title: Effects of fostamatinib, an oral spleen tyrosine kinase inhibitor, in rheumatoid arthritis patients with an inadequate response to methotrexate: results from a phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study.
abstract: OBJECTIVE
  This phase III, 52-week study compared fostamatinib with placebo (for 24 weeks) in patients with active rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) therapy.
  
  
  METHODS
  Patients taking MTX were randomized (1:1:1) to receive fostamatinib 100 mg twice daily for 52 weeks (group A), fostamatinib 100 mg twice daily for 4 weeks and then 150 mg once daily (group B), or placebo for 24 weeks and then fostamatinib 100 mg twice daily (group C). At week 24, the co-primary end points were change from baseline in the American College of Rheumatology 20% (ACR20) improvement response rates and change in the modified total Sharp/van der Heijde score of radiographic damage (SHS).
  
  
  RESULTS
  In this study, 918 patients were randomized and received ≥1 dose of study drug (fostamatinib or placebo); the demographic and baseline clinical characteristics were well balanced. Following treatment with both fostamatinib regimens, a statistically significant difference in the ACR20 improvement response was achieved at week 24 as compared with that in patients receiving placebo (49.0% [group A] and 44.4%, [group B] versus 34.2%; P < 0.001 and P = 0.006, respectively), but there was no statistically significant difference in the SHS between either fostamatinib group and placebo (P = 0.25 and P = 0.17, respectively). The most common adverse events in patients in groups A, B, and C were hypertension (15.8%, 15.1%, and 3.9%, respectively) and diarrhea (13.9%, 15.1%, and 3.9%, respectively). Elevated blood pressure (≥140/90 mm Hg) occurred at ≥1 visit in 44.2%, 41.6%, and 19.3% of patients in each respective group.
  
  
  CONCLUSIONS
  With the use of either fostamatinib regimen in patients with RA, statistically significant, but not clinically significant, improvements in the ACR20 improvement response over placebo were achieved at 24 weeks, whereas a significant difference in the SHS was not seen. The overall level of response to treatment with fostamatinib was lower than had been observed in the phase II program, but similar adverse events were reported.
authors.affiliation: Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Weinblatt
authors.forename: Mark C
authors.initials: MC
authors.lastname: Genovese
authors.forename: Meilien
authors.initials: M
authors.lastname: Ho
authors.forename: Sally
authors.initials: S
authors.lastname: Hollis
authors.forename: Krystyna
authors.initials: K
authors.lastname: Rosiak-Jedrychowicz
authors.forename: Arthur
authors.initials: A
authors.lastname: Kavanaugh
authors.forename: David S
authors.initials: DS
authors.lastname: Millson
authors.forename: Gustavo
authors.initials: G
authors.lastname: Leon
authors.forename: Millie
authors.initials: M
authors.lastname: Wang
authors.forename: Désirée
authors.initials: D
authors.lastname: van der Heijde
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000631:Aminopyridines; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D003967:Diarrhea / Q000139:chemically induced; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D009025:Morpholines; D010078:Oxazines / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000627:therapeutic use*; D011743:Pyrimidines; D000072377:Syk Kinase; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000631:Aminopyridines; D018501:Antirheumatic Agents; D047908:Intracellular Signaling Peptides and Proteins; D009025:Morpholines; D010078:Oxazines; D011725:Pyridines; D011743:Pyrimidines; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C523665:fostamatinib; D008727:Methotrexate