Long-Term Effectiveness of Dupilumab in Patients with Atopic Dermatitis: Results up to 3 Years from the RELIEVE-AD Study.

INTRODUCTION: Atopic dermatitis (AD) can require long-term therapy. Few real-world studies have evaluated long-term effectiveness from the patients' perspective. The aim of this study was to evaluate patient-reported outcomes (PROs) during long-term dupilumab treatment. METHODS: Adults with moderate-to-severe AD who initiated dupilumab through the US manufacturer patient support program and participated in RELIEVE-AD (a prospective patient survey study with a 12-month follow-up) were recontacted 30-36 months post-initiation regardless of current dupilumab use. The online questionnaire consisted of PROs, including the Atopic Dermatitis Control Tool (ADCT), use of concomitant AD therapies, satisfaction with current therapy, global change in itch relative to before dupilumab initiation, non-itch skin symptoms (skin pain/soreness, hot/burning feeling, and sensitivity to touch), flares, Dermatology Life Quality Index, sleep problems, and the AD-specific Work Productivity and Activity Impairment Questionnaire. RESULTS: Of 698 patients who initiated dupilumab (baseline) and were recontacted, 425 completed the 30-36-month survey. Significant reductions from baseline were reported in concomitant AD therapy use (P < 0.05); 54.4% reported not using other AD medications vs. 12.8% at baseline. At 30-36 months, all results (non-itch skin symptoms, flares, sleep problems, health-related quality of life work/activity impairment, disease control, and treatment satisfaction) were similar to or incrementally better than the 12-month timepoint, with significant improvements vs. baseline (P < 0.001). Global change in itch was reported as "very much better" by 75.3% of respondents. Adequate disease control (score < 7 on ADCT) was reported by 80.7% of respondents, and 86.8% were satisfied with the treatment. CONCLUSIONS: In clinical practice settings, patient-reported benefits of dupilumab were maintained in survey respondents during long-term treatment up to 36 months while the use of concomitant AD therapies reduced.

Atopic dermatitis (also known as eczema) is a chronic skin disease that can have a profoundly negative effect on patients' quality of life. To control disease symptoms, patients often need long-term treatment. Dupilumab is a treatment that has shown benefits in adults with moderate-to-severe atopic dermatitis (AD) when used in long-term (under 4 years) clinical trials; however, few studies have evaluated patients' experiences of long-term dupilumab treatment outside of a clinical trial setting. This study was conducted to do so: 425 adults with moderate-to-severe AD who received dupilumab through a US manufacturer patient support program filled in an online questionnaire 30­36 months after starting treatment. The questionnaire included items on use of additional AD therapies, AD symptoms, quality of life, disease control, and satisfaction with treatment. Patients' responses showed that, at 30­36 months after starting dupilumab treatment, 54% of patients reported not using any other medications for AD vs. 13% of patients when starting dupilumab treatment. In addition, since starting dupilumab, 75% of patients reported one of the most burdensome AD symptoms, itch, as being "very much better" vs. before starting treatment; 81% reported control of AD symptoms; 85% reported a meaningful improvement in quality of life; and 76% were "extremely" or "very" satisfied with the treatment. In summary, this study showed that long-term dupilumab treatment provides continued improvement in symptoms, treatment satisfaction, disease control, and quality of life in adults with moderate-to-severe AD while reducing the need for other AD treatments. Video abstract: How do patients with atopic dermatitis perceive long-term dupilumab treatment in the real world? (MP4 31888 kb).

Impact of the Family and Household Environment on Pediatric Atopic Dermatitis in Japan.

