PF679 REAL‐WORLD SAFETY DATA FROM A NONINTERVENTIONAL LONG‐TERM POSTAUTHORIZATION SAFETY STUDY OF RUXOLITINIB IN MYELOFIBROSIS
Authors: Barraco F. , Greil R. , Herbrecht R. , Schmidt H. Burkhard , Reiter A. , Willenbacher W. , Raymakers R. , Liersch R. , Wroclawska M. , Pack R. , Burock K. , Levine M. , Gisslinger H. 
Published: June 2019

Background:Ruxolitinib (RUX, oral JAK inhibitor) was approved for treatment (Tx) of patients (pts) with myelofibrosis (MF) based on the data from COMFORT I/II (phase 3 registrational studies). At the time of submission of the Marketing Authorization Application in the European Union (EU), a significant number of pts (589) had been exposed to RUX in clinical studies. However, there was a lack of postmarketing exposure data leading to an agreement with the European Medicines Agency to conduct this postauthorization safety study (PASS [ENCePP No. 3296]: per EU Vol. 9a [Rules for Medicinal Products]).Aims:To provide real‐world safety data on pts with MF exposed/nonexposed to RUX.Methods:This was a prospective, multicenter, noninterventional PASS study for adult pts with MF (primary [per WHO criteria]/secondary [per IWG‐MRT criteria]). The primary objective was to study long‐term safety (incidence of adverse drug reactions [ADRs]/serious adverse events [SAEs]) in pts with MF treated with RUX as per prescribing information. The key secondary objectives included the incidence/outcome of events of special interest (EoSI [bleeding events, serious/opportunistic infections, second primary malignancies, and deaths]). The statistical analysis was done after last pt completed 3 years on the study or discontinued early (final database lock, July 5, 2018).Results:Overall, 462 pts were included (prevalent users = 260, new users = 32, nonexposed = 170 [inclusive of RUX‐switch {N = 57}]). The demographic/baseline pt characteristics (representative of pts with MF and well balanced across all types of users) and pt disposition will be described in the presentation. The study duration, RUX‐exposure, summary of dose reductions/interruptions (primary reasons: medical decisions/ADRs across all cohorts), Tx‐emergent ADRs, and Tx‐emergent SAEs are summarized in Table A. The exposure‐adjusted incidence rates of ADRs and SAEs were comparable among the new users’ vs the prevalent users’ cohorts (ADR: 19.3 vs 19.6; SAE: 25.2 vs 25.0; Table A). The most frequently reported ADRs across all types of cohorts included thrombocytopenia, anemia, epistaxis, and herpes zoster. The incidence rates of thrombocytopenia and anemia were higher in the RUX‐switch vs prevalent users’/new users’ cohorts (shorter duration of exposure in the RUX‐switch cohort). Anemia, pneumonia, and general physical health deterioration were the most frequently reported SAEs across all cohorts. The incidence rate of Tx‐emergent SAE (any SAE) was slightly higher in RUX‐switch cohort vs the prevalent users’/new users’ cohorts. The Tx‐emergent EoSIs are presented in Table B. Bleeding events were reported in a larger proportion of pts in the prevalent users’ cohort; while serious/opportunistic infections were reported in a larger proportion of pts in the new users’ cohort (vs other cohorts). The second primary malignancies were reported in a larger proportion of pts in the prevalent users’ cohort (Table B). The incidence rate of on‐Tx deaths (due to any cause [mostly attributed to progression of underlying MF, sepsis, and pneumonia]) is listed in Table B.Summary/Conclusion:The long‐term safety of RUX as assessed in this real‐world PASS study was consistent with the previous findings (COMFORT I/II). Of note, the study comprised of a broader population including pts at lower risk/elderly pts vs the COMFORT I/II study populations. No new or unexpected safety signals were identified with the long‐term Tx. Overall, the observed safety profile of RUX in this PASS study along with the safety findings from COMFORT I/II support the long‐term Tx with RUX in pts with MF.image