Thrombopoietin receptor agonists and rituximab for treatment of pediatric immune thrombocytopenia: A systematic review and meta‐analysis of prospective clinical trials

Abstract

Background Children with immune thrombocytopenia (ITP) may require second‐line ITP therapies. The high remission rate in pediatric patients, need for extended‐duration use of thrombopoietin receptor agonists (TPO‐RAs), drug adherence, potential side effects, monitoring, and cost effectiveness are factors that should be considered in decision‐making about second‐line therapies. Rituximab (RTX) has been used off‐label for years to treat ITP but there are limited studies about its efficacy and safety in children. To date, no studies have directly compared TPO‐RAs with RTX for the treatment of childhood ITP. Methods This systematic review analyzed the overall platelet response, durability of treatment effect, and safety for RTX use in comparison to TPO‐RAs in pediatric ITP. MEDLINE/PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched through December 2020 and meta‐analysis was conducted using proportions of success/failure for each intervention in the selected studies. Results The proportion of participants achieving the primary endpoint of a platelet response above 50,000 was similar for TPO‐RAs (proportion = 0.71, 95% CI: 0.63–0.78) and RTX (proportion = 0.68, 95% CI: 0.53–0.82). However, considerable variation was found between the two groups with regards to the sustainability of the response and other secondary outcomes such as need for rescue and adverse events. RTX was associated with higher rates of rescue therapy. Conclusions In this analysis of prospective pediatric ITP studies, RTX and TPO‐RAs had similar rates of overall platelet response but differed in other important measures. Prospective comparative studies are needed to better characterize second‐line treatments for pediatric ITP.

A proposal for new definition (s) and management approach to paediatric refractory ITP: Reflections from the Intercontinental ITP Study Group

“…Because of all the above limitations at this time, we do not even have a clear understanding of the prevalence or incidence of this condition despite seeing rITP in clinical practice. An important caveat in rITP, particularly in paediatrics, includes a thorough investigation of underlying aetiology of the thrombocytopenia that often is not performed for typical ITP cases including evaluation for familial thrombocytopenia syndromes (even in the absence of family history) 15 and determination of immune function and screening for inborn errors of immunity 10 …”

“…For those children who require second-line therapy clinical trial data demonstrate response rates of >60% for the approved second-line therapies of eltrombopag 8 and romiplostim 9 and initial response rates of approximately 60% for rituximab. 10 Despite these high response rates, some children will have 'refractory' ITP (rITP) with poor or transient responses to platelet-raising therapies. A previous international working group defined patients, irrespective of age, as refractory if they met two key criteria: (1) they failed splenectomy and (2) they either continued to have severe ITP or a risk of bleeding requiring treatment.…”

“…Most children (>80% IVIG and >95% corticosteroids 5–7 ) will respond to first‐line therapies and are likely to enter spontaneous remission. For those children who require second‐line therapy clinical trial data demonstrate response rates of >60% for the approved second‐line therapies of eltrombopag 8 and romiplostim 9 and initial response rates of approximately 60% for rituximab 10 . Despite these high response rates, some children will have ‘refractory’ ITP (rITP) with poor or transient responses to platelet‐raising therapies.…”

Immune Thrombocytopenia in Children: What We Know, What We Need to Know

“…Ответ на ритуксимаб обычно наблюдается в течение 1-8 недель. У 50% пациентов ремиссия сохраняется более 2 лет [23].…”