Efficacy and safety of romiplostim and eltrombopag in management of thrombocytopenia in Wiskott-Aldrich syndrome patients.

Wiskott-Aldrich syndrome (WAS) is a life-threatening inborn error of immunity associated with bleeding risk due to profound thrombocytopenia. We previously demonstrated that romiplostim is effective for thrombocytopenia treatment in 60% of WAS patients. In this prospective trial, 28 WAS patients (aged 0-17 years) were treated with thrombopoietin receptor agonists (TPO-RAs) to evaluate the comparative efficacy and safety of romiplostim versus eltrombopag and to assess the benefit of switching these molecules in individual subjects. We demonstrate that both drugs are effective, with the probability of achieving an overall platelet response (complete response-platelet count of 100 × 10⁹/L or more and partial response-platelet count increase of 30 × 10⁹/L or higher above baseline) of 73% for romiplostim and 43% for eltrombopag. Switching to an alternative TPO-RA allowed the achievement of a complete platelet response in 33% of patients after switching to eltrombopag and in 43% after romiplostim initiation. The cumulative efficacy of TPO-RAs, taking into account alternative therapy, was 87%. There was a grade 2 adverse event (AE) and a severe grade 4 AE related to eltrombopag-reversible acute liver failure associated with metabolic acidosis and encephalopathy. TPO-RAs proved to be an effective treatment for WAS patients waiting for stem cell transplantation or opting for a conservative treatment.