Pediatric atopic dermatitis (AD) can negatively impact the family quality of life (QoL). We report data from the real-world Epidemiology of Children with Atopic Dermatitis Reporting on their Experience (EPI-CARE) study in Japanese pediatric patients, focusing on disease impact on family QoL. Children and adolescents aged 6 months to <18 years completed an online survey between September 2018-December 2019. The impact of disease severity on family QoL and its effect on parents' time were assessed using the dermatitis family impact (DFI) questionnaire. The impact of a family history of allergic conditions, current residency, second-hand smoke exposure, and household pets on AD prevalence and severity was also assessed. Family QoL decreased as AD severity increased, particularly in families with children aged <6 years; but had the greatest impact on sleep and tiredness in families with children aged <12 years. Parents spent at least 4.6 h/week caring for children <6 years, including those with mild symptoms. Most children (>80%) had a family history of allergic conditions; AD prevalence was increased in those exposed to second-hand smoke or household pets. This study demonstrated that pediatric AD in Japanese individuals has negative impacts on family QoL and that family and household environments can influence pediatric AD prevalence.

Efficacy and Safety of Dupilumab Maintained in Adults ≥ 60 Years of Age with Moderate-to-Severe Atopic Dermatitis: Analysis of Pooled Data from Four Randomized Clinical Trials.

BACKGROUND: Adults aged ≥ 60 years are often underrepresented in atopic dermatitis (AD) clinical trials; age-related comorbidities may impact treatment efficacy and safety. OBJECTIVE: The aim was to report dupilumab efficacy and safety in patients aged ≥ 60 years with moderate-to-severe AD. METHODS: Data were pooled from four randomized, placebo-controlled dupilumab trials of patients with moderate-to-severe AD (LIBERTY AD SOLO 1 and 2, LIBERTY AD CAFÉ, and LIBERTY AD CHRONOS) and stratified by age (< 60 [N = 2261] and ≥ 60 [N = 183] years). Patients received dupilumab 300 mg every week (qw) or every 2 weeks (q2w), or placebo with/without topical corticosteroids. Post hoc efficacy at week 16 was examined using broad categorical and continuous assessments of skin lesions, symptoms, biomarkers, and quality of life. Safety was also assessed. RESULTS: In the ≥ 60-year-old group at week 16, a greater proportion of dupilumab-treated patients achieved an Investigator's Global Assessment score of 0/1 (q2w: 44.4%; qw: 39.7%) and 75% improvement in Eczema Area and Severity Index (63.0%; 61.6%) versus placebo (7.1% and 14.3%, respectively; P < 0.0001). Type 2 inflammation biomarkers (immunoglobulin E and thymus and activation-regulated chemokine) were also significantly reduced in dupilumab- versus placebo-treated patients (P < 0.01). Results were similar in the < 60-year-old group. The exposure-adjusted incidences of adverse events in dupilumab-treated patients were generally similar to those receiving placebo, with numerically fewer treatment-emergent adverse events in the dupilumab-treated ≥ 60-year-old group versus placebo. LIMITATIONS: There were fewer patients in the ≥ 60-year-old group; post hoc analyses. CONCLUSION: Dupilumab improved AD signs and symptoms in patients aged ≥ 60 years; results were comparable to those in patients aged < 60 years. Safety was consistent with the known dupilumab safety profile. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02277743, NCT02277769, NCT02755649, NCT02260986. Does dupilumab benefit adults aged 60 years and older with moderate-to-severe atopic dermatitis?(MP4 20,787 KB).

Dupilumab Treatment Reduces Hospitalizations in Adults With Moderate-to-Severe Atopic Dermatitis.

BACKGROUND: Refractory disease, flares, or infections in atopic dermatitis (AD) can lead to hospitalizations. OBJECTIVE: To compare hospitalization rates among adults with moderate-to-severe AD treated with dupilumab versus control. METHODS: Data from 7 randomized, placebo-controlled trials of dupilumab (300 mg every 2 weeks [q2w] and/or weekly [qw]; with or without topical corticosteroids) were analyzed. RESULTS: Patients in the dupilumab 300 mg q2w, qw, and combined dupilumab (q2w and qw; n = 1,841) groups compared with patients in the control group (n = 1,091) had lower rates of all-cause hospitalizations (5.8, 2.7, and 3.8 events, respectively, vs 9.0 events per 100 patient-years [PY]; all P < .05 [49%, 71%, and 62% risk reduction, respectively]); AD-related hospitalizations (2.0, 0.4, 1.0 events vs 4.1 events per 100 PY; P < .05 for qw and dupilumab combined [91% and 79% risk reduction, respectively]); as well as reduced overall duration of AD-related hospitalization (10.9, 7.3, and 8.6 d vs 38.9 d per 100 PY). CONCLUSIONS: Among adults with moderate-to-severe AD, treatment with dupilumab versus control was associated with significant reductions in all-cause and AD-related hospitalization rates, and shorter duration of AD-related hospitalization.

