EXPERT ANALYSIS FROM THE COASTAL DERMATOLOGY SYMPOSIUM
Atopic dermatitis (AD) that becomes chronic and persists into adulthood often becomes less responsive to topical treatment with mid- to high-potency corticosteroids and calcineurin inhibitors, necessitating a different approach.
In these older AD patients, long-term treatment with systemic therapy frequently is used to prevent flare-ups and improve patient quality of life. Joseph F. Fowler Jr., MD, discussed these treatment options at the annual Coastal Dermatology Symposium.
Older systemic medications
These include methotrexate, mycophenolate mofetil, cyclosporine, azathioprine, and retinoids. Methotrexate is predictably effective, and dermatologists generally are comfortable with it. The drug requires monitoring for adverse effects along with other precautions, similar to its use in psoriasis.
Retinoids may be most effective in psoriasiform hand dermatitis and is appropriate for some patients, but teratogenicity is a concern, he said at the symposium jointly presented by the University of Louisville and Global Academy for Medical Education.
Mycophenolate mofetil is useful when the adverse event profiles of azathioprine, methotrexate, and cyclosporin A eliminate them from consideration, but it tends to confer slower improvement and has less efficacy overall.
Cyclosporin A led to successful outcomes in 77% of patients and mild improvement in 16% of patients in one trial, with milder side effects than those commonly seen in transplant patients. There was no increased risk of nephrotoxicity or hypertension over 6 months of treatment. The drug is useful for short-term control of flares and in contact dermatitis when corticosteroids are contraindicated, according to Dr. Fowler of the department of dermatology and director of occupational dermatitis at the University of Louisville (Ky.). It is the only drug other than corticosteroids that offers rapid improvement.
Newer drug options
One is dupilumab (Dupixent), an antibody that blocks interleukin (IL)–4 and IL-13. It received Food and Drug Administration approval in March 2017 for moderate to severe atopic dermatitis that doesn’t respond to topical treatment. Most patients get at least some benefit from the injectable drug, and some get a strong benefit, according to Dr. Fowler, although he pointed out that it can take 12 weeks before it achieves maximum effect. The initial dose is 600 mg administered subcutaneously, followed by 300 mg every 2 weeks. At 16 weeks, it reduced Eczema Area and Severity Index (EASI) scores by about 75% in patients taking a 300 mg dose every other week, compared with about a 20% decline in placebo.
The IL12/23 inhibitor ustekinumab (Stelara), approved for psoriasis and psoriatic arthritis, was effective in a case series of three patients. It led to a greater than 50% reduction in EASI score at week 16, following doses with 45 mg at weeks 0, 4, and 12. Biopsies revealed reductions in Th22 cells and cytokine levels. But, as a caveat, Dr. Fowler reported personal communication with two eczema experts who said they had seen little or no effect with ustekinumab in 10 patients.
The Janus kinase inhibitor tofacitinib, approved for rheumatoid arthritis, also is under investigation for AD. A trial in six patients who had not achieved adequate control with methotrexate or azathioprine showed a 67% improvement in the SCORAD (Scoring Atopic Dermatitis) index at doses of 5 mg of tofacitinib twice per day in five patients and 5 mg every other day in one patient, he said.
The PDE-4 inhibitor apremilast, approved for psoriasis and psoriatic arthritis, has been reported to improve AD symptoms in individual patients. Celgene demonstrated some improvement in a clinical trial of apremilast at doses of 30 or 40 mg twice per day, but the company isn’t pursuing AD as an indication, he noted.
Dr. Fowler has consulted for Abbvie, IntraDerm, and SmartPractice. He is on the speaker’s bureaus of SmartPractice and Regeneron/Sanofi. He has been a research investigator for Abbvie, Allergan, Amgen, Bayer, Dow, Galderma, Genentech, InnovaDerm, Johnson & Johnson, Lilly, Merck, Novartis, Pfizer, Precision Dermatology, Regeneron, SmartPractice, Taro, and Valeant.