Safety and efficacy of romiplostim in children and adolescents with Immune thrombocytopenia: A systematic review

Oliveira, Fernanda Lubiana de; Sequeira, Fernanda Silva; Garanito, Marlene Pereira

doi:10.1016/j.htct.2022.09.1275

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Hematology, Transfusion and Cell Therapy

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Sumário

Review article • Hematol., Transfus. Cell Ther. 45 (1) • Jan-Mar 2023 • https://doi.org/10.1016/j.htct.2022.09.1275 copy

Safety and efficacy of romiplostim in children and adolescents with Immune thrombocytopenia: A systematic review

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective

To evaluate the efficacy and safety of romiplostim (thrombopoietin-receptor agonist) in the treatment of pediatric immune thrombocytopenia (ITP).

Methods

Searches were conducted in MEDLINE, EMBASE, LILACS, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov (from January 2011 to August 2021). Randomized controlled trials (RCTs), double-blind, comparing romiplostim with a placebo in pediatric persistent or chronic ITP were included. The primary outcome was the overall response rate (platelets ≥ 50 × 10⁹/L) in the absence of rescue therapy for at least two consecutive weeks. The secondary endpoints were the minimization of clinically significant bleeding and the necessity for rescue treatments and the maximization of safety (incidence of overall adverse events) and durable response (maintaining platelet counts for at least twelve weeks).

Results

Two double-blind randomized placebo-controlled trials (84 participants) were included in this systematic review. Our data showed that, compared to the placebo group, the proportion of patients achieving durable platelet response was significantly higher in the romiplostim group (p= 0.003, RR = 6.34, 95%CI = 1.89 - 21.23), as was the overall response in the romiplostim group (p= 0.002, RR = 3.62, 95%CI = 1.63 - 8.03). Significant bleeding incidents (p= 0.49), overall adverse events (p= 0.71) and the need for rescue treatment (p= 0.13) were not statistically different between the romiplostim and placebo groups.

Conclusions

Romiplostim might improve both durable and overall platelet response in children and adolescents with ITP, compared to a placebo. More clinical trials are needed to evaluate the efficacy and safety of romiplostim and to compare it with other second-line treatments that are being used in pediatric ITP.

Keywords
Purpura; Thrombocytopenic; Idiopathic; Romiplostim; Pediatrics

	MEDLINE	EMBASE	Cochrane	LILACS	Clinical Trials.gov
Descriptors	MeSH	Emtree	MeSH	DeCS
English	“purpura, thrombocytopenic,	“idiopathic thrombocytopenic	“purpura, thrombocytopenic,	“idiopathic thrombocytopenic	“purpura, thrombocytopenic”
	idiopathic and romiplostim”	purpura and romiplostim”	idiopathic and romiplostim”	purpura and romiplostim”	“romiplostim”
Spanish				“púrpura trombocitopénica
				idiopática y romiplostim”
Portuguese				“purpura trombocitopenica
				idiopatica e romiplostim”
Filters	Clinical Trial	Controlled clinical trial	Clinical Trials	No	Interventional studies
	Randomized Controlled Trial	Randomized controlled trial	From 2011/1/1 to 2021/8/23	From 2011/1/1 to 2021/8/23	Studies with results
	Child: birth-18 years	infant OR child			Child (birth - 17)
	From 2011/1/1 to 2021/8/23	OR preschool			From 2011/1/1 to 2021/8/23
		OR school
		OR adolescent
		From 2011/1/1 to 2021/8/23

Characteristic/ Study ID	Bussel, 2011¹¹11 Bussel JB, Buchanan GR, Nugent DJ, Gnarra DJ, Bomgaars LR, Blanchette VS, et al. A randomized, double-blind study of romiplostim to determine its safety and efficacy in children with immune thrombocytopenia. Blood. 2011;118(1):28-36.	Tarantino, 2016¹²12 Tarantino MD, Bussel JB, Blanchette VS, Despotovic J, Bennett C, Raj A, et al. Romiplostim in children with immune thrombocytopenia: a phase 3, randomised, double-blind, placebo-controlled study. Lancet. 2016;388(10039):45-54.
Participants, N	22	62
Sex (male %)	73.0	43.5
Ethnicity (Caucasian %)	59.0	66.0
Previous splenectomy (%)	36.0	3.0
≥ 3 Previous ITP drug treatments (%)	86.5	21

Study	Starting dose	Dose adjustment	Follow-up during double-blind phase
Bussel, 2011	1 μg/kg, once weekly	Dose increased by 2 μg g/kg after 2 consecutive weeks of PLT < 50 × 10⁹/L;	12 weeks
		Dose remained constant when PLT 50 - 250 × 10⁹/L
		Dose reduced by 1 μg/kg after 2 consecutive weeks of PLT 250 - 400 × 10⁹/L
		Next scheduled dose held and the dose was reduced by 1 μg/kg
		on the next scheduled dosing day if PLT < 250 × 10⁹/L
Tarantino, 2016	1 μg/kg, once weekly	1 - 10 μg/kg (maximum dose) to target platelet counts of 50 - 200 × 10⁹/L	24 weeks
		Dose reduced by 1 μg/kg after 2 consecutive weeks of PLT 200 - 400 × 10⁹/L
		If 400×109/L, dosing was withheld until platelets < 200×10⁹/L

Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH) R. Dr. Diogo de Faria, 775 cj 133, 04037-002, São Paulo / SP - Brasil - São Paulo - SP - Brazil
E-mail: htct@abhh.org.br

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[1] ⁎ Corresponding author at: Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFM-USP), Rua Galeno de Almeida, 148, Pinheiros, São Paulo, SP CEP: 05410-030, Brazil. E-mail address: nandalubiana@gmail.com (F.L. de Oliveira)