Mark C Genovese1, Désirée M van der Heijde2, Edward C Keystone2, Alberto J Spindler2, Claude Benhamou2, Arthur Kavanaugh2, Edward Fudman2, Kathy Lampl2, Chris O'Brien2, Emma L Duffield2, Jeffrey Poiley2, Michael E Weinblatt2. 1. From Stanford University, Palo Alto, California, USA; Leiden University Medical Center, Leiden, The Netherlands; University of Toronto, Toronto, Ontario, Canada; Centro Medico Privado de Reumatologia, San Miguel de Tucuman, Argentina; Centre Hospitalier Régional, Orleans, France; University of California, San Diego, La Jolla, California; Austin Rheumatology Research PA, Austin, Texas; (formerly) AstraZeneca, Wilmington, Delaware, USA; AstraZeneca, Macclesfield, UK; Arthritis Associates, Orlando, Florida; Brigham and Women's Hospital, Boston, Massachusetts, USA.M.C. Genovese, MD, Stanford University; D.M. van der Heijde, MD, PhD, Leiden University Medical Center; E.C. Keystone, MD, University of Toronto; A.J. Spindler, MD, Centro Medico Privado de Reumatologia; C. Benhamou, MD, Centre Hospitalier Régional; A. Kavanaugh, MD, University of California, San Diego; E. Fudman, MD, Austin Rheumatology Research PA; K. Lampl, MD; C. O'Brien, MD, PhD, (formerly) AstraZeneca; E.L. Duffield, MSc, AstraZeneca, UK; J. Poiley, MD, Arthritis Associates; M.E. Weinblatt, MD, Brigham and Women's Hospital. genovese@stanford.edu. 2. From Stanford University, Palo Alto, California, USA; Leiden University Medical Center, Leiden, The Netherlands; University of Toronto, Toronto, Ontario, Canada; Centro Medico Privado de Reumatologia, San Miguel de Tucuman, Argentina; Centre Hospitalier Régional, Orleans, France; University of California, San Diego, La Jolla, California; Austin Rheumatology Research PA, Austin, Texas; (formerly) AstraZeneca, Wilmington, Delaware, USA; AstraZeneca, Macclesfield, UK; Arthritis Associates, Orlando, Florida; Brigham and Women's Hospital, Boston, Massachusetts, USA.M.C. Genovese, MD, Stanford University; D.M. van der Heijde, MD, PhD, Leiden University Medical Center; E.C. Keystone, MD, University of Toronto; A.J. Spindler, MD, Centro Medico Privado de Reumatologia; C. Benhamou, MD, Centre Hospitalier Régional; A. Kavanaugh, MD, University of California, San Diego; E. Fudman, MD, Austin Rheumatology Research PA; K. Lampl, MD; C. O'Brien, MD, PhD, (formerly) AstraZeneca; E.L. Duffield, MSc, AstraZeneca, UK; J. Poiley, MD, Arthritis Associates; M.E. Weinblatt, MD, Brigham and Women's Hospital.
Abstract
OBJECTIVE: Our 24-week study (NCT01197755; OSKIRA-3) compared the efficacy and safety of fostamatinib versus placebo in patients taking background methotrexate treatment with active rheumatoid arthritis (RA) and an inadequate response to a single tumor necrosis factor-α antagonist. METHODS:Adult patients were randomized (1:1:1) to fostamatinib [100 mg bid for 24 weeks (n=105; Group A)], or 100 mg bid for 4 weeks, then 150 mg qd (n=108; Group B), or to placebo (n=110; Group C) for 24 weeks. Nonresponders at Week 12 could enter a longterm extension study. The primary endpoint was the proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at Week 24. RESULTS: Baseline characteristics were well balanced. Significantly more patients in fostamatinib Group A (36.2%; p=0.004), but not B (27.8%; p=0.168), achieved ACR20 at Week 24 versus placebo (21.1%). Frequently reported adverse events were diarrhea, hypertension, and headache. Elevated blood pressure (≥140/90 mm Hg) at ≥1 visit was observed in 46.7%, 51.9%, and 26.6% of patients, respectively. There were 2 deaths in the study, 1 in Group B and 1 in the placebo group. CONCLUSION: Fostamatinib 100 mg bid, but not fostamatinib 100 mg bid for 4 weeks then 150 mg qd, achieved statistical improvements in ACR20 at 24 weeks versus placebo. Because of efficacy and safety results from the phase III clinical program, the companies developing fostamatinib have decided not to study it further in RA at this time.
RCT Entities:
OBJECTIVE: Our 24-week study (NCT01197755; OSKIRA-3) compared the efficacy and safety of fostamatinib versus placebo in patients taking background methotrexate treatment with active rheumatoid arthritis (RA) and an inadequate response to a single tumor necrosis factor-α antagonist. METHODS: Adult patients were randomized (1:1:1) to fostamatinib [100 mg bid for 24 weeks (n=105; Group A)], or 100 mg bid for 4 weeks, then 150 mg qd (n=108; Group B), or to placebo (n=110; Group C) for 24 weeks. Nonresponders at Week 12 could enter a longterm extension study. The primary endpoint was the proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at Week 24. RESULTS: Baseline characteristics were well balanced. Significantly more patients in fostamatinib Group A (36.2%; p=0.004), but not B (27.8%; p=0.168), achieved ACR20 at Week 24 versus placebo (21.1%). Frequently reported adverse events were diarrhea, hypertension, and headache. Elevated blood pressure (≥140/90 mm Hg) at ≥1 visit was observed in 46.7%, 51.9%, and 26.6% of patients, respectively. There were 2 deaths in the study, 1 in Group B and 1 in the placebo group. CONCLUSION:Fostamatinib 100 mg bid, but not fostamatinib 100 mg bid for 4 weeks then 150 mg qd, achieved statistical improvements in ACR20 at 24 weeks versus placebo. Because of efficacy and safety results from the phase III clinical program, the companies developing fostamatinib have decided not to study it further in RA at this time.
Authors: Nichola Cooper; Ivy Altomare; Mark R Thomas; Phillip L R Nicolson; Steve P Watson; Vadim Markovtsov; Leslie K Todd; Esteban Masuda; James B Bussel Journal: Ther Adv Hematol Date: 2021-04-30
Authors: Dave Lengel; Eva Lamm Bergström; Herb Barthlow; Karen Oldman; Helen Musgrove; Alex Harmer; Jean-Pierre Valentin; Paul Duffy; Martin Braddock; Jon Curwen Journal: Pharmacol Res Perspect Date: 2015-09-15
Authors: Alexandra Lindau; Carmen Härdtner; Sonja P Hergeth; Kelly Daryll Blanz; Bianca Dufner; Natalie Hoppe; Nathaly Anto-Michel; Jan Kornemann; Jiadai Zou; Louisa M S Gerhardt; Timo Heidt; Florian Willecke; Serjosha Geis; Peter Stachon; Dennis Wolf; Peter Libby; Filip K Swirski; Clinton S Robbins; William McPheat; Shaun Hawley; Martin Braddock; Ralf Gilsbach; Lutz Hein; Constantin von zur Mühlen; Christoph Bode; Andreas Zirlik; Ingo Hilgendorf Journal: Basic Res Cardiol Date: 2016-02-18 Impact factor: 17.165