Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

Efficacy and Safety of Lowering Dupilumab Frequency for AD

Key clinical point: The approved regimen of 300 mg of dupilumab every 2 weeks appears best for long-term treatment.

Major finding: Longer dosing intervals and placebo resulted in reduced response and no safety advantage, respectively.

Study details: A 36-week, randomized, double-blind, placebo-controlled study of 422 patients who were treated successfully in previous trials.

Disclosures: The trial was funded by Sanofi and Regeneron. Dr. Worm reported receiving honoraria for consulting and lecture activity from Regeneron and Sanofi during and outside the conduct of the study, among other disclosures. The other authors had multiple disclosures related to these and multiple other pharmaceutical companies, or were employees of Sanofi or Regeneron.

Citation:

Worm M et al. JAMA Dermatol. 2019 Dec 26. doi: 10.1001/jamadermatol.2019.3617.

Commentary:

The desire to decrease or stop a therapy such as dupilumab may be motivated by cost, current and potential adverse effects, and individual needs. Because atopic dermatitis is a waxing-and-waning disease with a predilection for cycles of escalation, there is some thought a priori that reduced treatment schedules or discontinued use of a drug may be possible in a state of low disease activity.

The investigators of the SOLO-CONTINUE trial found, however, that continuous treatment with the dosage used in the original SOLO trials (300 mg weekly or every 2 weeks) resulted in a better maintenance of response than a less-frequent dosage and was significantly better than placebo for all endpoints. The less-frequent dosage regimens (every 4 weeks and every 8 weeks), on the other hand, produced some dose-dependent reduction in efficacy.

The development of antidrug antibodies was found in approximately 11% of individuals who received placebo or dupilumab every 8 weeks, 6% of the monthly treatment group, and only 1% in the weekly group, suggesting that less-frequent administration results in higher immunogenicity. However, most of the antidrug antibody levels were low and did not seem to have any clinical effect, making this finding of uncertain relevance to patient care.

The study is valuable because, as more patients are exposed to the drug, more will want or need to reduce the dosage or stop use over time – and although it seems optimal to continue an every-2-weeks treatment regimen, this may not always be feasible. As we integrate new therapies and learn more about atopic dermatitis, it is important that we understand the options and implications around decreasing the dosage of dupilumab. This newly concluded trial is helpful in this regard.

Peter A. Lio, MD, is with the department of dermatology at Northwestern University, Chicago, and the Chicago Integrative Eczema Center. He reported receiving grants and personal fees from Regeneron, Sanofi Genzyme, and other companies, as well as other disclosures. His comments appear in JAMA Dermatology (2019 Dec 26. doi: 10.1001/jamadermatol.2019.3331).