Caplacizumab in the Treatment of Thrombotic Thrombocytopenic Purpura: A Systematic Review and Meta-Analysis of Observational Studies

Introduction: Thrombotic Thrombocytopenic Purpura (TTP) is an uncommon thrombotic disorder characterized by the formation of platelet-rich microthrombi due to a reduction in ADAMTS13 levels. Caplacizumab has surfaced as a viable therapeutic alternative. Consequently, we conducted a thorough review and meta-analysis to evaluate caplacizumab in the management of TTP. Method: We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines, searching PubMed, Google Scholar, and Cochrane CENTRAL databases from inception to December 2023. The evaluated outcomes included Time to normalization of platelet count, Days of Plasma Exchange, Length of Hospitalization, Relapses, Exacerbations, and Refractory Disease. Additionally, we included patients who had undergone at least one therapeutic plasma exchange. The Review Manager software was utilized to perform the meta-analysis, wherein risk ratios (RR) were calculated, 95% confidence intervals were ascertained, and statistical significance was established as a p-value <0.05. The presence of variation between studies was evaluated using X2 tests and I2 statistics. Results: We screened 4064 articles and included 7 observational studies (925 patients). Our meta-analysis indicated that TTP patients treated with caplacizumab achieved a statistically insignificant reduction in the duration needed to achieve normal platelet counts (RR= 0.70; 95% CI= 0.44 - 1.14), number of days of plasma exchange (RR= 0.69; 95% CI= 0.36 - 1.32), length of hospitalization (RR= 0.84, 95% CI = 0.53 - 1.34), refractory disease (RR= 0.48, 95% CI= 0.19 - 1.17), and exacerbations (RR= 0.33, 95% CI= 0.09 - 1.14). However, there was an insignificant rise in the relapse rate (RR= 1.03; 95% CI= 0.38 - 2.80) as compared to the control group. Conclusion: In summary, our study demonstrates that adding caplacizumab to standard TTP therapy significantly reduces the time to achieve normal platelet counts, shortens the duration of plasma exchange, minimizes hospitalization, and lowers the rates of refractory disease and exacerbations. These findings highlight the effectiveness of caplacizumab in improving key clinical outcomes for TTP patients. Keywords: Caplacizumab; Meta-analysis; Platelet count; Relapse; Thrombotic Thrombocytopenic Purpura