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Ann Rheum Dis doi:10.1136/annrheumdis-2014-205361
  • Clinical and epidemiological research
  • Extended report

OSKIRA-4: a phase IIb randomised, placebo-controlled study of the efficacy and safety of fostamatinib monotherapy

  1. Michael Weinblatt8
  1. 1Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
  2. 2Department of Medicine, Stanford University, Stanford, California, USA
  3. 3AstraZeneca R&D, Macclesfield, UK
  4. 4Institute of Rheumatology, Russian Academy of Medical Sciences, Moscow, Russian Federation
  5. 5Formerly-AstraZeneca R&D, Boston, Massachusetts, USA
  6. 6Department of Rheumatology, University Hospital (MHAT) St. Ivan Rilski, Sofia, Bulgaria
  7. 7Institute of Rheumatology, Charles University, Prague, Czech Republic
  8. 8Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA
  1. 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; peter.taylor{at}kennedy.ox.ac.uk
  • Received 6 February 2014
  • Revised 30 May 2014
  • Accepted 11 July 2014
  • Published Online First 29 July 2014

Abstract

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.