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Risk of bleeding associated with BTK inhibitor monotherapy: a systematic review and meta-analysis of randomized
Dan Jiang1,2,3,4, Zaiwei Song1,2,3, Yang Hu1,2,3,4
1Department of Pharmacy, Peking University Third Hospital, Beijing, Haidian, China.
Background:
The bleeding risk associated with Bruton's tyrosine kinase inhibitor (BTKi) monotherapy remains to be understood. This systematic review aims to evaluate BTKi monotherapy related bleeding risk.
Research Design And Methods:
PubMed, Embase, and CENTRAL were searched up to 5 December 2021. We included randomized controlled trials (RCTs) comparing BTKi monotherapy with control drugs, or comparing different BTKi monotherapies.
Results:
10 studies with 3139 patients were included. Ibrutinib (vs. control drugs) significantly increased the risk of overall bleeding and major bleeding (RR = 2.22, 95% CI 1.80-2.75, P < 0.00001; RR = 1.80, 95% CI 1.02-3.18, P = 0.04, respectively). Acalabrutinib (vs. control drugs) had a significantly increased overall bleeding risk (RR = 3.45, 95% CI 2.39-4.99, p < 0.00001). A significant difference was found in overall bleeding between ibrutinib and acalabrutinib (RR = 1.35, 95% CI 1.11-1.64, P = 0.002). Compared to zanubrutinib, ibrutinib tended to increase the risk of major bleeding (RR = 1.55, 95% CI 0.57-4.18, P = 0.39).
Conclusions:
Ibrutinib and acalabrutinib (vs. control drugs) have a higher risk of bleeding and overall bleeding, respectively. Limited evidence suggests that ibrutinib (vs. acalabrutinib) significantly increases overall bleeding risk, but the differences are not observed in other comparisons.
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