IBD

13 - Tofacitinib, an Oral Janus Kinase Inhibitor, in the Treatment of Ulcerative Colitis: An Interim Analysis of an Open-Label, Long-Term Extension Study With up to 4.9 Years of Treatment

Monday, October 8
2:35 PM - 2:45 PM
Location: Terrace Ballroom 4 (level 400)

Category: IBD
Gary R. Lichtenstein, MD1, Edward V. Loftus, Jr., MD2, Stuart Bloom, DM, FRCP3, Nervin Lawendy, PharmD4, Gary Chan, PharmD4, Gary S. Friedman, MD4, Haiying Zhang, PhD4, Wenjin Wang, PhD4, Andrew J. Thorpe, PhD4, Chudy I. Nduaka, DVM, PhD4, Chinyu Su, MD4
1Hospital of the University of Pennsylvania, Philadelphia, PA; 2Mayo Clinic, Rochester, MN; 3University College London Hospitals NHS Foundation Trust, London, England, United Kingdom; 4Pfizer Inc., Collegeville, PA

Introduction: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). The efficacy and safety of tofacitinib was demonstrated as induction and maintenance therapy in patients (pts) with moderate to severe UC in 3 Phase 3, randomized, placebo-controlled studies [1]. Safety and efficacy of tofacitinib for UC are being evaluated in an ongoing, open-label, long-term extension (OLE) study [2].

Methods: We present an update (as of Nov 10 2017) of previous safety and efficacy data [2] of the OLE study (NCT01470612) in completers or treatment failures in OCTAVE Sustain (NCT01458574) and non-responders in OCTAVE Induction 1/2. Eligibility was determined per Week (Wk) 8 data from OCTAVE Induction 1/2, or Wk 52 data (for completers) or early termination data from OCTAVE Sustain. Pts in remission (total Mayo score ≤2, no individual subscore >1, rectal bleeding subscore of 0) at Wk 52 of OCTAVE Sustain (per central read) were assigned to tofacitinib 5 mg twice daily (BID) in the OLE study; all others were assigned to 10 mg BID. At Month 2, all pts underwent endoscopy; induction non-responders were mandated to withdraw if they did not show a clinical response. Binary efficacy endpoints were derived from Mayo score per local read.

Results: Of 944 pts who received ≥1 dose of study drug (for up to 4.9 years), 326 (34.5%) discontinued due to insufficient clinical response, and 65 (6.9%) due to adverse events (AEs) excl. worsening UC. Serious and severe AEs occurred in 14.8% and 9.9% of pts, respectively. Serious infections were reported in 5 (2.9%) and 23 (3.0%) pts, herpes zoster in 10 (5.7%) and 47 (6.1%) pts, and major adverse cardiovascular events in 1 (0.6%) and 1 (0.1%) pts, in the 5 and 10 mg BID groups, respectively. Malignancies excl. non-melanoma skin cancer (NMSC) were reported in 1 (0.6%) and 12 (1.6%) pts, and NMSC in 4 (2.3%) and 9 (1.2%) pts, in the 5 and 10 mg BID groups, respectively (no clustering of malignancy type). No new safety risks were identified. Available efficacy data up to Month 24 are shown (Table).

Discussion: In pts with moderate to severe UC in the OLE study, no new safety risks emerged compared with those observed with tofacitinib in rheumatoid arthritis. Efficacy data from the OLE study continue to support long-term efficacy with tofacitinib 5 or 10 mg BID up to 24 months beyond Wk 52 of OCTAVE Sustain.

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

2. Lichtenstein et al. Am J Gastroenterol 2017;112(S1):714.


Disclosures:
Gary Lichtenstein: AbbVie – Consultant. Actavis – Consultant. Alaven – Consultant. American Regent – Consultant. Celgene – Consultant. Cellceutix – Consultant. Ferring – Consultant. Gilead – Consultant. Hospira – Consultant. Pfizer Inc – Consultant. Prometheus Laboratories Inc – Consultant. Romark – Consultant. Salix Pharmaceuticals – Consultant. Shire Pharmaceuticals – Consultant. Takeda – Consultant. UCB – Consultant.
Edward Loftus: Abbvie – Consultant, Grant/Research Support. Amgen – Consultant, Grant/Research Support. Celgene – Consultant, Grant/Research Support. Celltrion Healthcare – Consultant. Eli Lilly – Consultant. Genentech – Grant/Research Support. Gilead – Grant/Research Support. Janssen – Consultant, Grant/Research Support. MedImmune – Grant/Research Support. Napo Pharma – Consultant. Pfizer Inc – Consultant, Grant/Research Support. Robarts Clinical Trials – Grant/Research Support. Seres – Grant/Research Support. Takeda – Consultant, Grant/Research Support. UCB – Consultant, Grant/Research Support.
Stuart Bloom: Abbvie – Advisory Committee/Board Member. Janssen – Advisory Committee/Board Member. Pfizer Inc – Advisory Committee/Board Member. Takeda – Advisory Committee/Board Member.
Nervin Lawendy: Pfizer Inc – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Gary Chan: Pfizer Inc – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Gary Friedman: Pfizer Inc – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Haiying Zhang: Pfizer Inc – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Wenjin Wang: Pfizer Inc – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Andrew Thorpe: Pfizer Inc – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Chudy Nduaka: Pfizer Inc – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Chinyu Su: Pfizer Inc – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).

Gary R. Lichtenstein

Professor of Medicine
University of Pennsylvania Perelman School of Medicine
Philadelphia, Pennsylvania

Gary R. Lichtenstein, MD, FACG, is Director, IBD Center, Professor of Medicine, at the Hospital of the University of Pennsylvania and the University of Pennsylvania School of Medicine. He earned his MD from the Mount Sinai School of Medicine in NY; his internship and residency in internal medicine were conducted at Duke University Medical Center, and he completed his fellowship in gastroenterology at the University of Pennsylvania School of Medicine. His current research focuses on investigational therapies for IBD. A Fellow of the ACG, AGA, and ACP, he has been listed in "Best Doctors in America" (IBD), and was Medical Secretary for the ABIM, GI Section. In the AGA, he was Vice-Chair for the Clinical Practice Committee and Practice Economics Committee, and was Chair of the Clinical Practice Committee. He served on the ASGE committee on training, as well as the ACG's Education Committee, Programs Committee, Nominations Committee, and Research Committee. He was Chair of the CCFA's Membership Committee of the Clinical Research Alliance, served on the national grants review committee and national physician education committee. He is a longstanding member of the ACP and AMA. Dr. Lichtenstein has received numerous awards, including the top specialist award at the University of Pennsylvania, the Louis A. Duhring Award, and the Christina and Marie Lindback Award, the top teaching award at the University of Pennsylvania. He has received the University of Pennsylvania's Department of Medicine Housestaff teaching award, the "Penn Pearls Award," and the Gastroenterology Division teaching award (Sidney Cohen Teaching Award). He is in "The Best Doctors in America" (IBD), and Philadelphia Magazine. He received the CCFA National Clinical Scientific Achievement Award. In addition to being an invited lecturer at over 400 national / international conferences, symposia and institutional grand rounds, he has authored over 350 peer-reviewed primary articles, chapters letters, and editorials, and presented more than 300 abstracts / 20 books.

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13 - Tofacitinib, an Oral Janus Kinase Inhibitor, in the Treatment of Ulcerative Colitis: An Interim Analysis of an Open-Label, Long-Term Extension Study With up to 4.9 Years of Treatment



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