Infections in Baricitinib Clinical Trials for Patients with Active Rheumatoid Arthritis
Winthrop KL, Harigai M, Genovese MC, Lindsey S, Takeuchi T, Fleischmann R, Bradley JD, Byers NL, Hyslop DL, Issa M, Nishikawa A, Rooney TP, Witt S, Dickson CL, Smolen JS, Dougados M. - Annals of the Rheumatic Diseases, May 2020
Baricitinib, an oral selective JAK1 and JAK2 inhibitor,8 demonstrated significant clinical efficacy in phase 3 RA trials. Pooled data from these trials, including a long-term extension (LTE), inform the safety profile for baricitinib, mainly to evaluate the incidence of infection in patients with active rheumatoid arthritis (RA), with a focus on serious infection, tuberculosis (TB), herpes zoster (HZ) and opportunistic infection (OI).
The data collected were from eight double-blind randomised trials (four phase 3, three phase 2 and one phase 1b) and one ongoing phase 3 LTE trial, with data up to 6 years (as of 1 April 2017). Each baricitinib dose was compared with placebo using the Cochran-Mantel-Haenszel test stratified by study.
The results showed, increased rates of treatment-emergent infections including herpes zoster (HZ) in patients with RA treated with baricitinib. The incidence of serious infection did not increase with baricitinib versus placebo in the 24-week randomised, controlled period but was similar to that reported in other recent tsDMARD and bDMARD development programmes. There were 11 cases of tuberculosis reported within the baricitinib RA programme; albeit, these reports occurred in endemic regions. Opportunistic infections in general, excluding HZ, were infrequent in the programme.
This study might impact clinical practice or future developments by ensuring that screening and treatment for latent tuberculosis infection should be employed prior to starting baricitinib. The data further highlight the importance of HZ vaccination and prevention in the setting of JAK inhibition.