Dupilumab prevents flares in adults with moderate to severe atopic dermatitis in a 52-week randomized controlled phase 3 trial
Authors: Joseph F. Merola, Robert Sidbury, Andreas Wollenberg, Zhen Chen, Annie Zhang, Brad Shumel, Ana B. Rossi
Journal: Journal of the American Academy of Dermatology (2020)

To the Editor: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by flares, defined as worsening of the disease requiring escalation/intensification of AD treatment.1Sidbury R. Tom W.L. Bergman J.N. et al.Guidelines of care for the management of atopic dermatitis: section 4. Prevention of disease flares and use of adjunctive therapies and approaches.J Am Acad Dermatol. 2014; 71: 1218-1233Abstract Full Text Full Text PDF PubMed Scopus (201) Google Scholar, 2Wollenberg A. Oranje A. Deleuran M. et al.ETFAD/EADV Eczema task force 2015 position paper on diagnosis and treatment of atopic dermatitis in adult and paediatric patients.J Eur Acad Dermatol Venereol. 2016; 30: 729-747Crossref PubMed Scopus (263) Google Scholar, 3Wollenberg A. Barbarot S. Bieber T. et al.Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I.J Eur Acad Dermatol Venereol. 2018; 32: 657-662Crossref PubMed Scopus (369) Google Scholar Patients experiencing flares often visit emergency departments, a costly and burdensome course of action, and are treated with systemic steroids, which are not recommended by treatment guidelines.1Sidbury R. Tom W.L. Bergman J.N. et al.Guidelines of care for the management of atopic dermatitis: section 4. Prevention of disease flares and use of adjunctive therapies and approaches.J Am Acad Dermatol. 2014; 71: 1218-1233Abstract Full Text Full Text PDF PubMed Scopus (201) Google Scholar,4Wollenberg A. Barbarot S. Bieber T. et al.Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part II.J Eur Acad Dermatol Venereol. 2018; 32: 850-878Crossref PubMed Scopus (316) Google Scholar Flare prevention is a primary goal of long-term AD disease control.2Wollenberg A. Oranje A. Deleuran M. et al.ETFAD/EADV Eczema task force 2015 position paper on diagnosis and treatment of atopic dermatitis in adult and paediatric patients.J Eur Acad Dermatol Venereol. 2016; 30: 729-747Crossref PubMed Scopus (263) Google Scholar Dupilumab, a fully human monoclonal antibody, blocks the shared receptor subunit for interleukin 4 and interleukin 13; dupilumab clinical trials have shown that these cytokines are key and central drivers of multiple type 2 inflammatory diseases. We assessed the impact of 52 weeks of dupilumab treatment on flare prevention in adults with moderate to severe AD. LIBERTY AD CHRONOS was a randomized, double-blind, placebo-controlled, phase 3 trial in adults with moderate to severe AD (NCT02260986).5Blauvelt A. de-Bruin-Weller M. Gooderham M. et al.Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial.Lancet. 2017; 389: 2287-2303Abstract Full Text Full Text PDF PubMed Scopus (586) Google Scholar This analysis included patients receiving placebo or dupilumab 300 mg every 2 weeks for 52 weeks. All patients received concomitant medium-potency topical corticosteroids (TCS). During the treatment period, the annualized flare rate was significantly higher in patients treated with TCS alone (0.77; 95% confidence interval [CI], 0.63-0.93) compared with dupilumab plus TCS (0.17; 95% CI, 0.10-0.29), a 78% relative reduction in annual flares for patients treated with dupilumab plus TCS (Fig 1). The estimated cumulative flare-free rate was greater for patients treated with dupilumab plus TCS compared with patients receiving TCS alone at all time points, with increasing differences between the treatment arms over time (Fig 2).Fig 2Kaplan-Meier curve of time to first flare during the 52-week treatment period. If a patient did not report a flare in the study, then the patient was censored at the last available date during which they remained in the study. q2w, Every 2 weeks; qw, weekly; TCS, topical corticosteroids.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Based on patient self-reporting, during the 12 months before enrollment, 84% (89/106) of patients receiving dupilumab plus TCS and 77% (243/315) of patients receiving TCS alone experienced flares, and the mean numbers of flares (standard deviation) per patient were 6.2 (15.8) and 4.5 (7.5), respectively. Of patients who experienced at least 1 flare before treatment, 84% (75/89) of patients receiving dupilumab plus TCS were flare-free during the treatment period versus 57% (138/243) receiving TCS alone (P < .0001). Dupilumab prevented flares in adults with moderate to severe AD, despite high initial disease burden. Even with optimal TCS use, patients receiving TCS alone were 4.5 times more likely to experience a flare compared with patients treated with dupilumab plus TCS (annualized rate ratio: 0.77 vs 0.17). Reducing the likelihood of disruptive and costly flares with long-term AD disease control is an important treatment goal that reduces patient burden and risk of inappropriate short-term AD management with systemic corticosteroids.1Sidbury R. Tom W.L. Bergman J.N. et al.Guidelines of care for the management of atopic dermatitis: section 4. Prevention of disease flares and use of adjunctive therapies and approaches.J Am Acad Dermatol. 2014; 71: 1218-1233Abstract Full Text Full Text PDF PubMed Scopus (201) Google Scholar,4Wollenberg A. Barbarot S. Bieber T. et al.Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part II.J Eur Acad Dermatol Venereol. 2018; 32: 850-878Crossref PubMed Scopus (316) Google Scholar Strengths of this analysis include the 52-week treatment duration in a large international population with moderate to severe AD and the randomized, double-blind, placebo-controlled study design. Limitations include potential recall bias in patient-reported number of flares before treatment and the fact that these results cannot be directly compared with other reports of flare prevention because of differing definitions of flare, duration of treatment, and patient baseline disease severity. Dupilumab prevents flares in adults with moderate to severe AD by providing continuous, long-term disease control. Flare prevention is an important and tangible goal of AD treatment that can inform discussions between health care providers and patients to ensure compliance and continuity in treatment. Medical writing and editorial assistance was provided by Carolyn Ellenberger, PhD, of Excerpta Medica, and funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc.