Efficacy and safety of rituximab for minors with immune thrombocytopenia: a systematic review and meta-analysis

Min Qu, Jing Zhou, Song-Jun Yang, Ze-Ping Zhou, Min Qu, Jing Zhou, Song-Jun Yang, Ze-Ping Zhou

Abstract

Objective: We reviewed relevant research on rituximab (RTX) treatment for pediatric immune thrombocytopenia (ITP) to elucidate the efficacy and safety of RTX.

Methods: Prospective clinical trials of RTX for the treatment of pediatric ITP were collected by searching the PubMed, Cochrane Library, Web of Science, and OVID: EMBASE databases and ClinicalTrials.gov. We examined rates of overall response (OR), complete response (CR), partial response (PR), sustained response (SR), relapse (R), and adverse drug reaction (ADR). The Methodological Index for Nonrandomized Studies scale was used, and sensitivity analyses were performed.

Results: For five studies, including 100 patients, the pooled OR, CR, PR, SR, R, and ADR rates were 52% (95% CI: 0.36-0.77, I2 = 78%), 52% (95% CI: 0.41-0.67, I2 = 45%), 18% (95% CI: 0.10-0.33, I2 = 33%), 43% (95% CI: 0.29-0.63, I2 = 0%), 25% (95% CI: 0.06-0.96, I2 = 52%), and 30% (95% CI: 0.15-0.58, I2 = 64%), respectively.

Conclusion: There is evidence, albeit low quality, that RTX may be a better second-line therapy than splenectomy for children with ITP; however, its efficacy and safety need to be validated by further high-quality clinical trials, such as randomized controlled trials.

Keywords: Methodological Index for Nonrandomized Studies; Rituximab; immune thrombocytopenia; meta-analysis; minor; splenectomy.

Conflict of interest statement

Declaration of conflicting interest: The authors declare that there is no conflict of interest.

Figures

Figure 1.
Figure 1.
PRISMA flowchart showing the study selection process for the systematic review. PRISMA, Preferred Reporting Items for Systematic reviews and Meta-Analyses.
Figure 2.
Figure 2.
Meta-analysis results of (a) overall response, (b) complete response, (c) partial response, (d) relapse, (e) sustained response, and (f) adverse drug reactions in the five papers evaluated: Wang et al. (2005), Bennett et al. (2006), Dogan et al. (2009), Citak and Citak (2011), and Ansari et al. (2014) 95% CI, 95% confidence interval.
Figure 3.
Figure 3.
Sensitivity analysis results of (a) overall response, (b) complete response, (c) partial response, (d) relapse, (e) sustained response, and (f) adverse drug reactions in the five papers evaluated: Wang et al. (2005), Bennett et al. (2006), Dogan et al. (2009), Citak and Citak (2011), and Ansari et al. (2014) 95% CI, 95% confidence interval.

