Immune thrombocytopenia (ITP) is an autoimmune disorder, characterized by decrease of the platelet count and increased risk of bleeding. Although spleen tyrosine kinase (SYK) inhibitors have shown promise in treating ITP, no meta-analysis has yet synthesized the evidence from randomized controlled trials (RCTs) across the entire class. Therefore, there is no consolidated evaluation of the efficacy and safety of SYK inhibitors as a group, nor comparisons among different agents, limiting guidance for clinical practice and research.

This paper aims to synthesize the evidence from RCTs for SYK inhibitors in adults with chronic ITP and to compare the effects of different agents, conditional on the availability of data.

Eligible studies were phase III RCTs comparing SYK inhibitors to placebo in ITP patients and reporting at least one relevant clinical outcome. Studies with overlapping populations, duplicate reports, or secondary ITP were excluded. Data were extracted from published reports on PubMed, Embase, and Cochrane. Risk Ratios (RR) with 95% Confidence Interval (95% CI) were pooled across trials. The primary efficacy outcome was the stable response rate (defined as ≥ 4 platelet count ≥ 50×10⁹/L in 14-24 weeks). Secondary efficacy endpoints included other platelet count improvements and the need for rescue therapy. Safety outcomes comprised any Adverse Events (AEs) and other AEs.

Four trials (n = 372) were included. Syk inhibitors were given to 249 patients (66.9%): 123 (49.3%) received Fostamatinib and 126 (50.6%) Sovlepenib. SYK inhibitors significantly increased stable and overall platelet responses compared to placebo (RR = 17.77; 95% CI 5.13‒61.61; p < 0.00001 and RR 4.17; 95% CI 2.63‒6.61; p < 0000.1). Among individuals presenting with more pronounced thrombocytopenia at baseline (< 15×10⁹/L), SYK inhibitors were favored in the increase of platelet count of ≥ 30 × 10⁹/L and ≥ 20×10⁹/L from baseline at weeks 12 and 24 (RR = 3.53; 95% CI 1.96– 6.37; p < 0.0001, and RR = 3.67; 95% CI 2.00–6.71; p < 0.001). SYK inhibitor use reduced rescue treatment need but increased AEs, particularly hypertension, while severe AEs were not significantly different. Subgroup analyses comparing different SYK inhibitors were exploratory, due to the low number of studies involved, and none of the outcomes demonstrated a statistically significant difference between subgroups.

The present study is the first systematic review with meta-analysis to specifically evaluate the class of SYK inhibitors for the treatment of chronic ITP based solely on data from RCTs. Compared to the previous meta-analysis restricted to fostamatinib, in their subgroup analysis of RCTs, our findings suggest a stronger treatment effect for SYK inhibitors overall, particularly for stable response (RR 17.77 vs. 6.43) and overall response (RR 4.17 vs. 3.04), while the direction of benefit remained consistent across studies. In conclusion, this study provides evidence supporting SYK inhibitors as viable options in the treatment of chronic ITP. Given the small number of contributing studies, these results should be interpreted cautiously. Large-scale multicenter RCTs are needed to assess the safety and effectiveness of different SYK inhibitors in order to guide clinical decisions and optimize ITP management.