INTRODUCTION
myeloproliferative neoplasm, anemia, splenomegaly, Myeloproliferative Neoplasm, Myelofibrosis
DISEASE, ANEMIA, MYELOPROLIFERATIVE NEOPLASM, BONE MARROW FIBROSIS, MYELOPROLIFERATIVE NEOPLASM, TSS, MYELOFIBROSIS
Myelofibrosis (MF) is a rare myeloproliferative neoplasm characterized by bone marrow fibrosis, constitutional symptoms, anemia, and splenomegaly with an annual incidence of 0.5–1.5 cases per 100,000 individuals in the United States.The manifestation of MF symptoms is heterogeneous because some patients may experience none, some, or all common MF symptoms in differing degrees of severity. Approved JAK inhibitors (i.e., ruxolitinib, fedratinib) are currently recommended as standard of care,Momelotinib is a potent, selective, orally bioavailable inhibitor of JAK1, JAK2, and activin A receptor type 1 (ACVR1), also known as activin receptor‐like kinase‐2, with a differentiated therapeutic profile in MF, which was examined in the phase III SIMPLIFY trials.Phase III trials evaluating JAK inhibitors in MF have historically defined symptom response as achieving at least a 50% reduction in TSS, measured by the modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN‐SAF) at the end of a 24‐week treatment period compared with baseline.Analyses beyond the dichotomous “responder” or “non‐responder” method of evaluating symptom response may further depict the true impact of the disease and treatment effects on patient experiences. A continuous endpoint, such as mean change from baseline as assessed by a mixed‐effect model for repeated measures (MMRM) analysis, has greater statistical power and quantifies the degree of benefit experienced by each patient and may be more discriminatory than the dichotomous response analysis, which defines non‐responders as those with an improvement of less than 50% or achieving no meaningful benefit.Daily digital collection of patient‐reported outcome (PRO) data allows for longitudinal benefit assessment throughout the duration of the trial rather than landmark data that use scores only from Week 21 through Week 24 for response rate. Furthermore, individual items of the MPN‐SAF are scored collectively to reflect a construct and, therefore, detailed insights into the driving factors that influence treatment‐related changes are lost. For example, some items may have greater clinical importance than others or may be more sensitive to treatment effects.Here, we report longitudinal change from baseline of MF domain‐level symptoms using a continuous endpoint based on the MMRM methodology with accompanying individual item‐level analyses to support the interpretation of symptom benefit experienced by patients with MF in each of the 2 SIMPLIFY trials.