Abhijit Gadkari

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

BACKGROUND Dupilumab (an anti-interleukin-4-receptor-α monoclonal antibody) blocks signalling of interleukin 4 and interleukin 13, type 2/Th2 cytokines implicated in numerous allergic diseases ranging from asthma to atopic dermatitis. Previous 16-week monotherapy studies showed that dupilumab substantially improved signs and symptoms of moderate-to-severe atopic dermatitis with acceptable safety, validating the crucial role of interleukin 4 and interleukin 13 in atopic dermatitis pathogenesis. We aimed to evaluate the long-term efficacy and safety of dupilumab with medium-potency topical corticosteroids versus placebo with topical corticosteroids in adults with moderate-to-severe atopic dermatitis. METHODS In this 1-year, randomised, double-blinded, placebo-controlled, phase 3 study (LIBERTY AD CHRONOS), adults with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids were enrolled at 161 hospitals, clinics, and academic institutions in 14 countries in Europe, Asia-Pacific, and North America. Patients were randomly assigned (3:1:3) to subcutaneous dupilumab 300 mg once weekly (qw), dupilumab 300 mg every 2 weeks (q2w), or placebo via a central interactive voice/web response system, stratified by severity and global region. All three groups were given concomitant topical corticosteroids with or without topical calcineurin inhibitors where inadvisable for topical corticosteroids. Topical corticosteroids could be tapered, stopped, or restarted on the basis of disease activity. Coprimary endpoints were patients (%) achieving Investigators Global Assessment (IGA) 0/1 and 2-point or higher improvement from baseline, and Eczema Area and Severity Index 75% improvement from baseline (EASI-75) at week 16. Week 16 efficacy and week 52 safety analyses included all randomised patients; week 52 efficacy included patients who completed treatment by US regulatory submission cutoff. This study is registered with ClinicalTrials.gov, NCT02260986. FINDINGS Between Oct 3, 2014, and July 31, 2015, 740 patients were enrolled: 319 were randomly assigned to dupilumab qw plus topical corticosteroids, 106 to dupilumab q2w plus topical corticosteroids, and 315 to placebo plus topical corticosteroids. 623 (270, 89, and 264, respectively) were evaluable for week 52 efficacy. At week 16, more patients who received dupilumab plus topical corticosteroids achieved the coprimary endpoints of IGA 0/1 (39% [125 patients] who received dupilumab plus topical corticosteroids qw and 39% [41 patients] who received dupilumab q2w plus topical corticosteroids vs 12% [39 patients] who received placebo plus topical corticosteroids; p<0·0001) and EASI-75 (64% [204] and 69% [73] vs 23% [73]; p<0·0001). Week 52 results were similar. Adverse events were reported in 261 (83%) patients who received dupilumab qw plus topical corticosteroids, 97 (88%) patients who received dupilumab q2w, and 266 (84%) patients who received placebo, and serious adverse events in nine (3%), four (4%), and 16 (5%) patients, respectively. No significant dupilumab-induced laboratory abnormalities were noted. Injection-site reactions and conjunctivitis were more common in patients treated with dupilumab plus topical corticosteroids-treated patients than in patients treated with placebo plus topical corticosteroids. INTERPRETATION Dupilumab added to standard topical corticosteroid treatment for 1 year improved atopic dermatitis signs and symptoms, with acceptable safety. FUNDING Sanofi and Regeneron Pharmaceuticals Inc.

Impact of atopic dermatitis on health-related quality of life and productivity in adults in the United States: An analysis using the National Health and Wellness Survey

Background Given its public health impact, there is need for broad and representative data on the humanistic burden of atopic dermatitis (AD). Objective To establish the humanistic burden of AD in US adults. Methods Data were from the 2013 US National Health and Wellness Survey; AD self‐reports were propensity‐matched with non‐AD controls and with psoriasis controls. Bivariate analyses were conducted on burden outcomes between the AD and control groups. Results Demographics and baseline characteristics were comparable between matched groups. Subjects with AD (n = 349) versus non‐AD controls (n = 698) had significantly higher rates of anxiety, depression, and sleep disorders (29.8%, 31.2%, and 33.2% vs 16.1%, 17.3%, and 19.2%, respectively [all P < .001]); a lower Short Form‐36 v2 mental component summary score (44.5 vs 48.0, respectively [P < .001]); a lower physical component summary score (47.6 vs 49.5, respectively [P = .004]), and lower health utilities (0.67 vs 0.72, respectively [P < .001]) in addition to a higher work absenteeism rate (9.9% vs 3.6%, respectively [P < .001]) and activity impairment rate (33.6% vs 25.2%, respectively [P < .001]). Subjects with AD and psoriasis controls (n = 260 each) showed similar impairment in health‐related quality of life and productivity. Limitations Data were self‐reported. Conclusion AD is associated with a substantial humanistic burden that is similar in magnitude to that of psoriasis, which is also recognized for its debilitating symptoms, indicating the need for more effective treatments for AD.

