Introduction: Chronic immune thrombocytopenia (ITP) is characterized by low platelet counts, increasing the risk of bleeding. While first-line therapies are well-established, second-line treatments vary, including thrombopoietin receptor agonists, immune modulators, and emerging agents. Although some studies have compared second-line therapies, no comprehensive network meta-analysis (NMA) has evaluated the relative effectiveness of all available treatments, including eltrombopag, romiplostim, avatrombopag, fostamatinib, Syk inhibitors, and newer agents like rilzabrutinib. This study aims to address this gap, integrating real-world and clinical trial data to guide personalized treatment strategies.

Methods: A systematic search of five databases was conducted for relevant randomized controlled trials (RCTs). A network meta-analysis was performed using the Netmeta package in R, and visualizations were generated in Stata 18.0. The quality and risk of bias of included studies were assessed using the ROB 2.0 tool.

Results: From 396 records screened, 17 studies involving 3321 patients were included. The treatment groups were: Avatrombopag (96), Eltrombopag (283), Fostamatinib (101), Rilzabrutinib (133), Romiplostim (2116), and Rozanolixizumab (41). The overall survival odds ratios (OR) were as follows: Avatrombopag (OR 5.31, 95% CI [0.38; 75.18]), Eltrombopag (OR 2.23, 95% CI [0.35; 14.39]), Fostamatinib (OR 2.08, 95% CI [0.04; 105.90]), Rilzabrutinib (OR 3.47, 95% CI [0.07; 176.25]), Romiplostim (OR 3.23, 95% CI [0.59; 17.79]), and Rozanolixizumab (OR 0.67, 95% CI [0.04; 12.31]). SUCRA analysis ranked Rozanolixizumab as the most effective and Avatrombopag as the least effective. Time to reach >50 x 10^9/L was 19.5 ± 13 days, with an OR of 5.58 (95% CI [0.17; 179.25]). Platelet retention duration was 23.21 ± 15.5 days (OR 3.47, 95% CI [0.29; 41.56]). Safety outcomes showed risk ratios for adverse events: Rescue therapy (0.82 [95% CI: -1.18; 0.46]), Bleeding (-0.43 [95% CI: -0.92; 0.05]), Hepatic toxicity (0.02 [95% CI: 0.01; 0.04]), and Gastroenterological issues (0.51 [95% CI: 0.07; 0.96]). Quality of life, measured using the ITP-QOL, increased by 16 ± 13. Rituximab was analyzed indirectly and showed moderate efficacy. Risk of bias was low.

Conclusion: This NMA provides a comparative analysis of second-line therapies for chronic ITP, with Rozanolixizumab identified as the most effective treatment. Despite variability in safety profiles, all therapies demonstrated significant clinical benefits, supporting the adoption of personalized treatment strategies.

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