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Infections in baricitinib clinical trials for patients with active rheumatoid arthritis


Ann Rheum Dis. 2020 Aug 11;annrheumdis-2019-216852.doi: 10.1136/annrheumdis-2019-216852. Online ahead of print.

Kevin L Winthrop 1, Masayoshi Harigai 2, Mark C Genovese 3, Stephen Lindsey 4, Tsutomu Takeuchi 5, Roy Fleischmann 6, John D Bradley 7, Nicole L Byers 7, David L Hyslop 7, Maher Issa 7, Atsushi Nishikawa 8, Terence P Rooney 7, Sarah Witt 7, Christina L Dickson 7, Josef S Smolen 9, Maxime Dougados 10

Author Information

1 Division of Infectious Diseases, Oregon Health and Science University, Portland, Oregon, USA winthrop@ohsu.edu.

2 Department of Rheumatology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.

3 Division of Immunology and Rheumatology, Stanford University, Palo Alto, California, USA.

4 Ochsner Health Center, Baton Rouge, Louisiana, USA.

5 Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.

6 Metroplex Clinical Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

7 Eli Lilly and Company, Indianapolis, Indiana, USA.

8 Lilly Japan KK, Kobe, Japan.

9 Division of Rheumatology, Department of Medicine, Medical University of Vienna, Vienna, Austria.

10 Cochin Hospital, APHP and INSERM U-1153, CRESS Paris-Sorbonne, Paris, France.


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 4 mg and placebo to week 24, including four trials with 2 mg (placebo-controlled set). Dose-response assessment was based on four studies with 2 mg and 4 mg, 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, 2 mg 84.0 (p not significant), 4 mg 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 4 mg in endemic regions. Herpes zoster (HZ) IR/100 PY was higher for baricitinib versus placebo (placebo 1.0, 2 mg 3.1 (p not significant), 4 mg 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.