[FosD TASKi3]
>>Arthritis Rheum. 2011 Feb;63(2):337-45. doi: 10.1002/art.30114.
An oral Syk kinase inhibitor in the treatment of rheumatoid arthritis: A three-month randomized, placebo-controlled, phase II study in patients with active rheumatoid arthritis that did not respond to biologic agents.
Genovese MC, Kavanaugh A, Weinblatt ME, Peterfy C, Dicarlo J, White ML, O'Brien M, Grossbard EB, Magilavy DB.
Stanford University, Palo Alto, California. genovese@stanford.edu.
Abstract
OBJECTIVE: To assess the efficacy and safety of R788 (fostamatinib disodium), an inhibitor of spleen tyrosine kinase (Syk), in patients with active rheumatoid arthritis (RA) that did not respond to biologic therapies.
METHODS: A total of 219 patients with active RA in whom treatment with biologic agents had failed were enrolled in a 3-month multicenter, randomized, double-blind, placebo-controlled trial of R788. The primary end point was the percentage of patients who met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at month 3. Secondary end points included changes in inflammation and damage, as assessed by magnetic resonance imaging (MRI), and changes in the Disease Activity Score.
RESULTS: The ACR20 response in the R788 100 mg twice daily group was 38%, versus 37% in the placebo group, at month 3. No significant differences were achieved in the ACR20, ACR50, or ACR70 response levels at 3 months. There were differences between the groups from baseline to month 3 in the secondary end points C-reactive protein (CRP) level and synovitis score on MRI. There were baseline differences in steroid use, prior biologic use, and synovitis score on MRI between the R788 group and the placebo group that may have affected the outcomes. A high placebo response rate was seen in this trial, and exploratory analysis suggested that this may in part have been driven by patients who entered the trial with an elevated erythrocyte sedimentation rate but normal CRP level.
CONCLUSION: Our findings indicate that there were no differences in the primary end point between the R788 and placebo groups. Differences were observed between the R788 and placebo groups in secondary end points, particularly in those patients who entered the study with an elevated CRP level.<<
This echoes the finding you mentioned that patients with low CRP levels botched the ACR scores. But the "elevated erythrocyte sedimentation rate" is another data point, though it was implied in your Piper write-up. Which is to say, it appears FosD works better when the disease is in its acute phase in this TNF failure population. Have I got that takeaway right? If I do, what does that mean for commercialization?
en.wikipedia.org
At least the ESR test is cheap.
RIGL starting to get to interesting price levels, but I need to get a grip on the above issue.
Cheers, Tuck |
