maria T. Abreu, MD², Irina Lazariciu, ³, Rajiv Mundayat, MSc³, Nervin Lawendy, PharmD⁴, Leonardo Salese, MD⁴, John C. Woolcott, PhD⁴, Bruce E. Sands, MD, MS⁵, María Chaparro, MD, PhD⁶
¹Inflammatory Bowel Disease Clinic, Gastrointestinal Research, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; ²Crohn's and Colitis Center, University of Miami Miller School of Medicine, Miami, FL; ³Pfizer Inc., New York, NY; ⁴Pfizer Inc., Collegeville, PA; ⁵Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY; ⁶Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Madrid, Spain

Introduction: Drug survival in open-label, long-term extension (OLE) studies may provide important information on the long-term efficacy and tolerability of a therapy. Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of UC. Efficacy and safety were demonstrated in three Phase 3, randomized, PBO-controlled studies in patients (pts) with moderate to severe UC. A Phase 3, OLE study (OCTAVE Open, NCT01470612) included pts from OCTAVE Induction 1&2 and OCTAVE Sustain.

Methods: Data on the persistence of tofacitinib treatment in the OLE study for pts who had a clinical response at Week (Wk) 52 of treatment with tofacitinib 5 or 10 mg BID, or PBO, in OCTAVE Sustain were evaluated. Data were analyzed for all responder pts and by remission status: responders who were also in remission (remitters; assigned to tofacitinib 5 mg BID per OLE study protocol), and responders who were not in remission (responders/non-remitters) at OLE baseline (assigned to tofacitinib 10 mg BID per OLE study protocol) (Figure). Duration of treatment in the OLE study varied by pt.

Results: At baseline of the OLE study, there were 280 pts with a clinical response (all responders) which included 164 remitters and 116 responders/non-remitters who were treated for a maximum of 7 years in the OLE study (Table). Of these, 118 (42.1%) pts discontinued the OLE study (68/164 [41.5%] among remitters and 50/116 [43.1%] among responders/non-remitters) with a median time to discontinuation of 291 wks. Overall, the estimated 2- and 5-year tofacitinib persistence rates in the all-responder population were 73.9% and 54.5%, respectively. These rates were numerically higher in remitters (76.8% and 56.9%, respectively) vs responders/non-remitters (69.8% and 50.0%, respectively). During the OLE study, 43 (26.2%) remitters increased tofacitinib dose from 5 to 10 mg BID, and 15 (12.9%) responders/non-remitters decreased tofacitinib dose from 10 to 5 mg BID.

Discussion: With up to 7 years of follow-up, treatment persistence to tofacitinib was highest amongst pts who were responders/remitters compared with responders/non-remitters and the majority of pts continued to be on treatment at 5 years. Analyses are post hoc and limited by sample size. Further research will help to understand the reasons for continuation or discontinuation of tofacitinib treatment in pts with UC.

Figure: Figure. Tofacitinib treatment sequence for pts in the responder subpopulation including responders/remitters and responder/non-remitter subpopulations. Six pts who responded to tofacitinib induction treatment received a dose of 15 mg BID. Clinical response was defined as a decrease from induction study baseline total Mayo score of ≥ 3 points and ≥ 30%, with a decrease in rectal bleeding subscore of ≥ 1 point or an absolute rectal bleeding subscore of 0 or 1. Remission was defined as a total Mayo score of ≤ 2, with no individual subscore > 1 and a rectal bleeding subscore of 0. BID, twice daily; N, number of pts treated; pts, patients; Wk, Week

	Responders/ remitters (N=164)^a	Responders/ non-remitters (N=116)^b	All responders (N=280)^c
Male, n (%)^d	89 (54.3)	71 (61.2)	160 (57.1)
Mean age, years (SD)	44.6 (14.8)	42.7 (12.8)	43.8 (14.0)
Treatment history, n (%)^d Prior TNFi use Prior TNFi failure Prior immunosuppressant use Prior immunosuppressant failure	71 (43.3) 64 (39.0) 107 (65.2) 101 (61.6)	54 (46.6) 52 (44.8) 93 (80.2) 89 (76.7)	125 (44.6) 116 (41.4) 200 (71.4) 190 (67.9)
Oral corticosteroid use, n (%)^d	64 (39.0)	48 (41.4)	112 (40.0)
Endoscopic subscore of 2 at OLE baseline, n (%)^d,e	81 (49.4)	39 (33.6)	120 (42.9)
Probability of treatment persistence (95% CI)^f 24 months 60 months 72 months	76.8 (69.6, 82.6) 56.9 (48.3, 64.6) 52.1 (41.8, 61.4)	69.8 (60.5, 77.3) 50.0 (38.2, 60.8) 44.5 (29.9, 58.1)	73.9 (68.4, 78.7) 54.5 (47.6, 60.8) 48.8 (39.7, 57.2)
Dose increase from tofacitinib 5 to 10 mg BID, n (%)^g	43 (26.2)	6 (5.2)	49 (17.5)
Dose decrease from tofacitinib 10 to 5 mg BID, n (%)^g	0 (0.0)	15 (12.9)	15 (5.4)

