Evolving Therapeutic Approaches and Unmet Needs Leading to JAK Inhibitors in Myelofibrosis

Before JAK inhibitors became the cornerstone of myelofibrosis treatment, clinicians relied on conventional therapies such as hydroxyurea for cytoreduction, corticosteroids for symptom relief, and erythropoiesis-stimulating agents or androgens to address anemia. While these approaches offered modest benefits, they were limited in their ability to target the underlying disease biology. Some still play a role today—particularly in managing cytopenias or specific symptom profiles—but their impact remains largely supportive. The significant unmet need for treatments that could reduce splenomegaly, alleviate systemic symptoms, and modify the inflammatory drivers of disease spurred the development of JAK inhibitors. These therapies provided the first mechanism-based approach, offering more consistent symptom improvement and disease control. Their emergence marked a major advancement in addressing both the biologic and clinical burden of myelofibrosis.