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

• Published in: Journal of rheumatology 2014-11, Vol.41 (11), p.2120-2128
• Main Authors: Genovese, Mark C, van der Heijde, Désirée M, Keystone, Edward C, Spindler, Alberto J, Benhamou, Claude, Kavanaugh, Arthur, Fudman, Edward, Lampl, Kathy, O'Brien, Chris, Duffield, Emma L, Poiley, Jeffrey, Weinblatt, Michael E
• Format: Article
• Language: English
• Subjects: Adult; Arthritis, Rheumatoid - diagnosis; Arthritis, Rheumatoid - drug therapy; Disease Progression; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Humans; Maximum Tolerated Dose; Methotrexate - adverse effects; Methotrexate - therapeutic use; Middle Aged; Oxazines - adverse effects; Oxazines - therapeutic use; Patient Safety; Prognosis; Pyridines - adverse effects; Pyridines - therapeutic use; Risk Assessment; Severity of Illness Index; Treatment Outcome; Tumor Necrosis Factor-alpha - antagonists & inhibitors
• ISSN: 0315-162X; 1499-2752
• DOI: 10.3899/jrheum.140238

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. 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. 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. 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.