JAK inhibitors vs traditional therapy for myelofibrosis; A meta-analysis of randomized clinical trials.

e18603 Background: Myelofibrosis (MF) is a type of myeloproliferative neoplasm. The pharmacological standard of care is the Janus kinase (JAK) inhibitor class (e.g., Ruxolitinib, Pacritinib, Momelotinib, Fedratinib), which targets key disease drivers. However, traditional therapies, often grouped as Best Available Therapy (BAT), including hydroxyurea and hematopoietic stem cell transplant, remain a significant comparator. A precise synthesis of data is needed to define the overall risk-benefit profile of JAK inhibitors versus these traditional treatments. This meta-analysis compares the efficacy (e.g., spleen volume reduction) and safety(e.g., hematological adverse events) of JAK inhibitors against traditional therapies for MF. Objective: To compare efficacy and safety of JAK inhibitors against traditional therapies in adult patients( age > 18 years ) with myelofibrosis. Methods: Following PRISMA guidelines, a systematic literature search of Randomized controlled trials(RCTs) was conducted in PubMed, Embase, and Clinical Trials Databases upto January 2026. We compared the efficacy and safety of JAK inhibitors to the traditional therapies often grouped as best available therapies including hydroxyurea, hematopoietic stem cell transplant and other measures in adult patients( age >18 years) diagnosed with Myleofibribrosis. Outcomes were splenic volume reduction and adverse hematological events such as Anemia and thrombocytopenia. Results: Eight RCTs involving 1917 patients with Myleofibrosis: 62% (1233) of patients were randomized to receive JAK inhibitors and 36% ( 682) participants were randomized to receive traditional therapies. This meta-analysis showed that the number of patients achieving spleen volume reduction ≥ 35 % at 24 weeks was significantly higher in JAKi compared to traditional therapies including placebo (RR: 6.11, 95% CI 3.56 to 10.49, I2= 0 %, with sensitive analysis by excluding two studies, while without sensitive analysis including two studies(RR:9.34, 95%CI 3.73 to 23.34, I2=77%) and the difference was statistically significant. Compared to traditional therapies, patients treated with JAKi showed higher adverse hematological adverse effects such as Anemia (OR: 1.55, 95%CI; 1.02 to 2.35, I2=56%) and thrombocytopenia (OR: 1.54 95% CI; 0.85 to 2.2.79, I2=84%). However, even though thrombocytopenia was observed, it was not found to be statistically significant. Conclusions: Overall, this meta analysis shows that JAK inhibitors have higher efficacy in reducing the splenic volume as compared to traditional therapies. However, JAK inhibitors are associated with more hematological side effects, specifically Anemia and thrombocytopenia. The limitations in the new trials should also be kept in mind while interpreting the results.