SAN DIEGO — For patients with atopic dermatitis, oral medications could replace injections if dramatic results from two phase 2 trials are confirmed.
"It's a very exciting time," said Emma Guttman, MD, PhD, from the Icahn School of Medicine at Mount Sinai in New York City, who presented results from a phase 2 trial of upadacitinib (AbbVie) here at the American Academy of Dermatology 2018 Annual Meeting, where a similar trial of baricitinib (Eli Lilly) was also presented.
"For many years, patients didn't have safe treatment," she told Medscape Medical News. "The only approved oral treatment in the United States is prednisone, which has terrible side effects for long-term use. And many times, when you stop it, the disease comes back even worse."
The new oral drugs have yet to be compared directly with each other, or with injections of dupilumab, because no head-to-head studies have been conducted and the study designs are different, said Guttman, but results have been encouraging enough to raise hopes about a comparable effect.
Dupilumab "revolutionized" the treatment of moderate to severe atopic dermatitis, she explained. In the identical SOLO 1 and SOLO 2 trials (N Engl J Med. 2016;375:2335-2348), about half the patients achieved a 75% improvement in Eczema Area and Severity Index score (EASI-75) after receiving injections every other week for 16 weeks.
In the SOLO studies, the incidence of herpes viral infections increased and 7% to 12% of patients receiving dupilumab developed conjunctivitis, but neither of these adverse events was considered serious, said David Eric Cohen, MD, from New York University in New York City, during his overview of new atopic dermatitis treatments at the meeting.
Both upadacitinib and baricitinib work by inhibiting Janus kinases (JAK), rather than interleukins, and neither is considered to be a biologic because the manufacturing is conventional; the drugs are not created in cells, as biologics such as dupilumab are.
In the upadacitinib study, the 166 participants were randomized to once-daily monotherapy with upadacitinib 30 mg, 15 mg, or 7.5 mg, or placebo.
At 16 weeks, significantly more patients in the upadacitinib groups than in the placebo group achieved EASI-90 and an Investigator Global Assessment (IGA) score of 0 or 1, indicating complete or almost complete resolution of symptoms. And in the upadacitinib groups, improvements in itch were huge.
Table. Upadacitinib Outcomes at 16 Weeks
Table. Upadacitinib Outcomes at 16 Weeks
|Outcome||Upadacitinib 30 mg, %||Upadacitinib 15 mg, %||Upadacitinib 7.5 mg, %||Placebo, %|
|Mean change in EASI score||74***||62***||39*||23|
|Mean change in itch score||69***||48***||40**||10|
*P < .05, **P < .01, ***P < .001
"These results are very impressive," Guttman said.
The approach was slightly different in the randomized trial of oral baricitinib. The 124 participants were allowed to apply topical corticosteroids while they received once-daily baricitinib 4 mg, 2 mg, or placebo.
Symptom improvement was better in the baricitinib groups than in the placebo group. And more patients in the 4 mg group than in the placebo group achieved an EASI-50 at 16 weeks (61% vs 37%).
Improvement in 28-point Patient-Oriented Eczema Measure (POEM) scores were better in the 4 mg baricitinib group than in the placebo group (–7.5 vs – 3.5; P = .011), and in the 2 mg group than in the placebo group (–6.4 vs – 3.5; P = .07).
Treatment-emergent adverse events were reported by 71% of patients in the 4 mg group, 46% in the 2 mg group, and 49% in the placebo group.
"In a nutshell, baricitinib worked quite well, particularly for itch and sleep disturbance," said Jonathan Silverberg, MD, PhD, MPH, from Northwestern University in Chicago, who presented the findings. "And in a subset of more severe patients, we saw even better results."
This study also established a dose–response effect, he told Medscape Medical News. "There was a clear benefit for 4 mg."
The good news at the meeting didn't stop there. Preliminary results from a study of a new injected biologic, ANB020 (AnaptysBio), were also striking.
Unlike dupilumab, which inhibits IL-4R, ANB020 inhibits IL-33. Fifteen days after a single injection, 75% of patients achieved EASI-50, and the effects lasted at least up to day 57. However, the results are very preliminary; there were only 12 patients in this phase 2 study, and no placebo group.
"Several other promising new treatments have also shown good phase 2 results," Cohen reported. "These newer targeted therapies are going to get us better efficacy and, hopefully, fewer side effects."
The upadacitinib trial was funded by AbbVie. The baricitinib trial was funded by Eli Lilly. The ANB020 trial was funded by AnaptysBio. Guttman reports financial relationships with AbbVie, Allergan, Almirall, Anacor, AnaptysBio, Asana, Biosciences, Celgene, Concert, DBV Technologies, Dermira, DS Biopharma, Galderma, Gilead, Glenmark, Innovaderm, Kyowa Kirin, Leo Pharma, Lilly, MedImmune, Mitsubishi Tanabe, Novartis, Pfizer, Puricore, Regeneron, Sanofi, Stiefel/GSK, Sun Pharma, Vitae, Ziarco. Cohen reports financial relationships with Bickel Biotechnology, Dermira, Facilitation of International Dermatology Education, Ferndale Laboratories, Medimetriks Pharmaceuticals, and Novartis. Silverberg reports financial relationships with AbbVie, Eli Lilly, Galderma, GlaxoSmithKline, Kiniksa, Leo, Menlo, Pfizer, Realm-1, Roivant, and Regeneron-Sanofi.
American Academy of Dermatology (AAD) 2018 Annual Meeting: Abstracts 6684, 6533, and 6658. Presented February 17, 2018.
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Cite this: Oral Eczema Treatments Generate Excitement - Medscape - Feb 21, 2018.