Table: Table: Baseline Demographics and Persistence of Tofacitinib Treatment in the OLE Study for Pts who Enrolled With a Clinical Response. a.Pts with a CR.h and in remission.i at baseline of the OLE study; 163 pts were assigned to receive tofacitinib 5 mg BID and 1 pt (protocol deviation) was assigned to receive tofacitinib 10 mg BID in the OLE study; b.Pts with a CR.h but not in remission.i at baseline of the OLE study; 11 pts (protocol deviations) were assigned to receive tofacitinib 5 mg BID and 105 pts were assigned to receive tofacitinib 10 mg BID in the OLE study; c.All pts with a CR.h (including responders/remitters and responders/non-remitters) at baseline of the OLE study; 174 pts were assigned to receive tofacitinib 5 mg BID and 106 pts were assigned to receive tofacitinib 10 mg BID in the OLE study; d.Data from baseline of OCTAVE Induction 1 and 2; e.Central read; f.Persistence of treatment was calculated in days as the time from the first dose in the OLE study to the date of treatment discontinuation plus 1 day. Persistence of treatment was censored at the last dosing date for pts meeting censoring criteria; g.Tofacitinib dose adjustments are from the dose assigned at baseline of the OLE study and dose adjustment could occur after 8 wks of treatment in the OLE study. Tofacitinib dose could be adjusted from 5 to 10 mg BID for efficacy or adjusted from 10 to 5 mg BID after meeting specific laboratory abnormalities or other protocol-defined criteria regarding efficacy; h.CR was defined as a decrease from induction study baseline total Mayo score of ≥ 3 points and ≥ 30%, plus a decrease in rectal bleeding subscore of ≥ 1 point or an absolute rectal bleeding subscore ≤1; i.Remission was defined as a total Mayo score of ≤2 with no individual subscore > 1, and a rectal bleeding subscore of 0. BID, twice daily; CI, confidence interval; CR, clinical response; N, number of pts in analysis population; n, number of pts in given category, OLE, open-label, long-term, extension; pts, patients; SD, standard deviation; TNFi, tumor necrosis factor inhibitor; wk, week

Disclosures:

Remo Panaccione: Abbott – Consultant. AbbVie – Advisory Committee/Board Member, Consultant, Grant/Research Support, Other Financial or Material Support, speaker fees. Alimentiv (previously Robarts Clinical Trials, owned by Alimentiv Health Trust) – Consultant. Amgen – Advisory Committee/Board Member, Consultant. Arena – Advisory Committee/Board Member, Consultant, Other Financial or Material Support, speaker fees. AstraZeneca – Consultant. Boehringer Ingelheim – Consultant. Bristol-Myers Squibb – Advisory Committee/Board Member, Consultant. Celgene – Advisory Committee/Board Member, Consultant, Other Financial or Material Support, speaker fees. Celltrion – Advisory Committee/Board Member, Consultant. Cosmo – Consultant. Eisai – Consultant. Elan – Consultant. Eli Lilly – Advisory Committee/Board Member, Consultant, Other Financial or Material Support, speaker fees. Ferring Pharmaceuticals – Advisory Committee/Board Member, Consultant, Grant/Research Support, Other Financial or Material Support, speaker fees. Galapagos – Advisory Committee/Board Member, Consultant. Genentech – Advisory Committee/Board Member, Consultant. Gilead Sciences – Advisory Committee/Board Member, Consultant, Other Financial or Material Support, speaker fees. GSK – Advisory Committee/Board Member, Consultant. Janssen – Advisory Committee/Board Member, Consultant, Grant/Research Support, Other Financial or Material Support, speaker fees. Merck – Advisory Committee/Board Member, Consultant, Other Financial or Material Support, speaker fees. Mylan – Advisory Committee/Board Member, Consultant. Oppilan Pharma – Advisory Committee/Board Member, Consultant. Pandion – Advisory Committee/Board Member, Consultant. Pfizer Inc – Advisory Committee/Board Member, Consultant, Grant/Research Support, Other Financial or Material Support, speaker fees. Progenity – Consultant. Protagonist Therapeutics – Consultant. Roche – Consultant, Other Financial or Material Support, speaker fees. Sandoz – Advisory Committee/Board Member, Consultant, Other Financial or Material Support, speaker fees. Satisfai Health – Consultant. Schering-Plough – Consultant. Shire – Advisory Committee/Board Member, Consultant, Other Financial or Material Support, speaker fees. Sublimity – Advisory Committee/Board Member, Consultant. Takeda – Advisory Committee/Board Member, Consultant, Grant/Research Support, Other Financial or Material Support, speaker fees. Theravance Biopharma – Advisory Committee/Board Member, Consultant. UCB – Consultant.

