SAFETY PROFILE OF BARICITINIB FOR THE TREATMENT OF RHEUMATOID ARTHRITIS UP TO 8.4 YEARS: AN UPDATED INTEGRATED SAFETY ANALYSIS
Objectives:
Baricitinib (bari) is an oral selective inhibitor of Janus kinase (JAK) 1 and 2, approved for the treatment of moderately to severely active rheumatoid arthritis (RA) in adults. Here we update the drug’s safety profile with data up to 8.4 years of treatment.
Introduction:
Baricitinib (bari) is an oral selective inhibitor of Janus kinase (JAK) 1 and 2, approved for the treatment of moderately to severely active rheumatoid arthritis (RA) in adults. Here we update the drug’s safety profile with data up to 8.4 years of treatment.
Methods:
Long-term safety of bari was assessed from 9 completed randomized trials (5 Ph3, 3 Ph2, 1 Ph 1b) and 1 ongoing long-term extension (LTE) study. Incidence rates (IR) per 100 patient-years (PY) were calculated for all patients with RA treated with ≥1 dose of bari through 1-Sep-2019 (All-Bari-RA analysis set). IRs for deep vein thrombosis (DVT), pulmonary embolism (PE), and DVT and/or PE (DVT/PE) were also calculated for groups of patients while receiving bari 2mg or bari 4mg within All-Bari-RA. Major adverse cardiovascular events (MACE) were adjudicated in 5 phase 3 studies and the LTE.
Results:
3770 pts received bari for 13,148 PY, with a median and maximum exposure of 4.2 and 8.4 years, respectively. Overall IRs per 100 PY were: for any treatment-emergent adverse event (AE)(25.8); serious AE (including death)(7.2); temporary interruption due to AE (9.5); permanent discontinuation due to AE (4.8); death (0.52); serious infection (2.7); opportunistic infection (0.44) (excluding tuberculosis [TB], including multidermatomal herpes zoster [HZ]); TB (0.15); HZ (3.0); MACE (0.50); DVT (0.31); PE (0.24); DVT/PE (0.45); malignancies excluding non-melanoma skin cancer (NMSC) (0.90); NMSC (0.33); lymphoma (0.07); and gastrointestinal perforation (0.04). Incidence rates (IR)[95% confidence intervals] for patients while receiving bari 2mg (N=1077) and bari 4mg (N=3400) were DVT 2mg (0.38) [0.18, 0.73] and 4mg (0.30) [0.21, 0.43]; PE 2mg (0.26) [0.09, 0.56] and 4mg (0.25) [0.16, 0.36]; and DVT/PE 2mg (0.47) [0.23, 0.84] and 4mg (0.46) [0.34, 0.61]. IRs for death tended to increase in later time intervals (beyond 192 weeks). No particular cause of death contributed to this increase. For all other safety topics of interest, across 48-week treatment intervals, IRs remained stable over time (Figure). Across safety topics, IRs were consistent with previous analyses1,2.
Discussion:
In this update with 3,021 additional PY of exposure, bari maintained a safety profile similar to that previously reported,1,2 with no increase of IRs across safety topics through exposures up to 8.4 years.