Long-Term Safety of Baricitinib for RA

ACR CONVERGENCE 2020—On May 31, 2018, the U.S. Food & Drug Administration (FDA) approved the oral, selective Janus kinase (JAK) 1/JAK 2 inhibitor, baricitinib, to treat adults with moderate to severe active rheumatoid arthritis for whom one or more tumor necrosis factor antagonists proved inadequate.¹

In November, an updated safety analysis was presented on the long-term use of baricitinib during ACR Convergence 2020. The study, from Winthrop et al., assessed safety using data from nine randomized clinical trials (phase 3: n=5; phase 2: n=3; phase 1b: n=1) and one long-term extension study.²

Data from all patients who received at least one dose of baricitinib through Sept. 1, 2019, were used to calculate an incidence rate per 100 patient-years of exposure, which was called the All-bari-RA analysis set. Incidence rates for deep vein thrombosis, pulmonary embolism, and deep vein thrombosis and/or pulmonary embolism were also calculated for patients in the All-bari-RA set who received 2 or 4 mg of baricitinib.

Major adverse cardiovascular events were adjudicated in the long-term extension study and the five phase 3 studies. The serious infections incidence rates were evaluated through week 24 in the phase 2 and 3 studies and the All-bari-RA analysis set. This analysis was stratified by age group: younger than 65 years and 65 years and older.

Within the All-bari-RA analysis set, events of interest were assessed over time in 48-month intervals. To account for the aging of patients, incidence rates for death and malignancy, excluding non-melanoma skin cancer, were standardized to the World Health Organization world population 2000–2025 within each time interval.

Results
Data were analyzed for baricitinib-treated patients (n=3,770) representing 13,148 patient-years of exposure, with a median of 4.2 years of exposure to a maximum of 8.4 years of exposure per patient. The overall incidence ratios per 100 patient-years of exposure were 25.8 for treatment emergent adverse events and 7.2 for serious adverse events, including death.

In the All-bari-RA analysis set, the incidence rates of serious infections for patients younger than 65 years old was 2.1 (95% confidence interval [CI], 1.9–2.4) and for those 65 years and older was 4.8 (95% CI, 4.0–5.7). For major adverse cardiovascular events, deep vein thrombosis, pulmonary embolism, deep vein thrombosis and/or pulmonary embolism, and non-melanoma skin cancer, the incidence rates remained generally stable. After adjusting for age, no increases in the rates of death or malignancies, excluding non-melanoma skin cancer, were found. The incidence rates across the safety profiles were consistent with previous analyses.