Maria Abreu: AbbVie – Consultant, Grant/Research Support. Bellatrix Pharmaceuticals – Consultant. Bristol-Myers Squibb – Consultant, Grant/Research Support. Cosmo – Consultant. Eli Lilly – Consultant. Genentech – Grant/Research Support. Gilead Sciences – Consultant, Grant/Research Support. Imedex – Consultant. Janssen – Consultant, Grant/Research Support. Prometheus Bioscience – Consultant, Grant/Research Support. Takeda – Consultant, Grant/Research Support.

Irina Lazariciu: IQVIA – Employee, paid contractor to Pfizer Inc.

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

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

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

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

Bruce Sands: 4D Pharma – Other Financial or Material Support, personal fees. AbbVie – Other Financial or Material Support, personal fees. Abivax – Other Financial or Material Support, personal fees. Allergan – Other Financial or Material Support, personal fees. Amgen – Other Financial or Material Support, personal fees. Arena – Grant/Research Support, Other Financial or Material Support, personal fees. AstraZeneca – Other Financial or Material Support, personal fees. Baxalta Bioscience India – Other Financial or Material Support, personal fees. Boehringer Ingelheim – Other Financial or Material Support, personal fees. Boston Pharmaceuticals – Other Financial or Material Support, personal fees. Capella BioScience – Other Financial or Material Support, personal fees. Celgene – Grant/Research Support, Other Financial or Material Support, personal fees. Celltrion – Other Financial or Material Support, personal fees. Eli Lilly – Other Financial or Material Support, personal fees and non-financial support. F. Hoffmann-La Roche – Other Financial or Material Support, personal fees. Ferring Pharmaceuticals – Other Financial or Material Support, personal fees. Genentech – Other Financial or Material Support, personal fees. Gilead Sciences – Other Financial or Material Support, personal fees. GSK – Other Financial or Material Support, personal fees. Immunic – Other Financial or Material Support, personal fees. InDex Pharmaceuticals – Other Financial or Material Support, personal fees. Inotrem – Other Financial or Material Support, personal fees. Ironwood Pharmaceuticals – Other Financial or Material Support, personal fees. Janssen – Other Financial or Material Support, personal fees. Johnson & Johnson – Other Financial or Material Support, personal fees. Kallyope – Other Financial or Material Support, personal fees. Morphic Therapeutic – Other Financial or Material Support, personal fees. Oppilan Pharma – Other Financial or Material Support, personal fees. OSE Immunotherapeutics – Other Financial or Material Support, personal fees. Otsuka – Other Financial or Material Support, personal fees. Palatin Technologies – Other Financial or Material Support, personal fees. Pfizer Inc – Other Financial or Material Support, personal fees and non-financial support. Progenity – Other Financial or Material Support, personal fees. Prometheus Biosciences IBD – Other Financial or Material Support, personal fees. Prometheus Laboratories – Other Financial or Material Support, personal fees. Protagonist Therapeutics – Other Financial or Material Support, personal fees. Redhill Biopharma – Other Financial or Material Support, personal fees. Rheos Medicines – Other Financial or Material Support, personal fees. Salix – Other Financial or Material Support, personal fees. Seres – Other Financial or Material Support, personal fees. Shire – Other Financial or Material Support, personal fees. Sienna Biopharmaceuticals – Other Financial or Material Support, personal fees. Surrozen – Other Financial or Material Support, personal fees. Takeda – Other Financial or Material Support, personal fees. Target RWE – Other Financial or Material Support, personal fees. Theravance Biopharma R&D – Grant/Research Support, Other Financial or Material Support, personal fees. USWM Enterprises – Other Financial or Material Support, personal fees. Ventyx Biosciences – Stockholder/Ownership Interest (excluding diversified mutual funds), Other Financial or Material Support, personal fees. Viela Bio – Other Financial or Material Support, personal fees. Vivelix Pharmaceuticals – Other Financial or Material Support, personal fees.

María Chaparro: Gilead – Consultant. Janssen – Consultant. Pfizer Inc – Consultant. Takeda – Consultant.

Remo Panaccione, MD, FRCP¹, Maria T. Abreu, MD², Irina Lazariciu, ³, Rajiv Mundayat, MSc³, Nervin Lawendy, PharmD⁴, Leonardo Salese, MD⁴, John C. Woolcott, PhD⁴, Bruce E. Sands, MD, MS⁵, María Chaparro, MD, PhD⁶. P0564 - Persistence of Tofacitinib Treatment in Patients With Ulcerative Colitis Who Entered the Open-Label, Long-Term Extension Study, OCTAVE OPEN in Remission or With a Clinical Response, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.