title: OSKIRA-4: a phase IIb randomised, placebo-controlled study of the efficacy and safety of fostamatinib monotherapy.
abstract: OBJECTIVE
  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.
  
  
  BACKGROUND
  Clinicaltrials.gov: NCT01264770.
authors: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
authors: Peter C
authors: PC
authors: Taylor
authors: Department of Medicine, Stanford University, Stanford, California, USA.
authors: Mark C
authors: MC
authors: Genovese
authors: AstraZeneca R&D, Macclesfield, UK.
authors: Mike
authors: M
authors: Greenwood
authors: AstraZeneca R&D, Macclesfield, UK.
authors: Meilien
authors: M
authors: Ho
authors: Institute of Rheumatology, Russian Academy of Medical Sciences, Moscow, Russian Federation.
authors: Evgeny
authors: E
authors: Nasonov
authors: Formerly-AstraZeneca R&D, Boston, Massachusetts, USA.
authors: Barry
authors: B
authors: Oemar
authors: Department of Rheumatology, University Hospital (MHAT) St. Ivan Rilski, Sofia, Bulgaria.
authors: Rumen
authors: R
authors: Stoilov
authors: Institute of Rheumatology, Charles University, Prague, Czech Republic.
authors: Jiri
authors: J
authors: Vencovsky
authors: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors: Michael
authors: M
authors: Weinblatt
mesh_terms: D000068879:Adalimumab / Q000008:administration & dosage; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000631:Aminopyridines; D018501:Antirheumatic Agents / Q000008:administration & dosage; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D002097:C-Reactive Protein / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009025:Morpholines; D010078:Oxazines / Q000008:administration & dosage*; D011725:Pyridines / Q000008:administration & dosage*; D011743:Pyrimidines; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000631:Aminopyridines; D018501:Antirheumatic Agents; D009025:Morpholines; D010078:Oxazines; D011725:Pyridines; D011743:Pyrimidines; D002097:C-Reactive Protein; D000068879:Adalimumab; C523665:fostamatinib
keywords: Anti-TNF; DMARDs (synthetic); Rheumatoid Arthritis