an industry-sponsored study reports.
“In this post hoc analysis, both the efficacy and the safety profiles of abrocitinib were consistent in patients with moderate-to-severe atopic dermatitis, regardless of prior biologic therapy use,” lead author Melinda Gooderham, MD, medical director of the SKiN Centre for Dermatology, Peterborough, Ont., said during an oral presentation at the Society for Investigative Dermatology (SID) 2022 Annual Meeting.
“These results ... support the use of abrocitinib in patients who might have received biologic therapy prior,” she added.
“Prior biologic use did not reveal any new safety signals ... keeping in mind the key limitation of this analysis is that it was done post hoc,” she noted.
Guidelines for moderate-to-severe atopic dermatitis refractory to topical or systemic therapy include systemic immunosuppressants and dupilumab, a monoclonal antibody that inhibits interleukin-4 and interleukin-13 cytokine-induced responses, Dr. Gooderham said.
The Food and Drug Administration recently approved abrocitinib, an oral once-a-day Janus kinase 1 (JAK1) inhibitor, to treat the disease. The approval came with a boxed warning about increased risk for serious infections, mortality, malignancy, and lymphoproliferative disorders, major adverse cardiovascular events, thrombosis, and laboratory abnormalities.
Comparing the bio-experienced with the bio-naive
Dr. Gooderham and colleagues investigated whether patients who’d been treated with a biologic would respond to abrocitinib differently than patients who had not received prior biologic treatment.
Researchers pooled data from two phase 3 placebo-controlled trials of abrocitinib that led to approval and an earlier phase 2b study. They identified 67 patients previously treated with dupilumab and 867 patients who were bio-naive. They repeated their analysis using data from another phase 3 study of abrocitinib on 86 patients previously treated with dupilumab and 1,147 who were bio-naive. On average, the bio-experienced patients were in their mid-30s to early 40s, and the bio-naive group was several years younger.
In the pooled phase 2b and phase 3 JADE MONO-1 and JADE MONO-2 monotherapy trials, patients received once-daily abrocitinib 100 or 200 mg or placebo for 12 weeks. In the phase 3 JADE REGIMEN, which they analyzed separately, eligible patients were enrolled in a 12-week open-label run-in period during which they received an induction treatment of abrocitinib 200 mg once a day.
Researchers compared results of two assessments: the IGA (Investigator Global Assessment) and EASI-75 (Eczema Area and Severity Index, 75% or greater improvement from baseline).
- At week 12, IGA 0/1 dose-dependent response rates were similar in the pooled groups, regardless of whether they had received prior biologic therapy. With abrocitinib 200 mg, 43.5% of those with prior dupilumab therapy responded versus 41.4% of bio-naive patients; with abrocitinib 100 mg, 24.1% versus 26.7% responded. In JADE REGIMEN, corresponding response rates with abrocitinib 200 mg were 53.5% versus 66.9%, respectively.
- At week 12, EASI-75 responses were also comparable. In the pooled groups by dose, with abrocitinib 200 mg, EASI-75 response rates were 65.2% in patients with prior dupilumab therapy versus 62.4% in those without; at abrocitinib 100 mg, 34.5% versus 42.7% responded. Corresponding rates in JADE REGIMEN were 64.0% versus 76.4%, respectively.
- Treatment-emergent adverse event rates among patients with versus without prior biologic therapy were, respectively, 71.7% versus 69.9% (abrocitinib 200 mg + 100 mg groups) in the pooled population. Rates in JADE REGIMEN with abrocitinib 200 mg were, respectively, 66.3% versus 66.5%.
- Abrocitinib efficacy and safety were consistent in patients with moderate-to-severe atopic dermatitis, regardless of prior biologic therapy. Adverse events in the pooled monotherapy trials and in JADE REGIMEN included acne, atopic dermatitis, diarrhea, headache, nasopharyngitis, nausea, upper abdominal pain, and upper respiratory tract infection.
The authors acknowledge that the post hoc study design is a limitation and recommend confirming these findings in a large, long-term prospective study.
JAK inhibitors expand treatment options
The results will help doctors treat their patients, Jami L. Miller, MD, associate professor of dermatology and dermatology clinic medical director at Vanderbilt University Medical Center, Nashville, Tenn., told this news organization.
“Because JAK inhibitors have potentially more side effects than inhibitors of interleukin-4 and interleukin-13, in clinical practice most dermatologists are more likely to treat patients first with dupilumab or similar meds and step up to a JAK inhibitor if they do not respond,” she added in an email.
“With more meds coming out to meet the needs of this population, this is an exciting time for patients with moderate-to-severe atopic dermatitis,” she commented.
Lindsay C. Strowd, MD, associate professor and vice chair of the department of dermatology at Wake Forest University, Winston-Salem, N.C., said JAK inhibitors are increasingly being studied and approved for use in various dermatologic diseases.
An oral JAK inhibitor (upadacitinib) is currently FDA approved for moderate-to-severe atopic dermatitis, and a topical JAK inhibitor (ruxolitinib) is also approved for use in atopic dermatitis, Dr. Strowd noted.
“The study results give providers important practical information,” added Dr. Strowd, who also was not involved with the study. “Those of us who care for patients with severe atopic dermatitis need to know how patients with prior biologic exposure will respond as newer agents come to market and the options for biologic use in atopic dermatitis continue to grow.”
The study was sponsored by Pfizer. All study authors have reported relevant financial relationships with, and several authors are employees of, Pfizer, the developer of abrocitinib. Dr. Strowd and Dr. Miller have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.