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Eltrombopag in inherited thrombocytopenias
Part 2 of the study
Six patients met the criteria for enrollment in part 2 of the study. Two of them did not consent to long-term treatment for logistic reasons, as they were not available to undergo the repeated visits planned by the study protocol. Thus, four patients entered part 2 (2 with MYH9-RD, 1 with WAS, 1 with ITGB3-RT). At baseline all of them had spon- taneous mucosal hemorrhages WHO grade 2 or 3 (epis- taxis, gum bleeding, menorrhagia, and/or hematochezia) (Table 5).
Primary endpoint
The outcome of part 2 of the study is summarized in Table 5 and Figure 2. Three patients completed the 16 weeks of therapy. All of them obtained a stable remission of mucosal bleeding throughout the treatment period. During eltrombopag administration, they experienced only very mild and occasional easy bruising (WHO grade 1), resulting in a minor response according to the study cri- teria. Concerning the patient with WAS, treatment was discontinued after 8 weeks because of exacerbation of cutaneous eczema (see below). During treatment, this patient obtained a complete remission of bleeding (WHO grade 0).
Eltrombopag dose and health-related quality of life
Two patients achieved a response with eltrombopag 25 mg/day, whereas two patients required 50 mg/day (Table 5, Figure 2).
The reduction of bleeding symptoms was associated with an overall increase in the scores obtained with the FACT-TH18 and FACIT-F questionnaires (Online Supplementary Table S9). The increase was evident in the two MYH9-RD patients presenting the highest degree of bleeding tendency at baseline (WHO grade 3), whereas the two other patients obtained mild or no improvements.
Exploratory endpoints
The thrombopoietin levels of the four patients did not change significantly during part 2 of the study. Platelet response to ADP and TRAP was assessed by flow cytome- try in the two MYH9-RD patients and the WAS patient and did not show any significant changes with long-term eltrombopag (data not shown).
Safety
The patient with WAS reported exacerbation of a pre- existing cutaneous eczema, which is a typical manifesta- tion of the genetic disease. For this reason, eltrombopag
Figure 2. Effects of treatments in part 1 and part 2 of the study in the four individuals who received long-term eltrombopag therapy. The figure summarizes the effects of eltrombopag administration on bleeding symptoms according to the World Health Organization (WHO) bleeding scale and on platelet count. Patients 1/1 and 12/10 have MYH9-related disease, patient 17/13 has ITGB3-RT, and patient 22/16 has Wiskott-Aldrich syndrome (see Table 5).
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