PT  - JOURNAL ARTICLE
AU  - Kevin L Winthrop
AU  - Masayoshi Harigai
AU  - Mark C Genovese
AU  - Stephen Lindsey
AU  - Tsutomu Takeuchi
AU  - Roy Fleischmann
AU  - John D Bradley
AU  - Nicole L Byers
AU  - David L Hyslop
AU  - Maher Issa
AU  - Atsushi Nishikawa
AU  - Terence P Rooney
AU  - Sarah Witt
AU  - Christina L Dickson
AU  - Josef S Smolen
AU  - Maxime Dougados
TI  - Infections in baricitinib clinical trials for patients with active rheumatoid arthritis
AID  - 10.1136/annrheumdis-2019-216852
DP  - 2020 Oct 01
TA  - Annals of the Rheumatic Diseases
PG  - 1290--1297
VI  - 79
IP  - 10
4099  - http://ard.bmj.com/content/79/10/1290.short
4100  - http://ard.bmj.com/content/79/10/1290.full
SO  - Ann Rheum Dis2020 Oct 01; 79
AB  - 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.