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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F18%3A00068726" target="_blank" >RIV/65269705:_____/18:00068726 - isvavai.cz</a>

Výsledek na webu

<a href="https://onlinelibrary.wiley.com/doi/abs/10.1002/ajh.25125" target="_blank" >https://onlinelibrary.wiley.com/doi/abs/10.1002/ajh.25125</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/ajh.25125" target="_blank" >10.1002/ajh.25125</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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 &gt;= 50000/mu L at &gt;= 4 of 6 biweekly visits, weeks 14-24, without rescue therapy). Baseline median platelet count was 16000/mu L; 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 &gt;= 1 platelet count &gt;= 50000/mu L 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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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 &gt;= 50000/mu L at &gt;= 4 of 6 biweekly visits, weeks 14-24, without rescue therapy). Baseline median platelet count was 16000/mu L; 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 &gt;= 1 platelet count &gt;= 50000/mu L 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30205 - Hematology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

American journal of hematology

ISSN

0361-8609

e-ISSN

—

Svazek periodika

93

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

921-930

Kód UT WoS článku

000437829500020

EID výsledku v databázi Scopus

2-s2.0-85047461708