Introduction: Sickle cell disease (SCD) is a debilitating hemoglobinopathy characterized by recurrent vaso-occlusive crises (VOCs), which significantly impair quality of life and lead to increased morbidity and mortality. These crises are primarily mediated by P-selectin–induced adhesion of blood cells to the endothelium. Crizanlizumab, a monoclonal antibody targeting P-selectin, has emerged as a potential therapeutic agent to reduce the frequency of VOCs. This systematic review and meta-analysis evaluates the efficacy and safety of crizanlizumab in patients with SCD by analysing evidence from randomized controlled trials and observational studies.

Methods: This systematic review and meta-analysis were conducted following the PRISMA guidelines. Through June 2025, a comprehensive literature search of PubMed, Embase, Web of Science, and the Cochrane Library was conducted. Eligible studies included randomized controlled trials and observational studies comparing crizanlizumab with placebo or standard therapy. The primary outcome was the annual rate of VOCs. Secondary outcomes included time to first VOC, opioid use, adverse events (AEs), serious adverse events (SAEs), and all-cause mortality. Pooled effect sizes were calculated using a random-effects model. Risk ratios (RRs) were used for dichotomous outcomes, and hazard ratios (HRs) for time-to-event outcomes, both with corresponding 95% confidence intervals (95% CIs). Statistical significance was set at p < 0.05. Heterogeneity was assessed using the I² statistic.

Results: A total of two studies comprising 299 patients receiving crizanlizumab and 317 patients receiving placebo were included. Crizanlizumab did not significantly reduce the frequency of VOCs compared to placebo (RR = 0.97, 95% CI: 0.90–1.06, p = 0.51, I² = 0%). The risk of adverse events was higher in the crizanlizumab group, but the difference was not statistically significant (RR = 1.20, 95% CI: 0.85–1.69, p = 0.31, I² = 6%). No significant difference was observed in SAEs (RR = 0.99, 95% CI: 0.29–3.36, p = 0.98, I² = 0%). Mortality data were not pooled due to inadequate reporting.

Conclusion: While crizanlizumab targets a key mechanism underlying VOCs in sickle cell disease, current evidence does not demonstrate a statistically significant benefit in reducing VOCs, adverse events, or serious adverse events compared to placebo. The low heterogeneity across studies suggests consistency in findings, but further large-scale clinical trials are warranted to clarify its clinical utility and identify potential subgroups that may benefit.

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2025
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