Background/Purpose: Baricitinib (bari) is an oral selective Janus kinase (JAK)1/JAK 2 inhibitor approved for the treatment of moderately to severely active rheumatoid arthritis (RA) in adults. The objective of this study was to update bari’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 Phase 3, 3 Phase 2, 1 Phase 1b) and one ongoing long-term extension (LTE) study. Incidence rates (IR) per 100 patient-years of exposure (PYE) were calculated for all patients 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. IRs for serious infections were evaluated by age group (< 65 vs. ≥65) through Week 24 for patients randomized to placebo and bari 4 mg in 7 Phase 2/3 trials (Bari-RA-PC analysis set) as well as within All-BARI-RA. Within All-Bari-RA, events of interest were assessed over time in 48-month intervals. In addition, to account for aging of the cohort, IRs for death and malignancy (excluding non-melanoma skin cancer [NMSC]) were directly standardized to the WHO world population 2000-2025 within each time interval.

Results: A total of 3770 patients received bari for 13,148 PYE, with a median and maximum exposure of 4.2 and 8.4 years, respectively. Overall IRs per 100 PYE for any treatment-emergent adverse event (AE) and serious AE (including death) were 25.8 and 7.2, respectively (Table). Within All Bari-RA, IRs (95% confidence intervals [CI]) for patients while receiving bari 2mg (N=1077) or bari 4mg (N=3400), respectively, were 0.4 (0.2, 0.7) and 0.3 (0.2, 0.4) for DVT, 0.3 (0.1, 0.6) and 0.3 (0.2, 0.4) for PE, and 0.5 (0.2, 0.8) and 0.5 (0.3, 0.6) for DVT/PE. In All-Bari-RA, IRs (95% CI) of serious infections for patients age < 65 and ≥65 were 2.1 (1.9, 2.4) and 4.8 (4.0, 5.7), respectively. In Bari-RA-PC, IRs (95% CI) of serious infections for placebo (N=1215) and bari 4mg (N=1142) treatment groups, respectively, were 3.1 (1.6, 5.4) and 3.3 (1.8, 5.6) among patients < 65 and 9.9 (4.0, 20.4) and 7.0 (2.6, 15.2) among those ≥65. For MACE, DVT/PE, and NMSC, IRs generally remained stable over time (Figure). There were no increases in rates of death or non-NMSC malignancy after adjustment for aging of the cohort. Across safety topics, IRs were consistent with previous analyses^1,2. 

Conclusion: In this update with 13,148 PYE, 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.           

References:

1. Smolen JS et al. J Rheumatol. 2019 Jan;46(1):7-18
2. Genovese MC et al. Ann Rheum Dis. 2019 78(supp. 2):A308

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/safety-profile-of-baricitinib-for-the-treatment-of-rheumatoid-arthritis-up-to-8-4-years-an-updated-integrated-safety-analysis/