Baricitinib, a once-daily oral inhibitor of Janus kinase (JAK) 1 and 2, significantly improved the signs and symptoms of atopic dermatitis compared with the placebo arm treated with a topical corticosteroid alone, according to results of a randomized Phase II study presented here at the 26th European Academy of Dermatology and Venereology (EADV) Congress in Geneva.
The results, described here in an oral presentation by Emma Guttman-Yassky, M.D., Ph.D., provide further evidence that JAK inhibition is a promising targeted strategy that may benefit patients with moderate to severe atopic dermatitis (AD).
“I think this potentially provides a new oral treatment that can be used in moderate to severe patients with or without topical steroids,” Dr. Guttman-Yassky said in an interview with Dermatology Times. “It seems efficacious and safe, so we are very excited so far to have a possible new oral therapy for AD to chronically treat our patients.”
The primary objective of the study was percent of the patients that achieved a reduction in disease severity of at least 50 percent as measured by the Eczema Area and Severity Index (EASI-50). After 16 weeks of treatment with 4 mg baricitinib daily in combination with a topical steroid, 61 percent of patients (n = 38) achieved EASI-50, compared with 37 percent of patients (n = 49) treated with topical corticosteroid alone (P < 0.05), according to Dr. Guttman-Yassky, vice chair for research and director of the Laboratory of Inflammatory Skin Diseases at the Icahn School of Medicine at Mount Sinai Medical Center, New York.
The new findings with baricitinib represent the latest data suggesting JAK inhibition is a promising treatment strategy in the setting of atopic dermatitis. Just about a week before EADV, it was reported in a press release that a phase 2b study of upadacitinib (ABT-494), a JAK1 inhibitor, met its primary endpoint of greater mean percentage change from baseline in Eczema Area and Severity Index (EASI) score for once-daily treatment versus placebo in AD patients at 16 weeks.
Topical delivery of JAK inhibitors may also be an option for patients with mild to moderate disease. Tofacitinib, the JAK inhibitor approved as an oral treatment of adult patients with moderate to severe rheumatoid arthritis, has been studied in an ointment formulation in the setting of atopic dermatitis. In a report on a phase 2a randomized trial of tofacitinib ointment published in the British Journal of Dermatology, investigators said the treatment, applied topically, had a safety and local tolerability comparable to vehicle, with significantly greater efficacy vs. vehicle in improving disease severity and pruritus.
However, Dr. Guttman-Yassky said she hopes oral JAK inhibitors may provide a potential alternative option for atopic dermatitis patients who can’t achieve control with topical treatments, including topical corticosteroids.
“When patients come to me, many times they have already tried all the topicals you can imagine,” Dr. Guttman-Yassky said. “When more than 10 percent body surface area is involved, patients will likely need systemic treatment, and our options are relatively limited for systemic treatments in moderate-to severe AD patients.”
Dupilumab, the monoclonal antibody approved in March 2017 for moderate to severe atopic dermatitis, is clearly one novel and effective option for systemic treatment. However, it is administered by subcutaneous injections every two weeks, and “not everybody wants an injection,” Dr. Guttman-Yassky said. “We are also in desperate need for safe oral medications for atopic dermatitis for long term use.”
To evaluate the safety and efficacy of baricitinib in patients with moderate-to-severe atopic dermatitis, Dr. Guttman-Yassky and colleagues conducted a 16-week Phase II randomized, double-blind, placebo-controlled study including a total of 124 patients randomized 4:3:3 to placebo, baricitinib 2 mg once daily, or baricitinib 4 mg once daily.
All patients received background treatment with a mid-potency topical corticosteroid (Triamcinolone 0.1% cream) starting four weeks before randomization. “In this study, we are simulating the real-life situation in which often patients actually use topical steroids together with a systemic treatment,” Dr. Guttman-Yassky said.
As noted, baricitinib 4 mg once daily was superior to topical corticosteroid alone in achievement of EASI-50 at 16 weeks. In addition, 57 percent of patients in the baricitinib 2 mg group (n = 37) achieved EASI-50, though the result approached statistical significance vs corticosteroid alone (p = 0.065), but “we must remember that the sample size was small and patients already received topical steroids for four weeks prior to randomization, which reduced the baseline EASI and may have minimized differences between treatment arms and placebo,” Dr. Guttman-Yassky said.
The improvement associated with baricitinib was noted early, according to Dr. Guttman-Yassky, who noted that at four weeks, EASI-50 was achieved in 68 percent of patients in the baricitinib 4 mg group and 62 percent of the 2 mg group, compared with 16 percent of patients in the topical corticosteroid only group (P < 0.001).
Adverse events that emerged during treatment were reported in 49 percent of patients treated with topical corticosteroid only, 46 percent of patients in the baricitinib 2 mg group, and 71 percent of the 4 mg group. The most common events in the 4 mg group were upper respiratory tract infections and nasopharyngitis, headache, and asymptomatic increases in creatine phosphokinase (CPK). No herpes zoster cases were seen.
“Overall, the drug was very well tolerated,” Dr. Guttman-Yassky said, who noted that a Phase III investigation of baricitinib for atopic dermatitis is in the planning stages.
What’s next for baricitinib?
Along with other JAK inhibitors, baricitinib may have other potential roles in the treatment of other inflammatory conditions, such as systemic lupus erythematosus. In addition, a Phase III program for baricitinib in psoriatic arthritis is expected to begin in 2018.
In February 2017, baricitinib was approved in the European Union for treatment of adults with moderate to severe active rheumatoid arthritis, and a New Drug Application for this indication will be resubmitted to the U.S. Food and Drug Administration (FDA) before end of January 2018.