Fostamatinib, an oral spleen tyrosine kinase inhibitor, in the treatment of rheumatoid arthritis: a meta-analysis of randomized controlled trials.
Fostamatinib is a selective inhibitor of spleen tyrosine kinase which has a role in the pathogenesis of RA. Multiple RCTs have been performed to study the effects of fostamatinib. The objective of this study was to perform a meta-analysis to analyze the efficacy and safety of fostamatinib in the management of RA. We searched PubMed, EMBASE and Cochrane CENTRAL through 11/9/15. Random effect model was used to estimate odds ratio (OR) and 95 % confidence interval. We measured outcomes with efficacy analysis using ACR20/50/70 response criteria and safety with adverse events. Five studies were included in the meta-analysis with total of 2105 patients including 1419 in fostamatinib group and 686 in placebo. Fostamatinib was effective in achieving ACR20, ACR50 and ACR70 responses compared to placebo (48 vs. 32.8 %, OR 1.86, 95 % CI 1.32-2.62, P = 0.0004, I (2) 63 %; 26.4 vs. 12.5 %, OR 2.50, 95 % CI 1.93-3.23, P < 0.00001, I (2) 0 % and 12.7 vs. 4.4 %, OR 3.00, 95 % CI 1.99-4.51, P < 0.00001, I (2) 0 %, respectively). Response to fostamatinib was rapid and significant effect on ACR20 response was seen by week 1 (OR 3.70, 95 % CI 2.33-5.87, P < 0.00001, I (2) 42 %). Safety analysis showed an increased risk of infection (OR 1.59, 95 % CI 1.2-2.11; P = 0.001; I (2) 0 %), diarrhea (OR 3.54; 95 % CI 2.43-5.16; P < 0.00001; I (2) 2 %), hypertension (OR 2.55, 95 % CI 1.54-4.22, P = 0.0003; I (2) 42 %) and neutropenia (OR 5.68, 95 % CI 1.97-16.42, P = 0.001, I (2) 35 %) and showed a trend toward the increase in ALT ≥3 times ULN (OR 1.76, 95 % CI 0.99-3.13; P = 0.05; I (2) 0 %). This meta-analysis concludes that fostamatinib has moderate effect in the treatment of RA with mostly mild-to-moderate adverse events and dose-dependent, transient neutropenia and hypertransaminasemia.
Department of Medicine, Lakes Region General Hospital, University of New England, 80 Highland Street, Laconia, NH, 03246, USA. sumitkunwar732@gmail.com.
Sumit
S
Kunwar
Division of Hospital Medicine, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA.
Ashok Raj
AR
Devkota
Department of Medicine, Interfaith Medical Center, Brooklyn, NY, USA.
Dipesh K C
DK
Ghimire
D000631:Aminopyridines; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D006801:Humans; D009025:Morpholines; D010078:Oxazines / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D011743:Pyrimidines; D016896:Treatment Outcome
D000631:Aminopyridines; D018501:Antirheumatic Agents; D009025:Morpholines; D010078:Oxazines; D011725:Pyridines; D011743:Pyrimidines; C523665:fostamatinib
Fostamatinib; Rheumatoid arthritis; SYK inhibitor