OSKIRA-4: a phase IIb randomised, placebo-controlled study of the efficacy and safety of fostamatinib monotherapy
- Peter C Taylor1,
- Mark C Genovese2,
- Mike Greenwood3,
- Meilien Ho3,
- Evgeny Nasonov4,
- Barry Oemar5,
- Rumen Stoilov6,
- Jiri Vencovsky7,
- Michael Weinblatt8
- 1Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
- 2Department of Medicine, Stanford University, Stanford, California, USA
- 3AstraZeneca R&D, Macclesfield, UK
- 4Institute of Rheumatology, Russian Academy of Medical Sciences, Moscow, Russian Federation
- 5Formerly-AstraZeneca R&D, Boston, Massachusetts, USA
- 6Department of Rheumatology, University Hospital (MHAT) St. Ivan Rilski, Sofia, Bulgaria
- 7Institute of Rheumatology, Charles University, Prague, Czech Republic
- 8Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA
- Correspondence to Professor Peter C Taylor, Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford Botnar Research Centre, Windmill Road, Headington, Oxford OX3 7LD, UK;
- Received 6 February 2014
- Revised 30 May 2014
- Accepted 11 July 2014
- Published Online First 29 July 2014
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.