PracticeUpdate Conference Series World Congress of Dermatology 2019

Dupilumab Offers Clinically Meaningful Benefit for Adolescent Atopic Dermatitis Findings suggest that Investigator Global Assessment may not fully capture the value of medication for patients.

T he interleukin (IL)-4- and IL-13-inhibiting human monoclonal antibody dupilumab offers ado- lescent patients with moderate-to-severe atopic dermatitis clinically meaningful responses, even when Investigator Global Assessment (IGA) scores are >1, according to a post hoc analysis of a phase III trial. Among all dupilumab-treated adolescent atopic der- matitis patients with an IGA score >1 at week 16, a majority of patients achieved a clinically meaningful improvement, either in dermatitis signs, symptoms, quality of life, or a combination, relative to placebo. “The IGA is a primary endpoint required by the FDA because it maps nicely to terms that the public understands,” study investigator Amy S. Paller, MD, of Northwestern University in Chicago, told Elsevier’s PracticeUpdate . “However, to achieve ‘clear’ [IGA 0] or ‘almost clear’ [IGA 1] when starting with moderate-to-severe disease is a very high bar to achieve and is not consonant with what is meaningful change to patients with atopic dermatitis.” Thus, instead of only investigating IGA response as a meaningful endpoint, three “other mean- ingful endpoints were evaluated. These were ≥50% improvement in baseline Eczema Area and Severity Index (EASI), ≥3-point improvement in average weekly Peak Pruritus Numerical Rating Scale (NRS) score, and ≥6-point improvement in Children’s Dermatology Life Quality Index (CDLQI).” “In the group that did not achieve IGA 1 or 0, clinically meaningful improvements were seen in all three of these endpoints,” Paller added. “The majority of adolescents treated with dupilumab who did not achieve IGA 0 or 1 at week 16 did achieve clinically meaningful improvement.” The investigators randomized 251 patients between 12 and 17 years of age 1:1:1 to receive 16 weeks of subcutaneous dupilumab 300 mg every 4 weeks, subcutaneous dupilumab every 2 weeks (200 mg or 300 mg according to weight), or placebo. At week 16, 69 of 84 patients (82.1%) on the monthly dosing scheme had IGA scores >1, as did 62 of 82 patients (75.6%) on the biweekly dosing scheme. Of the patients receiving placebo, 83 of 85 (97.6%) had IGA scores >1. However, 55.1% of patients on the monthly dosing scheme and 74.2% of patients on the biweekly dosing scheme achieved the com- posite clinically meaningful improvement endpoint at week 16, compared with 21.7% of patients receiv- ing placebo (P < .0001).

Dr. Amy S. Paller

As many as 44.9% of patients on the monthly dosing scheme achieved ≥50% improvement in baseline EASI, as did 48.4% of patients on the biweekly dosing scheme, compared with 10.8% of patients receiving placebo (P < .001). A ≥3-point improvement in average weekly Peak Pruritus NRS score was achieved in 30.4% of patients on the monthly dosing scheme and in 43.5% of patients on the biweekly dosing scheme, compared with 7.2% in patients receiving placebo (P < .001). Similarly, a ≥6-point improvement in CDLQI score was observed in 43.5% of patients on the monthly dosing scheme and in 51.6% of patients on the biweekly dosing scheme, compared with 16.9% in patients receiving placebo (P < .001). Dr. Paller noted that these results remind inves- tigators that “the IGA results are not indicative of the value of a medication for affected patients and that clinically meaningful results for dupilumab are achieved in the majority of those treated. “We now have the opportunity to see real-world data about use in adolescents and to advance the medication to younger children with atopic dermatitis,” she concluded. Dr. Paller added that there were “no unexpected safety issues” observed during the trial; however, “while safety has been well-demonstrated in adults and adolescents, future trials and then use after commercial [release] will be important in further assuring safety and in looking at drug durability”.

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WCD 2019 • PRACTICEUPDATE CONFERENCE SERIES 17