Fostamatinib, an oral spleen tyrosine kinase inhibitor, in the treatment of rheumatoid arthritis: a meta-analysis of randomized controlled trials

Kunwar, Sumit; Devkota, Ashok Raj; Ghimire, Dipesh K. C.

doi:10.1007/s00296-016-3482-7

Cited by 36 publications

(35 citation statements)

References 40 publications

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“…In this context, it is remarkable that increased phospho‐Syk was found both in treatment‐naive RA patients and in patients receiving methotrexate or methotrexate and biologic agents . A recent meta‐analysis concluded that the Syk inhibitor fostamatinib has moderate effects in the treatment of RA, with mostly mild‐to‐moderate adverse events and dose‐dependent, transient neutropenia and hypertransaminasemia .…”

Section: Discussionmentioning

confidence: 99%

Enhanced Bruton's Tyrosine Kinase Activity in Peripheral Blood B Lymphocytes From Patients With Autoimmune Disease

Corneth

Verstappen

Paulissen

et al. 2017

Arthritis & Rheumatology

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Section: Discussionmentioning

confidence: 99%

Enhanced Bruton's Tyrosine Kinase Activity in Peripheral Blood B Lymphocytes From Patients With Autoimmune Disease

Corneth

Verstappen

Paulissen

et al. 2017

Arthritis & Rheumatology

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“…Of 16 patients, 8 (50%) achieved long‐term responses, with manageable adverse events (AEs) . Fostamatinib was also extensively studied in rheumatoid arthritis, demonstrating efficacy and establishing a safety profile in a total of more than 3000 patients . This report describes two identical, parallel, multicenter, randomized, double‐blind, placebo‐controlled, phase 3 studies comparing fostamatinib to placebo in 150 adults with persistent and primarily chronic ITP of very long‐lasting duration, who had failed a number of prior treatments.…”

Section: Introductionmentioning

confidence: 99%

Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: Results of two phase 3, randomized, placebo‐controlled trials

et al. 2018

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Spleen tyrosine kinase (Syk) signaling is central to phagocytosis‐based, antibody‐mediated platelet destruction in adults with immune thrombocytopenia (ITP). Fostamatinib, an oral Syk inhibitor, produced sustained on‐treatment responses in a phase 2 ITP study. In two parallel, phase 3, multicenter, randomized, double‐blind, placebo‐controlled trials (FIT1 and FIT2), patients with persistent/chronic ITP were randomized 2:1 to fostamatinib (n = 101) or placebo (n = 49) at 100 mg BID for 24 weeks with a dose increase in nonresponders to 150 mg BID after 4 weeks. The primary endpoint was stable response (platelets ≥50 000/μL at ≥4 of 6 biweekly visits, weeks 14‐24, without rescue therapy). Baseline median platelet count was 16 000/μL; median duration of ITP was 8.5 years. Stable responses occurred in 18% of patients on fostamatinib vs. 2% on placebo (P = .0003). Overall responses (defined retrospectively as ≥1 platelet count ≥50 000/μL within the first 12 weeks on treatment) occurred in 43% of patients on fostamatinib vs. 14% on placebo (P = .0006). Median time to response was 15 days (on 100 mg bid), and 83% responded within 8 weeks. The most common adverse events were diarrhea (31% on fostamatinib vs. 15% on placebo), hypertension (28% vs. 13%), nausea (19% vs. 8%), dizziness (11% vs. 8%), and ALT increase (11% vs. 0%). Most events were mild or moderate and resolved spontaneously or with medical management (antihypertensive, anti‐motility agents). Fostamatinib produced clinically‐meaningful responses in ITP patients including those who failed splenectomy, thrombopoietic agents, and/or rituximab. Fostamatinib is a novel ITP treatment option that targets an important mechanism of ITP pathogenesis.

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“…In a meta-analysis of five randomized clinical trials of fostamatinib in rheumatoid arthritis (n = 1419 receiving fostamatinib versus n = 686 on placebo), fostamatinib increased the risk of infections (25 versus 14.7%; p = 0.001), diarrhea (16.7 vs 5%; p < 0.00001); hypertension (17 vs 7.6%; p = 0.0003), and neutropenia (6.8 vs 0.8%; p = 0.001) [70]. Elevated blood pressure and rates of hypertension have been attributed to off-target effects of fostamatinib on VEGFR2, as described above.…”

Section: Safety and Tolerabilitymentioning

confidence: 99%

Fostamatinib for Persistent/Chronic Adult Immune Thrombocytopenia

Newland

McDonald

et al. 2017

Immunotherapy

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Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by phagocytosis and destruction of autoantibody-coated platelets via spleen tyrosine kinase (Syk)-mediated signal transduction in macrophages. Effectiveness of existing therapies varies, and even leading treatments (e.g., IVIg, splenectomy, rituximab, thrombopoietic agents) do not provide optimal management for a substantial number of patients with chronic ITP. Fostamatinib disodium is an orally-bioavailable investigational agent being developed for treatment of primary persistent/chronic adult ITP. Fostamatinib inhibits FcR-triggered, Syk-dependent cytoskeletal rearrangement during phagocytosis. Promising findings have been described in several autoimmune diseases, including rheumatoid arthritis, and sustained responses with manageable adverse events observed with ongoing treatment in patients with heavily treated chronic ITP. Fostamatinib represents an active therapy targeting a previously unexplored mechanism of ITP pathogenesis.

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Fostamatinib, an oral spleen tyrosine kinase inhibitor, in the treatment of rheumatoid arthritis: a meta-analysis of randomized controlled trials

Cited by 36 publications

References 40 publications

Enhanced Bruton's Tyrosine Kinase Activity in Peripheral Blood B Lymphocytes From Patients With Autoimmune Disease

Enhanced Bruton's Tyrosine Kinase Activity in Peripheral Blood B Lymphocytes From Patients With Autoimmune Disease

Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: Results of two phase 3, randomized, placebo‐controlled trials

Fostamatinib for Persistent/Chronic Adult Immune Thrombocytopenia

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