Dexamethasone combined with oseltamivir can effectively improve the efficacy of newly diagnosed ITP patients: the latest research results of Professor Ming Hou’s team

Recently, the team of Professor Ming Hou from Qilu Hospital of Shandong University reported the results of a multi-center, open-label, randomized, phase II clinical study for adults with primary immune thrombocytopenia (ITP).

This study aims to compare the efficacy and safety of dexamethasone combined with oseltamivir or dexamethasone as a single agent in the treatment of adult ITP patients, in order to optimize the first-line treatment plan for adult ITP.

Research background and purpose ITP is one of the common clinical autoimmune diseases.
Since ITP currently has no "gold standard" for diagnosis, it is necessary to exclude the influence of secondary factors in addition to routine blood tests and bone marrow smears.

At present, the main principle of ITP treatment is to raise platelets (PLT) to a safe level on the basis of minimizing the side effects of treatment, reduce bleeding events, and optimize the health-related quality of life of patients.

There are three common first-line treatment options: 1) intravenous infusion of gamma globulin (IVIG), which is usually used for specific situations such as emergency severe ITP; 2) oral high-dose dexamethasone; 3) prednisone.

Domestic and foreign research data show that oral high-dose dexamethasone has a quick onset, high complete remission (CR) rate, and good safety.
Therefore, domestic and foreign guidelines tend to recommend high-dose dexamethasone as the first-line treatment of ITP.

However, there are still some patients who cannot achieve long-term remission with dexamethasone alone, so more effective first-line treatment strategies need to be explored.

Oseltamivir is an inhibitor of influenza virus neuraminidase.

Previous preclinical studies have shown that oseltamivir can induce platelet responses in the treatment of ITP.

However, its clinical application prospects in patients with ITP are currently unclear.

Therefore, the team of Professor Ming Hou launched a multi-center, open-label, randomized phase II clinical trial comparing dexamethasone combined with oseltamivir and dexamethasone monotherapy in the treatment of adult newly diagnosed ITP.

Research methods The patients included in the study were newly diagnosed ITP patients aged ≥18 years from 5 tertiary medical centers in China.

The included subjects were randomly assigned (1:1) to the treatment group of dexamethasone combined with oseltamivir (specifically: dexamethasone 40mg, qd, PO×4d + oseltamivir 75mg, bid, PO×4d) Or dexamethasone monotherapy group (specifically: dexamethasone 40mg, qd, PO×4d).

The main endpoint of the study is the patient's 14-day initial overall response rate (ORR) and 6-month ORR.

CR is defined as PLT count ≥100×109/L and no bleeding symptoms.

Partial remission (PR) is defined as PLT count ≥30×109/L but <100×109/L, and at least double the baseline PLT count without bleeding symptoms.

Sustained response is defined as the treatment response obtained lasts for at least 6 months without any other ITP-related specific intervention.

Intention-to-treat (ITT) population analysis, including all patients who participated in random assignment and received the assigned interventions.

Research results In this study, 96 patients received random allocation, 47 patients in the dexamethasone combined with oseltamivir treatment group, and 49 patients in the dexamethasone monotherapy group.

A total of 90 patients were included in the ITT population analysis.

The median age of all patients was 42 years; the distribution of baseline characteristics between the two groups was basically balanced.

The dexamethasone combined with oseltamivir treatment group had a higher 14-day initial response rate (86% vs 66%, P=0.
030) and a higher 6-month sustained remission rate than the dexamethasone monotherapy group ( 53% vs 30%, P=0.
032).

However, during the 18-month observation period, the ORR duration of the two groups of patients was similar (logarithmic test P=0.
176); in addition, there was no significant difference between the median response duration of the two groups of patients. Further analysis showed that the median PLT count of patients in the dexamethasone combined with oseltamivir treatment group was significantly higher than that of the patients in the dexamethasone monotherapy group at almost all time points when they responded to treatment.

At a median follow-up time of 8 months, the incidence of adverse events (AE) in the dexamethasone combined with oseltamivir combined treatment group was 35% vs 26% in the dexamethasone monotherapy group, respectively.

Of the overall 90 patients, 2 patients discontinued treatment (Grade 3) due to serious adverse events (SAE); among them, 1 patient (2%) in the dexamethasone combined with oseltamivir treatment group developed systemic edema, dexamethasone One patient (2%) in the monotherapy group developed fever.

No grade 4 or 5 AEs were observed, and no treatment-related deaths occurred.

Research conclusions The research results show that combining oseltamivir on the basis of dexamethasone can improve the efficacy of adult newly diagnosed ITP patients, and the safety is controllable, suggesting that this combination program is expected to become the optimal choice for the first-line treatment of adult ITP.

References: Lu Sun, Juan Wang, Linlin Shao, et al.
Dexamethasone plus oseltamivir versus dexamethasone in treatment-naive primary immune thrombocytopenia: a multicentre, randomised, open-label, phase 2 trial.
Lancet Haematol.
2021 Apr;8(4 ):e289-e298.
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