ABSTRACT: OBJECTIVE.: To assess the efficacy and safety of R788 (Fostamatinib disodium), an inhibitor of Spleen tyrosine kinase (Syk), in patients with active RA who failed biologic therapies. METHODS.: A total of 229 patients with active RA who had currently or previously failed a biologic therapy were enrolled in a 3-month double-blind, placebo-controlled trial of R788. The primary endpoint was the ACR 20 response at Month 3. Secondary endpoints included changes in inflammation and damage assessed by MRI, and changes in DAS. RESULTS.: The ACR 20 response in the R788 100mg BID group was 38% versus 37% in the placebo group at month 3. No significant differences were achieved in the ACR 20/50/70 levels at 3 months. There were differences between the groups in secondary endpoints from Baseline to month 3 in CRP and synovitis scores on MRI. There were baseline differences in steroid use, prior biologic use, and synovitis scores by MRI between R788 group versus placebo which may have affected the outcomes. A high placebo response rate was seen in this trial and exploratory analysis suggests this may in part have been driven by patients who entered the trial with an elevated ESR, but normal CRP. CONCLUSIONS.: No differences in the primary endpoint were seen between the R788 and placebo groups. Differences between the R788 and placebo groups were observed in secondary endpoints, particularly in those patients who entered with an elevated CRP. (ClinicalTrials.Gov Number: NCT00665926).
Arthritis & Rheumatism 10/2010; · 7.87 Impact Factor