Crizanlizumab and comparators for adults with sickle-cell disease: a systematic review and network meta-analysis

H Z Thom*, H-Y Cheng, et al.

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

Objectives Treatment options for preventing vaso-occlusive crises (VOC) among patients with sickle cell disease (SCD) are limited, especially if hydroxyurea treatment has failed or is contraindicated. A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the efficacy and safety of crizanlizumab for older adolescent and adult (≥16 years old) SCD patients. Methods The SLR included randomised controlled trials (RCTs) and uncontrolled studies. Bayesian NMA of VOC, all-cause hospitalisation days and adverse events were conducted. Results The SLR identified 51 studies and 9 RCTs on 14 treatments that met the NMA inclusion criteria. The NMA found that crizanlizumab 5.0 mg/kg was associated with a reduction in VOC (HR 0.55, 95% credible interval (0.43, 0.69); Bayesian probability of superiority >0.99), all-cause hospitalisation days (0.58 (0.50, 0.68); >0.99) and no evidence of difference on adverse events (0.91 (0.59, 1.43) 0.66) or serious adverse events (0.93 (0.47, 1.87); 0.59) compared with placebo. The HR for reduction in VOC for crizanlizumab relative to L-glutamine was (0.67 (0.50, 0.88); >0.99). These results were sensitive to assumptions regarding whether patient age is an effect modifier. Conclusions This NMA provides preliminary evidence comparing the efficacy of crizanlizumab with other treatments for VOC prevention.
Original languageEnglish
Article numbere034147
Number of pages11
JournalBMJ Open
Volume10
Issue number9
DOIs
Publication statusPublished - 17 Sep 2020

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