OBJECTIVES: OSKIRA-4 evaluated the efficacy of fostamatinib monotherapy versus placebo on the signs and symptoms of rheumatoid arthritis over 6 weeks by Disease Activity Score C reactive protein (DAS-28(CRP)) and assessed non-inferiority to adalimumab monotherapy at Week 24 by DAS-28(CRP). METHODS: Overall, 279 patients not currently taking disease-modifying antirheumatic drugs were randomised to: (A) fostamatinib 100 mg twice daily for 24 weeks plus placebo injection every 2 weeks (PBOI); (B) fostamatinib 100 mg twice daily for 4 weeks, then 150 mg once daily up to Week 24, plus PBOI; (C) fostamatinib 100 mg twice daily for 4 weeks, then 100 mg once daily up to Week 24, plus PBOI; (D) adalimumab 40 mg every 2 weeks for 24 weeks, plus oral placebo twice daily; or (E) oral placebo twice daily for 6 weeks, plus PBOI, then a switch to arm A or B. RESULTS: Fostamatinib demonstrated a significant improvement in DAS-28(CRP) score from baseline versus placebo at Week 6 for arms A and B, but not C. Fostamatinib was significantly less effective than adalimumab at Week 24 based on DAS-28(CRP). Adverse events observed with fostamatinib treatment were consistent with those reported in previous studies, including hypertension and diarrhoea. CONCLUSIONS: Fostamatinib demonstrated efficacy as monotherapy, showing superior DAS-28(CRP) score changes between baseline and 6 weeks when compared with placebo in treatment arms A and B. However, all fostamatinib regimens demonstrated inferior responses compared with adalimumab at Week 24. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT01264770.

AstraZeneca R and D Macclesfield UK

Department of Medicine Stanford University Stanford California USA

Department of Rheumatology University Hospital St Ivan Rilski Sofia Bulgaria

Division of Rheumatology Immunology and Allergy Brigham and Women's Hospital Boston Massachusetts USA

Formerly AstraZeneca R and D Boston Massachusetts USA

Institute of Rheumatology Charles University Prague Czech Republic

Institute of Rheumatology Russian Academy of Medical Sciences Moscow Russian Federation

Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences University of Oxford Oxford UK

Citace poskytuje Crossref.org

Emerging Modes of Treatment of IgA Nephropathy

Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: Results of two phase 3, randomized, placebo-controlled trials

Zobrazit více v PubMed

ClinicalTrials.gov
NCT01264770