Current Data on the Safety Profile of Baricitinib in the Treatment of Rheumatoid Arthritis

Baricitinib in the Treatment of RA

Baricitinib is an orally administered inhibitor of Janus kinases JAK1 and JAK2, approved for the treatment of moderate to severe RA in adult patients who have inadequately responded to or are intolerant of one or more disease-modifying antirheumatic drugs. Baricitinib can be used as monotherapy or in combination with methotrexate. 

Analysis Methodology and Evaluated Data

The long-term safety of baricitinib use in RA treatment was assessed based on 9 completed randomized studies (5 Phase III, 3 Phase II, 1 Phase 1b) and 1 ongoing long-term extension clinical study (LTE). The incidence rate of adverse events per 100 patient-years was calculated for all patients who received at least one dose of baricitinib. The incidence of deep vein thrombosis (DVT), pulmonary embolism (PE), and DVT and/or PE based on the dose of baricitinib was also determined. Serious cardiovascular events were evaluated in 5 Phase III studies and LTE.

Findings

Baricitinib was administered to 3770 patients with a median usage of 4.2 years and maximum exposure of 8.4 years (13,148 patient-years). The overall incidence rate of adverse events per 100 person-years was as follows:

• any adverse event during treatment: 25.8
• serious adverse event (including death): 7.2
• temporary treatment interruption due to adverse event: 9.5
• permanent discontinuation due to adverse event: 4.8
• death: 0.52
• serious infection: 2.7; opportunistic infection: 0.44; tuberculosis: 0.15; herpes zoster: 3.0
• serious cardiovascular event: 0.5
• DVT: 0.31; PE: 0.24; DVT/PE: 0.45
• malignancies other than non-melanoma skin cancers: 0.9; non-melanoma skin cancers: 0.33; lymphoma: 0.06
• GI perforation: 0.04

Results differed minimally between patients receiving 2 mg (n = 1077) or 4 mg (n = 3400) of baricitinib. The incidence of deaths tended to increase with the duration of follow-up (over 192 weeks), although no specific cause of death contributed to this increase. For all other safety parameters of interest, the incidence remained stable over 48-week treatment periods and was consistent with previous findings.

Conclusion

In the updated analysis of clinical trial data on baricitinib, used for moderate to severe rheumatoid arthritis, the safety profile of this medication was evaluated. Even with exposure up to 8.4 years, the occurrence of adverse events did not increase, and the safety profile remained consistent with earlier analyses.

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Sources:
1. Genovese M. C., Smolen J. S., Takeuchi T.et al. FRI0123 Safety profile of baricitinib for the treatment of rheumatoid arthritis up to 8.4 years: an updated integrated safety analysis. Ann Rheum Dis 2020; 79: 642−643.
2. SPC Olumiant. Available at: www.ema.europa.eu/en/documents/product-information/olumiant-epar-product-information_cs.pdf