Infections in baricitinib clinical trials for patients with active rheumatoid arthritis. Annals of the rheumatic diseases Winthrop, K. L., Harigai, M., Genovese, M. C., Lindsey, S., Takeuchi, T., Fleischmann, R., Bradley, J. D., Byers, N. L., Hyslop, D. L., Issa, M., Nishikawa, A., Rooney, T. P., Witt, S., Dickson, C. L., Smolen, J. S., Dougados, M. 2020


OBJECTIVES: To evaluate the incidence of infection in patients with active rheumatoid arthritis (RA) treated with baricitinib, an oral selective Janus kinase (JAK)1 and JAK2 inhibitor.METHODS: Infections are summarised from an integrated database (8 phase 3/2/1b clinical trials and 1 long-term extension (LTE)) with data to 1 April 2017. The 'all-bari-RA' analysis set included patients who received any baricitinib dose. Placebo comparison was based on six studies with 4mg and placebo to week 24, including four trials with 2mg (placebo-controlled set). Dose-response assessment was based on four studies with 2mg and 4mg, including LTE data (2-4 mg extended set).RESULTS: There were 3492 patients who received baricitinib for 7860 patient-years (PY) of exposure (median 2.6 years, maximum 6.1 years). Treatment-emergent infections were higher for baricitinib versus placebo (exposure-adjusted incidence rate (IR)/100 PY: placebo 75.9, 2mg 84.0 (p not significant), 4mg 88.4 (p=0.001)). The IR of serious infection was similar for baricitinib versus placebo and stable over time (all-bari-RA IR 3.0/100 PY). There were 11 cases of tuberculosis (all-bari-RA IR 0.1/100 PY); all occurred with 4mg in endemic regions. Herpes zoster (HZ) IR/100 PY was higher for baricitinib versus placebo (placebo 1.0, 2mg 3.1 (p not significant), 4mg 4.3 (p=0.01)); rates remained elevated and stable over time (all-bari-RA 3.3). Opportunistic infections, including multidermatomal HZ, were infrequent in the baricitinib programme (all-bari-RA IR 0.5/100 PY).CONCLUSIONS: Increased rates of treatment-emergent infections including HZ were observed in patients with RA treated with baricitinib, consistent with baricitinib's immunomodulatory mode of action.

View details for DOI 10.1136/annrheumdis-2019-216852

View details for PubMedID 32788396