The rheumatoid-arthritis drug baricitinib, an oral selective Janus-kinase inhibitor, reduces symptoms of moderate to severe atopic dermatitis (AD) for at least 68 weeks, an extension study of two randomized controlled trials shows. "Baricitinib would be used in patients with moderate-to-severe AD who had an inadequate response to topical therapy," lead author Dr. Jonathan Silverberg of George Washington University School of Medicine and Health Sciences, in Washington, D.C., told Reuters Health by email. There are few good options for patients who need long-term systemic therapy for AD. Baricitinib is approved in the EU and Japan to treat moderate to severe AD in adults, but in the U.S. is only indicated for rheumatoid arthritis. "Right now the only drugs approved (in the U.S.) are dupilumab and systemic steroids. The latter are fraught with side effects," said Dr. Mark Lebwohl, chairman emeritus of the dermatology department at the Icahn School of Medicine at Mount Sinai, in New York City, who was not involved in the research. He told Reuters Health by email that the new study, called BREEZE-AD3 and published in JAMA Dermatology, is "the first demonstration of a durable response of atopic dermatitis to baricitinib. Equally important, no safety issues were demonstrated over the course of the study." BREEZE-AD3 is an ongoing, double-blind extension of the earlier phase-3 BREEZE-AD1 and BREEZE-AD2 trials and is taking place at sites across Europe, Asia, Latin America, and Australia. Patients classified as responders or partial responders in the earlier (16-week) studies were eligible to enroll in BREEZE-AD3, and 221 did so. Responders and partial responders had scores of 0 or 1 and 2, respectively, on the validated Investigator Global Assessment for AD (vIGA-AD) and had not received rescue therapy during the original studies. BREEZE-AD3 efficacy results were reported for 124 patients who had received baricitinib 2 mg or 4 mg (as opposed to 1 mg). Of these, 90 remained in the ongoing study as of this report. Of the 70 patients receiving baricitinib 4 mg, 45.7% had reached a vIGA-AD score of 0 or 1 at BREEZE-AD3 baseline, and 47.1% achieved or retained such a score at week 68. Of the 54 patients receiving baricitinib 2 mg, the numbers were 46.3% and 59.3%, respectively. At week 16, 74.1% of the patients had achieved 75% or more improvement in the Eczema Area and Severity Index. By week 68, this proportion had rising to 81.5%. "A recent publication provided an integrated summary of the safety of baricitinib, 4 and 2mg, in AD, with pooled data from 8 randomized clinical trials, including BREEZE-AD3; hence, a separate evaluation of safety was not performed in this smaller data set," the researchers write. "The integrated analysis revealed a low (<2.5%) frequency of serious adverse events, which was no higher than observed incident rates in placebo-treated patients," they add. "Nasopharyngitis, headache, creatine kinase level elevations, and diarrhea were the most common treatment- emergent adverse events with baricitinib. An initial increase in herpes simplex infections compared with placebo was apparent in the first 16 weeks, but there was no evidence of an increased incidence of herpes infection with prolonged treatment and no increases in skin infections requiring antibiotic treatment, major adverse cardiovascular events, or conjunctival disorders with baricitinib treatment." Dr. Lebwohl noted that Janus-kinase inhibitors such as baricitinib "are safer than other currently used (off-label) oral agents for atopic dermatitis, like cyclosporine, methotrexate, mycophenolate and azathioprine, which will likely be replaced by the Janus kinase inhibitors." BREEZE-AD3 was sponsored by Eli Lilly and Co., maker of baricitinib. Dr. Silverberg and several of his coauthors report financial ties to the company. —Scott Baltic Source
