EJHaem · 2026
Comparative Efficacy and Safety of Bruton Tyrosine Kinase and Spleen Tyrosine Kinase Inhibitors in Immune Thrombocytopenia: A Network Meta-Analysis of Clinical Trials.
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Abulehia Ayah, Alshareef Raneen Bilal, Khateeb Shorouq, Ghanem Usra, Abadi Amir, Zatar Nora, Bael Peter, Sweity Raghad, Ghanem Hamid, Ayesh Hazem
Аннотация
INTRODUCTION: Targeted kinase inhibitors have shown statistically and clinically significant improvements in platelet response among patients with primary ITP, supporting their utility as effective targeted therapeutic strategies. We evaluated the efficacy and safety of Bruton tyrosine kinase (BTK) and spleen tyrosine kinase (SYK) inhibitors in primary immune thrombocytopenia (ITP) using network meta-analysis.
METHODS: Following PRISMA-NMA guidelines, five trials, including 660 patients, were analyzed. Comparing rilzabrutinib, HMPL-523 (sovleplenib), and fostamatinib against placebo. The primary outcome was platelet response (≥ 50 × 109/L), while secondary outcomes included adverse events and treatment discontinuation. Risk ratios (RRs) with 95% confidence intervals (CIs) were estimated using a frequentist random-effects model.
RESULTS: All treatments significantly improved platelet response versus placebo. Sovleplenib 300 mg showed the greatest efficacy (RR = 30.51, 95% CI: 4.33-214.90), followed by rilzabrutinib 400 mg (RR = 16.60, 95% CI: 2.32-118.92), and fostamatinib 100 mg (RR = 6.51, 95% CI: 1.62-26.08). No significant differences were observed in overall adverse events. Treatment discontinuation risk was lowest with fostamatinib (RR = 1.10, 95% CI: 0.29-4.27).
CONCLUSION: Targeted kinase inhibitors demonstrated clinically meaningful improvements in platelet response in primary ITP, supporting their role as effective targeted therapeutic options. Comparative safety profiles varied, and no clear class-level superiority was established. Therefore, further large head-to-head trials with standardized outcome definitions and longer follow-up durations are needed to confirm long-term efficacy, safety, and consistency of treatment effects across clinical outcomes.
TRIAL REGISTRATION: The authors have confirmed clinical trial registration is not needed for this submission.
METHODS: Following PRISMA-NMA guidelines, five trials, including 660 patients, were analyzed. Comparing rilzabrutinib, HMPL-523 (sovleplenib), and fostamatinib against placebo. The primary outcome was platelet response (≥ 50 × 109/L), while secondary outcomes included adverse events and treatment discontinuation. Risk ratios (RRs) with 95% confidence intervals (CIs) were estimated using a frequentist random-effects model.
RESULTS: All treatments significantly improved platelet response versus placebo. Sovleplenib 300 mg showed the greatest efficacy (RR = 30.51, 95% CI: 4.33-214.90), followed by rilzabrutinib 400 mg (RR = 16.60, 95% CI: 2.32-118.92), and fostamatinib 100 mg (RR = 6.51, 95% CI: 1.62-26.08). No significant differences were observed in overall adverse events. Treatment discontinuation risk was lowest with fostamatinib (RR = 1.10, 95% CI: 0.29-4.27).
CONCLUSION: Targeted kinase inhibitors demonstrated clinically meaningful improvements in platelet response in primary ITP, supporting their role as effective targeted therapeutic options. Comparative safety profiles varied, and no clear class-level superiority was established. Therefore, further large head-to-head trials with standardized outcome definitions and longer follow-up durations are needed to confirm long-term efficacy, safety, and consistency of treatment effects across clinical outcomes.
TRIAL REGISTRATION: The authors have confirmed clinical trial registration is not needed for this submission.