Cross-Study Comparisons of JAK2 Inhibitors in Myelofibrosis: Risks and Recommendations

With multiple Janus Kinase (JAK) inhibitors approved or in late development for myelofibrosis, there is a logical desire in the field for comparative efficacy and safety data among these agents in order to inform treatment selection. However, due to the highly disparate nature of patient populations enrolled in different JAK inhibitor trials, as well as key differences in study design, any cross-study comparative analyses should be undertaken with a high degree of caution. Here, we show how differences in enrolled populations can impact both efficacy and safety conclusions and why quantitative comparisons of outcomes across studies is prone to spurious conclusions. We conclude by offering guidance on how to approach comparative analyses in the absence of direct head-to-head data based on a thorough understanding of how study design impacts outcomes. Ultimately there is enough room in the myelofibrosis treatment landscape for multiple JAK inhibitors, and sequencing of therapies should depend on how each agent was studied and where it showed the most benefit, both in trials and in real-world practice.