Dupilumab with concomitant topical corticosteroids in adult patients with atopic dermatitis who are not adequately controlled with or are intolerant to ciclosporin A, or when this treatment is medically inadvisable: a placebo-controlled, randomized phase 3 clinical trial (LIBERTY AD CAFÉ)

Atopic dermatitis is a chronic inflammatory skin disease that may require systemic therapy. Ciclosporin A (CsA) is a widely used, potent immunosuppressant but it is not effective in all patients with atopic dermatitis, and side‐effects limit its use. Dupilumab, a fully human anti‐interleukin 4 receptor‐alpha monoclonal antibody, inhibits signaling of IL‐4 and IL‐13, key drivers of Type 2/Th2‐mediated inflammation, and is approved in the U.S.A. and the European Union for the treatment of inadequately‐controlled moderate‐to‐severe atopic dermatitis in adults.

Epidemiology of atopic dermatitis in adults: Results from an international survey

There are gaps in our knowledge of the prevalence of adult atopic dermatitis (AD).

The burden of atopic dermatitis in US adults: Health care resource utilization data from the 2013 National Health and Wellness Survey

Background: There is a lack of data on the burden of atopic dermatitis (AD) in adults relative to the general population. Objective: To characterize the AD burden in adult patients relative to both matched non‐AD controls and matched patients with psoriasis in terms of comorbidities, health care resource utilization (HCRU), and costs. Methods: Adults (≥18 years) who self‐reported a diagnosis of AD or psoriasis and adult non‐AD controls were identified from the 2013 US National Health and Wellness Survey. Patients with AD were propensity score–matched with non‐AD controls and patients with psoriasis on demographic variables. Patient‐reported outcomes were analyzed between matched cohorts. Results: Patients with AD had a significantly greater risk for atopic comorbidities, as well as significantly greater HCRU and total cost compared with non‐AD controls. The burden of AD was generally comparable to that of psoriasis, although patients with AD reported increased use of emergency room visits compared with patients with psoriasis. Limitations: Patient‐reported data are susceptible to recall bias and erroneous classification. Conclusions: Adult patients with AD reported a substantial disease burden, suggesting an unmet need for more effective AD treatment options.

Economic evaluation of dupilumab for the treatment of moderate-to-severe atopic dermatitis in adults

IntroductionDupilumab significantly improves signs and symptoms of atopic dermatitis (AD), including pruritus, symptoms of anxiety and depression, and health-related quality of life versus placebo in adults with moderate-to-severe AD. Since the cost-effectiveness of dupilumab has not been evaluated, the objective of this analysis was to estimate a value-based price range in which dupilumab would be considered cost-effective compared with supportive care (SC) for treatment of moderate-to-severe AD in an adult population.MethodsA health economic model was developed to evaluate from the US payer perspective the long-term costs and benefits of dupilumab treatment administered every other week (q2w). Dupilumab q2w was compared with SC; robustness of assumptions and results were tested using sensitivity and scenario analyses. Clinical data were derived from the dupilumab LIBERTY AD SOLO trials; healthcare use and cost data were from health insurance claims histories of adult patients with AD. The annual price of maintenance therapy with dupilumab to be considered cost-effective was estimated for decision thresholds of US

Extent and consequences of inadequate disease control among adults with a history of moderate to severe atopic dermatitis

100,000 and

Burden of atopic dermatitis in Japanese adults: Analysis of data from the 2013 National Health and Wellness Survey

150,000 per quality-adjusted life-year (QALY) gained.ResultsIn the base case, the annual maintenance price for dupilumab therapy to be considered cost-effective would be

Association of Inadequately Controlled Disease and Disease Severity With Patient-Reported Disease Burden in Adults With Atopic Dermatitis

28,770 at a

杜匹鲁单抗结合伴随性局部皮质类固醇治疗对环孢素A应答不充分或不耐受或者在医学上不建议采用环孢素A治疗的过敏性皮肤炎成人患者:安慰剂对照随机阶段III临床试验(LIBERTY AD CAFÉ)

100,000 per QALY gained threshold, and