Baricitinib increased overall infection risk in patients with RA
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Baricitinib was linked to increased rates of overall infections, including herpes zoster, among patients with rheumatoid arthritis but did not impact incidence of serious infections, researchers noted in the Annals of the Rheumatic Diseases.
“Like other RA therapies, JAK inhibition is associated with increased infection,” Kevin L. Winthrop, MD, MPH, of the Oregon Health & Science University, in Portland, and colleagues wrote. “Further analyses of additional and long-term data are needed to understand this association and characterize the risk versus benefit. Baricitinib, an oral selective JAK1 and JAK2 inhibitor, demonstrated significant clinical efficacy in phase 3 RA trials.”
To analyze the incidence of infection among patients with RA who received baricitinib (Olumiant, Eli Lilly & Co.), Winthrop and colleagues examined data from eight double-blind, randomized trials, including four Phase 3, three Phase 2 and one Phase 1b studies, as well as one ongoing, Phase 3 long-term extension trial. In all, the researchers summarized 6 years of data up to April 1, 2017. Participants included 3,492 patients who received baricitinib for 7,860 patient-years. This “all-bari-RA” set included patients who received any baricitinib dose.
Comparisons with placebo were based on six studies with 4mg doses of baricitinib and placebo to week 24, including four trials with a 2mg placebo-controlled set. In addition, the researchers based their dose-response assessments on four studies with 2mg and 4mg doses, including long-term extension data.
According to the researchers, treatment-emergent infections were higher among baricitinib groups compared with placebo, with an exposure-adjusted incidence rate of 75.9 per 100 patient-years for placebo, 84 per 100 patient-years for 2-mg doses of baricitinib and 88.4 per 100 patient-years for the 4-mg baricitinib groups. Meanwhile, the incident rates for serious infection were similar across all baricitinib groups — at 3 per 100 patient-years — and placebo groups, and were stable over time.
In all, there were 11 cases of tuberculosis, with an incidence rate of 0.1 per 100 patients years in the all-bari-RA set. All tuberculosis cases occurred among those in the 4-mg groups in endemic regions. The incidence rate of herpes zoster was higher among those who received baricitinib compared with placebo, with a rate of 1 for placebo, 3.1 for the 2-mg baricitinib group 3.1 and 4.3 in the 4-mg group. These rates remained elevated and stable over time. Opportunistic infections, including multi-dermatomal herpes zoster, were infrequent among those who received baricitinib.
“The incidence rate for serious infection was similar to what has been reported in other JAK trials for RA,” Winthrop told Healio Rheumatology. “The types and frequencies of opportunistic infections were also similar to other JAK inhibitors in RA where studied, most notably tuberculosis and herpes zoster, the risks of which appear dose dependent. Both tuberculosis and herpes zoster are preventable. Screening for TB is imperative prior to JAK use, and Shingrix [(GlaxoSmithKline)] is currently being evaluated in the RA setting with regard to efficacy in preventing herpes zoster.”
Perspective
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Carlos M. Alonso, MD, FACR, RhMSUS
Most DMARDs used in the treatment of RA and other inflammatory diseases are associated with an increase in infectious events —baricitinib is no exception. The data presented shows an overall increase in treatment-emergent events including tuberculosis and herpes zoster in patients receiving at least one dose of baricitinib. For these two particular infections, the association is dose dependent. All cases of TB occurred in patients taking the 4 mg dose.
Interestingly, of the 11 cases of overt TB in the baricitinib groups, seven patients had negative TB test results at screening. HZ cases were statistically significantly higher for the 4 mg but not the 2 mg group. HZ was more common among Asian patients. Nonetheless, the incidence rate of serious infections was similar for baricitinib vs. placebo.
The data presented reaffirms what our clinical experience had taught us and is comparable to the information obtained from other clinical trials of biologic DMARDs and JAK inhibitors. Based on this study and previously published data, the 2 mg dose of baricitinib — the only dose currently approved in the U.S. — is associated with less TB and HZ cases.
The more we examine and analyze data to characterize differences in the rates and types of infections and other adverse events associated with all available DMARDs, the better we can adjust and target our treatment based on individual patient characteristics, health insurance companies permitting. Articles like this one provide information needed to help us achieve this goal.
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