2120 The Journal of Rheumatology 2014; 41:11; doi:10.3899/jrheum.140238 Personal non-commercial use only. The Journal of Rheumatology Copyright © 2014. All rights reserved. A Phase III, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of 2 Dosing Regimens of Fostamatinib in Patients with Rheumatoid Arthritis with an Inadequate Response to a Tumor Necrosis Factor-α Antagonist Mark C. Genovese, Désirée M. van der Heijde, Edward C. Keystone, Alberto J. Spindler, Claude Benhamou, Arthur Kavanaugh, Edward Fudman, Kathy Lampl, Chris O’Brien, Emma L. Duffield, Jeffrey Poiley, and Michael E. Weinblatt 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. (First Release Sept 15 2014; J Rheumatol 2014;41:2120–8; doi:10.3899/jrheum.140238) Key Indexing Terms: FOSTAMATINIB METHOTREXATE EFFICACY OSKIRA RHEUMATOID ARTHRITIS 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. Clinical study sponsored by AstraZeneca. M. Genovese has received research grants and consulting fees from AstraZeneca and Rigel. D. van der Heijde has received consulting fees from AbbVie, Amgen, AstraZeneca, Augurex, BMS, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli Lilly and Co., GSK, Janssen, Merck, Novartis, Novo Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB, and Vertex, and serves as director at Imaging Rheumatology BV. E. Keystone has obtained research grants from Abbott, Amgen, AstraZeneca, Baylis Medical, Bristol-Myers Squibb, Roche, Janssen, Eli Lilly and Co., Novartis, Pfizer, Sanofi-Aventis, and UCB. He also has consulting agreements and/or advisory board membership with Abbott, AstraZeneca, Biotest, Bristol-Myers Squibb, Roche, Genentech Inc., Janssen Inc., Eli Lilly and Co., Merck, Nycomed, Pfizer, and UCB, and speaker honoraria agreements with Abbott, AstraZeneca, Bristol-Myers Squibb, Roche Inc., Janssen Inc., Pfizer, UCB, and Amgen. A. Spindler is a clinical study investigator for AstraZeneca. C. Benhamou has received research grants from Servier and Amgen and consulting fees from RottaPharm, and has held nonremunerative positions of influence for Novartis and Roche. A. Kavanaugh has received research grants from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Roche, Janssen, Novartis, Pfizer, Sanofi-Aventis, and UCB. E. Fudman has received research grants from AstraZeneca, Astellas, Bristol-Myers Squibb, Genentech, Pfizer, and Sanofi-Aventis. E.L. Duffield is an employee of AstraZeneca and holds stocks/shares in AstraZeneca. K. Lampl and C. O’Brien are former employees of AstraZeneca and hold stocks/shares in AstraZeneca. J. Poiley has received research grants from AstraZeneca. M. Weinblatt has received research grants from Crescendo Bioscience, Bristol-Myers Squibb and UCB, has received consulting fees from AbbVie, Ablynx, Adheron Therapeutics, Amgen, Antares, AstraZeneca, Augurex, Bristol-Myers Squibb, Canfite, Crescendo Bioscience, Ensemble, Exagen, Five Prime, Genentech/Roche, Hutchison, Idera, Infinity, Janssen, Lycera, Lilly, Medimmune, Merck, Novo Nordisk, Pfizer, Regeneron, UCB and Vertex, and holds stocks/shares in Canfite, Ensemble and Lycera. 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, www.jrheum.org Downloaded on February 22, 2022 from