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Long-term fostamatinib treatment of adults with immune thrombocytopenia during the phase 3 clinical trial program.

ABSTRACT: Two randomized, double-blind, placebo-controlled studies demonstrated responses (?50?000/?L) to fostamatinib in adults with long-standing immune thrombocytopenia (ITP). The long-term safety and efficacy of fostamatinib were evaluated in a follow-on, open-label extension (OLE) study. Patients received double-blind fostamatinib in the randomized trials, and responders continued the same dose, 100 to 150?mg BID, in the OLE study. Nonresponders received 100?mg BID for 4?weeks and could escalate to 150?mg BID at week 4. Endpoints included stable response, platelet count ?50?000/?L at 4/6 biweekly (randomized trials) or 2/3 monthly visits (OLE), and overall response, ?1 platelet count ?50?000/?L during weeks 1 to 12. A total of 146 patients received fostamatinib including 123 in the OLE study. Median treatment duration was 6.7?months. Baseline median ITP duration was 8?years and median platelet count was 16?000/?L; prior treatments included thrombopoietic (TPO) agents (47%), splenectomy (35%), and rituximab (32%). Twenty-seven (18%) patients achieved a stable response with median duration of >28?months and a median platelet count of 89?000/?L. Sixty-four (44%) patients achieved an overall response (including stable responders) with a median platelet count of 63?000/?L and a median response duration of >28?months. Twenty-four of 71 (34%) patients who had failed TPO agents achieved overall responses to fostamatinib. The most common adverse events (AEs) were diarrhea, hypertension, nausea, epistaxis, and abnormal liver function tests. Most AEs were mild/moderate and resolved or were managed with dose reduction, dose interruption, and/or secondary medication. Almost half of the patients achieved an overall response, and most of these maintained their responses for >2 years. No new or increased frequency of AEs was seen at up to 31?months of treatment.

SUBMITTER: Bussel JB

PROVIDER: S-EPMC6594140 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Long-term fostamatinib treatment of adults with immune thrombocytopenia during the phase 3 clinical trial program.

Bussel James B JB Arnold Donald M DM Boxer Michael A MA Cooper Nichola N Mayer Jiri J Zayed Hany H Tong Sandra S Duliege Anne-Marie AM

American journal of hematology 20190313 5

Two randomized, double-blind, placebo-controlled studies demonstrated responses (≥50 000/μL) to fostamatinib in adults with long-standing immune thrombocytopenia (ITP). The long-term safety and efficacy of fostamatinib were evaluated in a follow-on, open-label extension (OLE) study. Patients received double-blind fostamatinib in the randomized trials, and responders continued the same dose, 100 to 150 mg BID, in the OLE study. Nonresponders received 100 mg BID for 4 weeks and could escalate to 1 ...[more]

PMID: 30784097

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Project description:BackgroundImmune thrombocytopenia (ITP) is an immune-mediated disease that results in low platelet counts. Despite appropriate treatment, many patients continue to experience refractory disease. Fostamatinib, an oral spleen tyrosine kinase (SYK) inhibitor, has emerged as a promising option for refractory ITP.ObjectiveThis meta-analysis aims to evaluate the efficacy and safety of fostamatinib compared to conventional therapy in adults aged ≥ 18 years with refractory ITP.Materials and methodsLiterature search was conducted in PubMed, Scopus, Embase, and clinicaltrials.gov databases from inception to March 31, 2024. Randomized controlled trials (RCTs) assessing the safety and efficacy of fostamatinib in adults with refractory ITP were included. Data extraction, risk of bias assessment, and statistical analysis were performed following PRISMA guideline.ResultsA total of 495 articles were screened, with three RCTs meeting the inclusion criteria. Fostamatinib therapy demonstrated superior efficacy in achieving stable platelet response by week 24 (ORR 0.80; 95%CI 0.72-0.88), platelet count ≥ 50,000/µL at weeks 12 (ORR 0.80; 95%CI 0.72-0.90) and week 24 (ORR 0.82; 95%CI 0.72-0.90). Additionally, fostamatinib improves platelet counts in subjects with a baseline count of < 15,000/µL. The Number Needed to Treat (NNT) was calculated as 10. Adverse effects include diarrhea (RR 2.32; 95%CI 1.11-4.84), hypertension (RR 2.33; 95%CI 1.00-5.43), and abnormal liver function tests (RR 4.18; 95% CI 1.00-17.48). Interestingly, the occurrences of nausea (RR 1.77; 95% CI 0.33-9.67) and rash (RR 2.28; 95% CI 0.50-10.29) did not achieve statistical significance.ConclusionThis meta-analysis provides robust evidence supporting the efficacy of fostamatinib in improving platelet counts and achieving therapeutic goals in adults with refractory ITP. However, fostamatinib's safety profile warrants consideration due to higher rates of diarrhea, hypertension, and abnormal liver function tests.

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Long-term fostamatinib treatment of adults with immune thrombocytopenia during the phase 3 clinical trial program.

Publications

Long-term fostamatinib treatment of adults with immune thrombocytopenia during the phase 3 clinical trial program.

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