Effects of Intermittent Fasting on Patients with Immune Thrombocytopenia (ITP) Receiving TPO-RA : Multicenter Mixed-Design Study

Abstract

Introduction The thrombopoietin receptor agonists (TPO-RAs), such as Avatrombopag (AVA), Eltrombopag (ELT), and Romiplostim (ROM), have, in recent years, changed ITP treatment, showing that there is both increased platelet destruction and suboptimal platelet production in ITP. ELT and AVA are oral drugs, while ROM is subcutaneous, and studies have shown that absorption of ELT can be affected by meals. Thus, for optimum absorption, patients are counseled to take it on an empty stomach at least 1 hour before or 2 hours after a meal and at least 2 hours before and 4 hours after calcium-containing meals. However, in Muslim countries where the 16/8 type of intermittent fasting is practiced by religion, the scheduling of drug consumption can be affected. Objective The aim of this study is to evaluate the effect of fasting on patients with ITP receiving different Thrombopoietin receptor agonists (TPO-RAs) brands. Methods A Multicenter, mixed design study was performed in which we interviewed Muslim patients (n = 100) who were 18 years of age or older in Qatar, Kuwait, and Saudi Arabia and fasted Ramadan while receiving TPO-RA treatment between the years of 2015 and 2023. Clinical and biological parameters are recorded using using a standardized patient form. Fasting status was confirmed by a telephone call to each patient. Patients' responses were retrospectively evaluated before, during, and after Ramadan. A statistically significant result was identified with a P-value of < 0.05. Bleeding tendency was also evaluated as either no bleeding, minor cutaneous and mucosal bleeding, or life-threatening bleeding involving major organs (i.e., central nervous system, gastrointestinal, or genitourinary). Results A hundred patients were identified who matched our inclusion criteria for this study. Platelet responses were different among the 3 products, and statistical significance was attributed to the product's compromised efficacy due to disturbed meal schedules and decreased absorption. For patients on AVA, the drug efficacy was not directly affected by meal schedule and absorption but instead was affected by patient compliance. The mean platelet count before Ramadan was estimated at 146.11 ± 111.76, while during Ramadan it dropped to 131.7 ± 107.6. Whereas when comparing platelets before and after Ramadan, there was an insignificant difference 146.11 ± 111.76 vs. 134.17 ± 60.9. For patients on ELT, the mean platelet count before Ramadan was estimated at 120.02 ± 59.7, while during Ramadan it dropped to 100.8 ± 68.16. Whereas when comparing platelets before and after Ramadan, there was an insignificant difference 120.02 ± 59.7 vs. 136.04 ± 74.86. For patients on ROM, the mean platelet count before Ramadan was estimated at 122.68 ± 80.57, while during Ramadan it was 130.94 ± 84.96. Whereas when comparing platelets before and after Ramadan, there was an insignificant difference but an increase in platelet count 122.68 ± 80.57 vs 212.0 ± 113.72. Only 3% (3 patients on ELT) of the patients fasting during Ramadan experienced bleeding episodes. 2 of which experienced minor bleeding (ecchymosis and gingival bleeding), and 1 had major bleeding episodes (Lt. hemorrhagic infarction). 47% of the patients experienced a complete response (PLT>100x10 9) among the three products, and 17% experienced a partial response (PLT 51-100x10 9) 36.6% of the patients on AVA showed a complete response, 46.15% of patients on ELT, and 63.15% of patients on ROM. Conclusion TPO-RAs achieve target platelet counts in adult ITP patients. However, the absorption of ELT is highly affected by food consumption, and thus it is critical to adhere to the instructions given on how the dose should be adjusted and consumed on an empty stomach. AVA absorption didn't show compromise with food consumption, and its efficacy may depend only on patient's compliance. ROM showed better adherence to the medication schedule compared to ELT, contributing to its subcutaneous form and a tailored home visit program given weekly by trained nurses, enhancing patient compliance. The general tolerability and efficacy of TPO-RAs may be reflected on incidence of no major bleeding and the better efficacy of AVA and ROM, which are not affected by fasting.