There has been one
publication on Fostamatinib at the ACR 2015 Annual Meeting in San Francisco. After
reading the study by M. Genovese and colleagues last year, I thought I’d never
hear anything on fostamatinib again; follow the link below for the whole story.
Let’s look at the study, I’ve found in the wake of this year’s ACR Meeting.
Cecilie F.
Kjelgaard-Petersen and colleagues presented: “The Active Metabolite of
Fostamatinib, R406, Only Decreases the Inflammation-Driven Extracellular Matrix
Turnover of the Joint at High Concentrations Ex Vivo”. Background/Purpose:
“Osteoarthritis (OA) and rheumatoid arthritis are degenerative diseases of the
whole joint. […]” I wouldn’t classify RA as a degenerative disease, though
mutilations might lead to further degeneration, also after successful therapy
and in the absence of autoimmune inflammation. But let’s move on. “Fostamatinib
has been tested in both phase II and phase III clinical trials with mixed
results.” Well, I'd call this statement euphemistic, but this view is possible. Methods: ”Cartilage turnover was investigated using a bovine
cartilage explant (BEX) model. […]” Conclusion: “These data show that R406 can
inhibit pro-inflammatory ECM joint degradation at concentrations higher than
0.5 μM, but at 0.5 μM or lower R406 increased the inflammatory degradation of
collagen type III and had no effect on aggrecan degradation. In contrast, the
p38 inhibitor SB203580 had no effect on synovial ECM turnover or aggrecan
degradation, underlining the importance of understanding the differences
between inhibitors of pro-inflammatory mediators and their effect on the joint
tissue.”
I think , we best sum it
up this way: good study to know more about “differences between inhibitors of
pro-inflammatory mediators and their effect on the joint tissue”, but I don’t
see anything, that could lead to putting fostamatinib back on the agenda concerning
rheumatoid arthritis.
References:
Kjelgaard-Petersen CF,
Thudium CS, Siebuhr AS, Christiansen TG, Karsdal MA, Hägglund P, Bay-Jensen AC.
The
Active Metabolite of Fostamatinib, R406, Only Decreases the Inflammation-Driven
Extracellular Matrix Turnover of the Joint at High Concentrations Ex Vivo [abstract].
Arthritis Rheumatol. 2015; 67 (suppl
10). http://acrabstracts.org/abstract/the-active-metabolite-of-fostamatinib-r406-only-decreases-the-inflammation-driven-extracellular-matrix-turnover-of-the-joint-at-high-concentrations-ex-vivo/.
Accessed November 20, 2015.
Fostamatinib in Rheumatoid
Arthritis
04.12.2015
Today I've read in the "Annals of the Rheumatic Diseases / The EULAR Journal" an article by P.C. Taylor and colleagues: "OSKIRA-4: a phase IIb randomised, placebo-controlled study of the efficacy and safety of fostamatinib monotherapy". 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." "The modest clinical resulta in all of the phase III studies have let to a decision by the companies developing fostamatinib to not submit a regulatoty filing for its use in RA." "The relevance of these findings for other more selective SYK inhibitors remains to be seen.
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