Immune thrombocytopenia (ITP) is an autoimmune disorder that induces a decrease in the number of circulating platelets due to spleen destruction and inability of megakaryocytes to restore normal co...

https://journals.sagepub.com/doi/pdf/10.1177/2042098618769587

Eltrombopag in immune thrombocytopenia: efficacy review and update on drug safety.

Primary immune thrombocytopenia (ITP) is a bleeding disorder that conventionally has been treated with steroids or other immunosuppressive treatments. The introduction of thrombopoietin receptor agonists (TPO-RAs), which increase platelet production, dramatically changed the treatment landscape for ITP by providing patients with well-tolerated, long-term treatment options. Two TPO-RAs, eltrombopag and romiplostim, have been approved in the United States and European Union for the treatment of ITP. Some patients do not benefit from the first TPO-RA they receive, so it is assumed that the alternate TPO-RA would have the same outcome. However, eltrombopag and romiplostim have distinct pharmacodynamic and pharmacokinetic properties and may have different tolerability and efficacy in individual patients with ITP. Published retrospective studies showed that >75% of patients who switched to the alternate TPO-RA maintained or achieved a response with the new treatment. Notably, most patients who switched due to lack of efficacy with the first TPO-RA responded to the alternate TPO-RA, which demonstrates an absence of cross-resistance between the two drugs. Therefore, switching to the alternate TPO-RA if the first TPO-RA fails to demonstrate a response should be considered before the use of a less-preferable option.

https://journals.sagepub.com/doi/pdf/10.1177/2040620719837906

Switching thrombopoietin receptor agonist treatments in patients with primary immune thrombocytopenia

Purpose of reviewMedical therapies for the treatment of immune thrombocytopenia (ITP) complicating SLE are increasingly being investigated as alternatives to splenectomy and IVIG. The purpose of this review is to highlight the therapies that are utilized in the treatment of primary ITP and ITP secon

Treatment of primary and secondary immune thrombocytopenia

Very few data exist on when a particular thrombopoietin-receptor agonist (TPO-RA) is favored in clinical practice for the treatment of patients with immune thrombocytopenia (ITP), about novel risk factors for vascular events (VE) with these drugs, nor about predictive factors for therapy free responses (TFR). We conducted an observational, retrospective, long-term follow-up multicenter study from November 2016 to January 2018 of 121 adult ITP patients initiating TPO-RA between January 2012 to December 2014. Data reflected that a platelet count ≤25 × 109/l at the time when the TPO-RA was initiated was associated with a 2.8 higher probability of receiving romiplostim vs. eltrombopag (P = 0.010). VE on TPO-RA was related to previous neoplasia in patients over 65 years (50% vs. 2.2%, P < 0.001), and to previous splenectomy in younger patients (100% vs. 33%, P = 0.001). Receiving romiplostim as first TPO-RA with no subsequent TPO-RA switching was associated with a 50% likelihood of TFR after 2.9 years of therapy (3.3 years in chronic ITP patients). These real-world data help deciphering some areas of uncertainty, and offer insight into some of the most relevant challenges of ITP which may help clinicians make appropriate treatment decisions in the management of adult ITP patients with TPO-RA.

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Deciphering predictive factors for choice of thrombopoietin receptor agonist, treatment free responses, and thrombotic events in immune thrombocytopenia.

We aimed to assess the risk factors of venous thrombosis (VT) and arterial thrombosis (AT) in adults with primary immune thrombocytopenia (ITP), particularly in relation to treatments. The population comprised all incident primary ITP adults in France between 2009 and 2017 (FAITH cohort; NCT03429660) built in the national health database. Outcomes were the first hospitalisation for VT and AT. Multivariable Cox regression models included baseline risk factors, time-varying exposure to ITP drugs, splenectomy and to cardiovascular drugs. The cohort included 10 039 patients. A higher risk of hospitalisation for VT was observed with older age, history of VT, history of cancer, splenectomy [hazard ratio (HR) 3·23, 95% confidence interval (CI) 2·26-4·61], exposure to corticosteroids (HR 3·55, 95% CI 2·74-4·58), thrombopoietin-receptor agonists (TPO-RAs; HR 2·28, 95% CI 1·59-3·26) and intravenous immunoglobulin (IVIg; HR 2·10, 95% CI 1·43-3·06). A higher risk of hospitalisation for AT was observed with older age, male sex, a history of cardiovascular disease, splenectomy (HR 1·50, 95% CI 1·12-2·03), exposure to IVIg (HR 1·85, 95% CI 1·36-2·52) and TPO-RAs (HR 1·64, 95% CI 1·26-2·13). Rituximab was not associated with an increased risk. These findings help to estimate the risk of thrombosis in adult patients with ITP and to select treatment.

Risk factors of hospitalisation for thrombosis in adults with primary immune thrombocytopenia, including disease-specific treatments: a French nationwide cohort study.

Resume Introduction Le risque de thrombose sous agonistes du recepteur de la thrombopoietine (romiplostim, eltrombopag) chez des patients traites pour un purpura thrombopenique immunologique est mal apprecie en vie reelle de meme que les circonstances de survenue d’un evenement thrombotique et sa prise en charge. Les objectifs de cette etude etaient de preciser les facteurs de risque, les circonstances de survenue et la prise en charge des thromboses survenant sous agonistes au cours du purpura thrombopenique immunologique. Methode Etude multicentrique retrospective nationale francaise, incluant les cas signales aux centres regionaux de pharmacovigilance. Resultats Quarante et un cas de thromboses (13 arterielles) chez 36 patients (14 hommes et 22 femmes, âge median : 59 ans) ont ete inclus sur une periode de janvier 2009 a octobre 2015. Vingt patients etaient traites par romiplostim, 15 par eltrombopag et 1 patient recevait les deux medicaments. Trente-trois patients (92 %) avaient un autre facteur de risque de thrombose. Dix (28 %) avaient un antecedent de thrombose et 13 (36 %) avaient recu une perfusion d’immunoglobulines dans le mois precedent l’evenement thrombotique. Le taux plaquettaire median etait de 172 G/L (1 a 1049 G/l) ; 3 patients avaient des anticorps anti-phospholipides et 4 thrombophilies constitutionnelles de faible impact (mutation heterozygote du facteur V Leiden, elevation du facteur VIII, mutation heterozygote du gene MTHFR ) etaient notees ; 18 patients (50 %) etaient splenectomises. L’evolution de la thrombose etait favorable dans 22 cas (56 %) apres traitement par anticoagulants ou antiagregants avec un suivi moyen de 13 mois. Des manifestations hemorragiques sous traitement antiagregant ou anticoagulant ont ete observees chez 14 % des patients, dont 5 % etaient severes (1 deces d’hemorragie intracrânienne, 1 deces de choc hemorragique). Conclusion Une evaluation rigoureuse du risque thrombotique doit preceder l’instauration d’un traitement par agoniste du recepteur de la thrombopoietine. Le role des anticorps antiphospholipides ou d’une thrombophilie constitutionnelle reste a definir. Cette prescription doit etre evitee en cas d’antecedent thrombotique. L’evolution defavorable etait principalement secondaire a des sequelles ischemiques.

Thromboses sous agonistes du récepteur de la thrombopoïétine au cours du purpura thrombopénique immunologique. Étude rétrospective multicentrique en France

G. Bardy

Papers

Thromboses sous agonistes du récepteur de la thrombopoïétine au cours du purpura thrombopénique immunologique. Étude rétrospective multicentrique en France