The status of fostamatinib in the treatment of rheumatoid arthritis.
Fostamatinib (R788) is a prodrug rapidly converted to its active metabolite on oral administration. This (known as R406) is a potent inhibitor of spleen tyrosine kinase, required for the expression of a number of proinflammatory cytokines. Fostamatinib has shown significantly superior efficacy (when compared with placebo) in the control of patients with rheumatoid arthritis not responding to methotrexate in Phase II clinical trials. Treatment emergent adverse events with a higher frequency than in those on placebo included diarrhea, hypertension, urinary tract infections, neutropenia and elevated transaminases. The studied doses have shown a linear pharmacokinetic pattern and the administration of methotrexate does not affect it. Fostamatinib may have a role in the therapy of patients with rheumatoid arthritis with poor response to conventional therapy. If these results are confirmed once Phase III studies are completed, it may find a place in the evolving treatment algorithm for rheumatoid arthritis.
Department of Rheumatology, Hospital Aranda de la Parra, Hidalgo 329-704, León 37000, GTO, Mexico. jorgitomorales@prodigy.net.mx
Jorge
J
Morales-Torres
D000284:Administration, Oral; D000631:Aminopyridines; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology; D002986:Clinical Trials as Topic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors*; D009025:Morpholines; D010078:Oxazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011355:Prodrugs / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines; D000072377:Syk Kinase; D016896:Treatment Outcome
D000631:Aminopyridines; D018501:Antirheumatic Agents; D047908:Intracellular Signaling Peptides and Proteins; D009025:Morpholines; D010078:Oxazines; D011355:Prodrugs; D011725:Pyridines; D011743:Pyrimidines; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C523665:fostamatinib