BackgroundDupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhibits signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be important drivers of atopic or allergic diseases such as atopic dermatitis. MethodsIn two randomized, placebo-controlled, phase 3 trials of identical design (SOLO 1 and SOLO 2), we enrolled adults with moderate-to-severe atopic dermatitis whose disease was inadequately controlled by topical treatment. Patients were randomly assigned in a 1:1:1 ratio to receive, for 16 weeks, subcutaneous dupilumab (300 mg) or placebo weekly or the same dose of dupilumab every other week alternating with placebo. The primary outcome was the proportion of patients who had both a score of 0 or 1 (clear or almost clear) on the Investigator’s Global Assessment and a reduction of 2 points or more in that score from baseline at week 16. ResultsWe enrolled 671 patients in SOLO 1 and 708 in SOLO 2. In SOLO 1, the primary outcome occurred in 85 patients (38%) who...

/pdf/two-phase-3-trials-of-dupilumab-versus-placebo-in-atopic-3ugvfa0rqy.pdf

Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis

BACKGROUND Dupilumab, a fully human monoclonal antibody that blocks interleukin-4 and interleukin-13, has shown efficacy in patients with asthma and elevated eosinophil levels. The blockade by dupilumab of these key drivers of type 2 helper T-cell (Th2)–mediated inflammation could help in the treatment of related diseases, including atopic dermatitis. METHODS We performed randomized, double-blind, placebo-controlled trials involving adults who had moderate-to-severe atopic dermatitis despite treatment with topical glucocorticoids and calcineurin inhibitors. Dupilumab was evaluated as monotherapy in two 4-week trials and in one 12-week trial and in combination with topical glucocorticoids in another 4-week study. End points included the Eczema Area and Severity Index (EASI) score, the investigator’s global assessment score, pruritus, safety assessments, serum biomarker levels, and disease transcriptome. RESULTS In the 4-week monotherapy studies, dupilumab resulted in rapid and dose-dependent improvements in clinical indexes, biomarker levels, and the transcriptome. The results of the 12-week study of dupilumab monotherapy reproduced and extended the 4-week findings: 85% of patients in the dupilumab group, as compared with 35% of those in the placebo group, had a 50% reduction in the EASI score (EASI-50, with higher scores in the EASI indicating greater severity of eczema) (P<0.001); 40% of patients in the dupilumab group, as compared with 7% in the placebo group, had a score of 0 to 1 (indicating clearing or near-clearing of skin lesions) on the investigator’s global assessment (P<0.001); and pruritus scores decreased (indicating a reduction in itch) by 55.7% in the dupilumab group versus 15.1% in the placebo group (P<0.001). In the combination study, 100% of the patients in the dupilumab group, as compared with 50% of those who received topical glucocorticoids with placebo injection, met the criterion for EASI-50 (P = 0.002), despite the fact that patients who received dupilumab plus glucocorticoids used less than half the amount of topical glucocorticoids used by those who received placebo plus the topical medication (P = 0.16). Adverse events, such as skin infection, occurred more frequently with placebo; nasopharyngitis and headache were the most frequent adverse events with dupilumab. CONCLUSIONS Patients treated with dupilumab had marked and rapid improvement in all the evaluated measures of atopic dermatitis disease activity. Side-effect profiles were not doselimiting. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov numbers, NCT01259323, NCT01385657, NCT01639040, and NCT01548404.)

Dupilumab treatment in adults with moderate-to-severe atopic dermatitis.

Atopic dermatitis is a common and chronic, pruritic inflammatory skin condition that can affect all age groups. This evidence-based guideline addresses important clinical questions that arise in its management. In this second of 4 sections, treatment of atopic dermatitis with nonpharmacologic interventions and pharmacologic topical therapies are reviewed. Where possible, suggestions on dosing and monitoring are given based on available evidence.

https://www.jaad.org/article/S0190-9622(14)01257-2/pdf

Guidelines of care for the management of atopic dermatitis: Section 2. Management and treatment of atopic dermatitis with topical therapies

Atopic dermatitis (AD) is a chronic, pruritic, inflammatory dermatosis that affects up to 25% of children and 2% to 3% of adults. This guideline addresses important clinical questions that arise in the management and care of AD, providing updated and expanded recommendations based on the available evidence. In this first of 4 sections, methods for the diagnosis and monitoring of disease, outcomes measures for assessment, and common clinical associations that affect patients with AD are discussed. Known risk factors for the development of disease are also reviewed.

http://blackbook.com.br/wp-content/uploads/2014/02/OK-aad-2012-atopic-dermatitis-guideline-part-1-article-in-press.pdf

Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis.

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

The existing evidence for treatment of atopic eczema (atopic dermatitis, AE) is evaluated using the national standard Appraisal of Guidelines Research and Evaluation. The consensus process consisted of a nominal group process and a DELPHI procedure. Management of AE must consider the individual symptomatic variability of the disease. Basic therapy is focused on hydrating topical treatment, and avoidance of specific and unspecific provocation factors. Anti-inflammatory treatment based on topical glucocorticosteroids and topical calcineurin inhibitors (TCI) is used for exacerbation management and more recently for proactive therapy in selected cases. Topical corticosteroids remain the mainstay of therapy, but the TCI tacrolimus and pimecrolimus are preferred in certain locations. Systemic immune-suppressive treatment is an option for severe refractory cases. Microbial colonization and superinfection may induce disease exacerbation and can justify additional antimicrobial treatment. Adjuvant therapy includes UV irradiation preferably with UVA1 wavelength or UVB 311 nm. Dietary recommendations should be specific and given only in diagnosed individual food allergy. Allergen-specific immunotherapy to aeroallergens may be useful in selected cases. Stress-induced exacerbations may make psychosomatic counselling recommendable. 'Eczema school' educational programs have been proven to be helpful. Pruritus is targeted with the majority of the recommended therapies, but some patients need additional antipruritic therapies.

https://www.onlinelibrary.wiley.com/doi/epdf/10.1111/j.1468-3083.2012.04635.x

S. Szalai

Papers

Guidelines for treatment of atopic eczema (atopic dermatitis) part I.