From the Journals

Topical tofacitinib shows promise in atopic dermatitis

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It’s time to think about head-to-head studies

With the discovery of how cytokines such as IL-4, IL-5, IL-13, and IL-31 drive inflammatory disease pathogenesis, more targeted therapies are possible for dermatologic conditions such as atopic dermatitis.

The promise of such pathogenesis-based treatments gives hope to patients with atopic dermatitis, for whom new treatments have not been brought to market in more than 15 years.

While this is reason for excitement, the emergence of several new promising therapies calls for comparison trials, according to Brett A. King, MD, and William Damsky, MD, PhD, both of Yale University, New Haven, Conn.

“Further studies will be needed to address long-term efficacy and safety,” Dr. King and Dr. Damsky noted. The results of Dr. Bissonnette’s phase IIa trial of the topical Janus kinase inhibitor tofacitinib mean there is potentially a third targeted topical agent to emerge as a treatment for atopic dermatitis. The others include the phosphodiesterase-4 inhibitor crisaborole, and dupilumab, a monoclonal antibody that targets IL-4 and IL-13.

“Head-to-head trials involving these agents and superpotent topical steroids would be useful in establishing their place in AD treatment algorithms,” Dr. King and Dr. Damsky said.

Dr. King is an assistant professor of dermatology at Yale University. His coauthor, Dr. Damsky, is a second-year resident in dermatology at Yale University. These remarks are taken from an editorial accompanying Dr. Bissonnette’s study (Br J Dermatol. 2016 Nov;175[5]:861-2). Dr. King disclosed he has industry ties with Eli Lilly and Pfizer, among others. Dr. Damsky had no relevant disclosures.


 

FROM BRITISH JOURNAL OF DERMATOLOGY

Topical tofacitinib showed significant improvements across all endpoints and for pruritus at week 4, compared with vehicle, results of a phase IIa trial have shown.

Tofacitinib is a Janus kinase inhibitor that affects the interleukin (IL)–4, IL-5, and IL-31 signaling pathways, interfering with the immune response that leads to inflammation.

The study could mean “that inhibition of the JAK-STAT pathway may be a new therapeutic target for AD,” wrote the study’s lead author, Robert Bissonnette, MD, president of Innovaderm Research in Montreal. The study was published in the British Journal of Dermatology (2016 Nov;175[5]:902-11).

In the multicenter, double-blind, controlled study of 69 adults with mild to moderate atopic dermatitis randomly assigned to either 2% tofacitinib or vehicle ointment twice daily, the study group achieved an 81.7% mean reduction in baseline Eczema Area and Severity Index (EASI) score, compared with 29.9% of controls over the 4-week study period (P less than .001). EASI scores in the study group were about 80% at a score of 50, 60% at a score of 75, and 40% at a score of 90.

By week 4, about three-quarters of the study group were either clear or almost clear of their skin condition, according to the physician global assessment scale, compared with 22% of controls (P less than .05).

There also was a rapid reduction in patient-reported pruritus in the tofacitinib group per the Itch Severity Item scale, compared with controls, at weeks 2 and 4 (P less than .001 for each time point).

Tolerability was similar across the study, and treatment-related adverse effects were mild, although 44% of the tofacitinib group did report experiencing some form of infection, infestation, or other complication. Two people in the study group dropped out because of the severity of their treatment-emergent adverse events. There were no reported severe or serious infections.

Dr. Bissonnette has numerous pharmaceutical industry relationships, including with Pfizer, the study’s sponsor.

On Twitter @whitneymcknight

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