References

    1. Heitink-Pollé KM, Nijsten J, Boonacker CW, et al. Clinical and laboratory predictors of chronic immune thrombocytopenia in children: a systematic review and meta-analysis. Blood 2014; 124: 3295–3307.
    1. Audia S, Mahévas M, Samson M, et al. Pathogenesis of immune thrombocytopenia. Autoimmun Rev 2017; 16: 620–632.
    1. Schmidt DE, Heitink-Polle KMJ, Laarhoven AG, et al. Transient and chronic childhood immune thrombocytopenia are distinctly affected by Fc-gamma receptor polymorphisms. Blood Adv 2019; 3: 2003–2012.
    1. Provan D, Arnold DM, Bussel JB, et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv 2019; 3: 3780–3817.
    1. Cines DB, Bussel JB, Liebman HA, et al. The ITP syndrome: pathogenic and clinical diversity. Blood 2009; 113: 6511–6521.
    1. Neunert C, Terrell DR, Arnold DM, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv 2019; 3: 3829–3866.
    1. Patel VL, Mahévas M, Lee SY, et al. Outcomes 5 years after response to rituximab therapy in children and adults with immune thrombocytopenia. Blood 2012; 119: 5989–5995.
    1. Liang Y, Zhang L, Gao J, et al. Rituximab for children with immune thrombocytopenia: a systematic review. PLoS One 2012; 7: e36698.
    1. Ansari S, Rostami T, Yousefian S, et al. Rituximab efficacy in the treatment of children with chronic immune thrombocytopenic purpura. Pediatr Hematol Oncol 2014; 31: 555–562.
    1. Slim K, Nini E, Forestier D, et al. Methodological index for non-randomized studies (minors): development and validation of a new instrument. ANZ J Surg 2003; 73: 712–716.
    1. Sterne JAC, Hernán MA, McAleenan A, et al. Chapter 25: Assessing risk of bias in a non-randomized study. In Cochrane Handbook for Systematic Reviews of Interventions version 6.1 (updated September 2020). Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane, 2020. Available from .
    1. Rodeghiero F, Stasi R, Gernsheimer T, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood 2009; 113: 2386–2393.
    1. Wang J, Wiley JM, Luddy R, et al. Chronic immune thrombocytopenic purpura in children: assessment of rituximab treatment. J Pediatr 2005; 146: 217–221.
    1. Bennett CM, Rogers ZR, Kinnamon DD, et al. Prospective phase 1/2 study of rituximab in childhood and adolescent chronic immune thrombocytopenic purpura. Blood 2006; 107: 2639–2642.
    1. Dogan M, Oner AF, Acikgoz M, et al. Treatment of chronic immune thrombocytopenic purpura with rituximab in children. Indian J Pediatr 2009; 76: 1141–1144.
    1. Citak EC, Citak FE. Treatment results of children with chronic immune thrombocytopenic purpura (ITP) treated with rituximab. J Trop Pediatr 2011; 57: 71–72.
    1. Parodi E, Rivetti E, Amendola G, et al. Long-term follow-up analysis after rituximab therapy in children with refractory symptomatic ITP: identification of factors predictive of a sustained response. Br J Haematol 2009; 144: 552–558.
    1. Dierickx D, Verhoef G, Van Hoof A, et al. Rituximab in auto-immune haemolytic anaemia and immune thrombocytopenic purpura: a Belgian retrospective multicentric study. J Intern Med 2009; 266: 484–491.
    1. Oved JH, Lee CSY, Bussel JB. Treatment of children with persistent and chronic idiopathic thrombocytopenic purpura: 4 infusions of rituximab and three 4-day cycles of dexamethasone. J Pediatr 2017; 191: 225–231.
    1. Dai WJ, Zhang RR, Yang XC, et al. Efficacy of standard dose rituximab for refractory idiopathic thrombocytopenic purpura in children. Eur Rev Med Pharmacol Sci 2015; 19: 2379–2383.
    1. Zaja F, Volpetti S, Chiozzotto M, et al. Long-term follow-up analysis after rituximab salvage therapy in adult patients with immune thrombocytopenia. Am J Hematol 2012; 87: 886–889.
    1. Tran H, Brighton T, Grigg A, et al. A multi-centre, single-arm, open-label study evaluating the safety and efficacy of fixed dose rituximab in patients with refractory, relapsed or chronic idiopathic thrombocytopenic purpura (R-ITP1000 study). Br J Haematol 2014; 167: 243–251.
    1. Grace RF, Bennett CM, Ritchey AK, et al. Response to steroids predicts response to rituximab in pediatric chronic immune thrombocytopenia. Pediatr Blood Cancer 2012; 58: 221–225.
    1. Mueller BU, Bennett CM, Feldman HA, et al. One year follow-up of children and adolescents with chronic immune thrombocytopenic purpura (ITP) treated with rituximab. Pediatr Blood Cancer 2009; 52: 259–262.
    1. Neunert C, Noroozi N, Norman G, et al. Severe bleeding events in adults and children with primary immune thrombocytopenia: a systematic review. J Thromb Haemost 2015; 13: 457–464.
    1. Labarque V, Van Geet C. Clinical practice: immune thrombocytopenia in paediatrics. Eur J Pediatr 2014; 173: 163–172.

Source: PubMed

3
S'abonner