Dexamethasone plus oseltamivir versus dexamethasone in treatment-naive primary immune thrombocytopenia: a multicentre, randomised, open-label, phase 2 trial

Effect of oseltamivir phosphate versus placebo on platelet recovery and plasma leakage in adults with dengue and thrombocytopenia; a phase 2, multicenter, double-blind, randomized trial

“…This was further confirmed in a patient with anti-GP1b antibody-mediated ITP, in whom oseltamivir phosphate reduced desialylation of platelet glycoproteins [23]. Different retrospective studies in conditions with accelerated platelet clearance, such as anti-GPIb antibody-mediated ITP [22,23,25] or suspected influenza [24], and an open-label randomized trial in sepsis [26], have supported the notion that Neu-1 inhibition by oseltamivir increases platelet counts [23]. This was further supported by the results of a recent multicentre, randomized, open-label phase 2 trial, which showed that oseltamivir in combination with dexamethasone resulted in a better platelet response compared with dexamethasone alone in patients with ITP [25].…”

“…Different retrospective studies in conditions with accelerated platelet clearance, such as anti-GPIb antibody-mediated ITP [22,23,25] or suspected influenza [24], and an open-label randomized trial in sepsis [26], have supported the notion that Neu-1 inhibition by oseltamivir increases platelet counts [23]. This was further supported by the results of a recent multicentre, randomized, open-label phase 2 trial, which showed that oseltamivir in combination with dexamethasone resulted in a better platelet response compared with dexamethasone alone in patients with ITP [25]. Besides platelet neuraminidase, DENV NS1 has been shown to directly activate endothelial neuraminidases leading to disruption of endothelial glycocalyx components [28].…”

“…Data from preclinical studies regarding the required dose of oseltamivir to exert the desired platelet effects is limited. However, the fact that a standard dose of 75mg BID was sufficient in different observational and interventional studies to exert an effect on platelet number, as well as to reduce platelet desialylation (assessed by flow cytometry) in a chronic ITP patient, suggests that the standard oseltamivir phosphate dose is sufficiently high [25,26,27]. Fourth, we cannot exclude that oseltamivir prevents or limits the development of thrombocytopenia when given earlier in the course of DENV infection, although we consider this scenario unlikely given the complete absence of difference in platelet counts between the two groups in this study.…”

“…However, oseltamivir may also inhibit human endogenous neuraminidase involved in sialic acid metabolism [19], and as such extend the lifespan of platelets. Studies indeed showed a significant increase in platelet number in individuals prescribed oseltamivir for (suspected) influenza [20,21], and the successful use of oseltamivir to increase platelet numbers in immune thrombocytopenia (ITP) [22][23][24][25] and sepsis [26].…”

Novel therapies for immune thrombocytopenia

“…In a recent open‐label randomized prospective trial, newly diagnosed ITP patients were administered dexamethasone 40 mg a day for four days ( n = 47) or dexamethasone 40 mg a day for four days plus oseltamivir 75 mg daily ( n = 43) for 10 days. Patients failing to attain a target platelet count were allowed to receive one additional four‐day dexamethasone pulse in both groups and in the oseltamivir group a second 10‐day course could be given 130 . An overall response (platelet count >30 × 10 9 /l and at least doubling the baseline platelet count) at day 14 was seen in 66% (31/47) of those receiving only dexamethasone and in 86% (37/43) of those also receiving oseltamivir ( P = 0·03); there was no difference in response whether patients had antibody against GPIbα.…”