Long-term data for dupilumab in atopic dermatitis (AD; ICD 10 code L20) revealed at the American Academy of Dermatology (AAD) 75th Annual Meeting reflect safety, rapid relief of troublesome symptoms and a long-lived response in keeping with the drug’s breakthrough status, experts told Dermatology Times.
Key CHRONOS data
The 52-week phase 3 randomized, double-blind, placebo-controlled study to demonstrate the efficacy and long-term safety of dupilumab in adult patients with moderate-to-severe atopic dermatitis (CHRONOS ) trial randomized a total of 740 patients to placebo plus topical corticosteroids (TCS), versus weekly or every other week dupilumab 300 mg injections plus TCS.
Before CHRONOS, said principal CHRONOS investigator Andrew Blauvelt, M.D., M.B.A., most previous dupilumab studies in AD involved with monotherapy and lasted only 16 weeks.1 He is president of the Oregon Medical Research Center.
Emma Guttman-Yassky, M.D., Ph.D., says, “Usually you need to do monotherapy trials in atopic dermatitis to see if the drug works compared to placebo. And this has indeed been done with dupilumab. However, what’s important about CHRONOS is that this trial is showing a real-life situation where topical steroids are used together with systemics, and this is the first trial that shows that dupilumab maintains its efficacy and safety long-term.”
She is professor and vice chair, department of dermatology, Icahn School of Medicine at Mount Sinai.
Dr. Blauvelt adds that although prior monotherapeutic studies have shown remarkable efficacy, investigators added TCS because, “we know from prior dupilumab studies that 100% of patients are not 100% clear” after therapy.
Dr. Guttman-Yassky says CHRONOS is “the first study going up to one year, showing that patients did not lose their efficacy, and that adding topical steroids delivers some added benefits. Most importantly, patients did not lose response. That is important with a systemic drug. We’re always afraid with cyclosporine, for example, that it works very well initially. It hits hard. But many patients lose efficacy with cyclosporine after a few months. Here we don’t see that. We see continued efficacy and safety going out to one year.”
Regarding primary endpoints, 39% of CHRONOS patients who received either dupilumab dose achieved clear or almost clear skin (investigator global assessment/IGA 0 or 1) at week 16, versus 12% of placebo-treated patients (p<0.0001).2 Among key secondary endpoints, 40% of patients who received weekly dupilumab and 36% of those who received every other week treatments achieved IGA 0 or 1 at week 52. The corresponding percentage among the placebo group was 12.5% (p<0.0001).
Dr. Blauvelt says, “You can tell by the 39% response rate that IGA 0/1 is a difficult bar to achieve. That doesn’t mean that the drug is only 40% effective. Dupilumab works well and quickly with no loss of efficacy between week 16 and 52.” The proportions of patients who achieved a 75% reductions in Eczema Area and Severity Index (EASI 75) results at week 16 were 64% and 69% for dupilumab, versus 23% placebo (p<0.0001). The fact that the study delivered better results than previous monotherapeutic trials “makes sense, given that patients had topical steroids in addition to dupilumab.”
Lawrence F. Eichenfield, M.D., added, “The CHRONOS study gives us good data on what to expect in terms of improvement (around 60% to 70% of patients meeting EASI 75 and around 50% EASI 90) with dupilumab and concurrent topical steroids, as well as consistent efficacy over one year of use. Week 16 showed peak clinical efficacy, maintained through week 52.” The low levels of improvement achieved by patients on placebo and topical steroids show that “while we believe topical steroids work, they provide more limited benefits than does active systemic therapy.” He is chief of pediatric and adolescent dermatology, professor of dermatology and pediatrics and vice chair, Department of Dermatology, and at the University of California, San Diego School of Medicine.
Drs. Eichenfield and Blauvelt recommended caution when comparing CHRONOS results with previous studies of biologics for psoriasis. “We’re dealing with completely different diseases and scoring systems,” said Dr. Blauvelt.
The fact that dupilumab allowed 65% of treated patients (versus 22% on placebo; p<0.0001) to reduce their EASI scores by 75% does not make dupilumab less effective than biologic drugs that post higher Psoriasis Area and Severity Index (PASI) reductions, said Dr. Blauvelt. “It’s an unfair comparison. The baseline score for these measures is much higher than baseline scores seen in psoriasis biologics studies.” In the 3 CHRONOS cohorts, median body surface area (BSA) affected ranged from 52% to 58.8%. “You never see that in a psoriasis trial,” where average BSA involved is in the 20% range, he said.