Dupilumab Provides Rapid and Sustained Clinically Meaningful Responses in Adults with Moderate-to-severe Atopic Dermatitis.

Optimal management of atopic dermatitis requires a comprehensive assessment of response to treatment in order to inform therapeutic decisions. In a real-world setting, successful response to atopic dermatitis treatment is measured by sustained improvements in signs, symptoms, and quality of life. Post-hoc analyses of a 1-year, randomized, double-blinded, placebo- controlled trial (NCT02260986) of dupilumab with concomitant topical corticosteroids in 421 adults with moderate-to-severe atopic dermatitis (of whom 315/106 received placebo/dupilumab (of whom 315 received placebo and 106 received dupilumab) was performed to assess the proportion of responders to dupilumab through a multidimensional composite endpoint. At 6-months, 80.2% of dupilumab-treated vs 40.0% placebo patients (p < 0.0001) achieved improvement in signs (Eczema Area and Severity Index ≤ 7), symptoms (worst itch score ≤ 4), or quality of life (Dermatology Life Quality Index ≤5), representative of minimal/clear atopic dermatitis. All 3 endpoints, indicative of no/minimal atopic dermatitis, were achieved by 44.3% of dupilumab-treated vs 10.2% placebo patients (p < 0.0001) and sustained through 1 year. Dupilumab treatment provided sustained clinically meaningful improvement in signs, symptoms, and quality of life in adults with moderate-to-severe atopic dermatitis.

Health utility estimation in children and adolescents: a review of health technology assessments.

Objective: Health utility estimates for children and adolescents are critical for cost-utility analyses informing health technology assessment (HTA) authorities' decisions governing access to pediatric treatments. However, in a recent review, only 29% of published pediatric cost-utility models used a utility measure validated for children. We examined utility estimates used in pediatric HTAs.Methods: A targeted review of pediatric HTAs was performed, focusing on agencies reporting utility estimate sources and methods.Results: Searches identified 11 HTAs in pediatric indications and five in mixed populations with separate analyses for adults and children. Among 13 appraisals reporting methodological detail, five used pediatric utility estimates (based on the Health Utilities Index [HUI], n = 3; Atopic Dermatitis Quality of Life [ADQoL], n = 1; or mapping, n = 1). Issues were identified with mapping, use of adult data for some health states, and assumptions about ADQoL responses. In the remaining eight appraisals, adult utility estimates were applied. Caregiver utility was included in two of 16 appraisals.Conclusions: Only 38% of pediatric HTAs reviewed used pediatric utility estimates, and HTA authorities raised concerns about these data in many cases; only 12% of HTAs included caregiver utility. Although several preference-based utility measures are available for pediatric populations, limited data and guidance on selection of measures are available. When estimating pediatric utility weights, alternative measures should be reviewed for suitability given the model population and health condition. Pediatric and adult utility estimates should be applied appropriately as patients age over time, and caregiver and/or family member utility should be included, where relevant. Gaps exist in utility measures for children aged <4 years and caregivers.

Dupilumab Versus Cyclosporine for the Treatment of Moderate-to-Severe Atopic Dermatitis in Adults: Indirect Comparison Using the Eczema Area and Severity Index.

Dupilumab is approved for uncontrolled moderate-to-severe atopic dermatitis (AD); cyclosporine is approved for severe AD for ≤ 1 year. The efficacy/effectiveness of these treat-ments was compared indirectly. Regression models used pooled patient-level data to estimate response (Eczema Area and Severity Index (EASI) EASI-50/EASI-75 at weeks 12-16 and 24-30) to dupilumab 300 mg every 2 weeks (CHRONOS [NCT02260986]) or cyclosporine (University Medical Center). Models were adjusted for sex, baseline EASI, and thymus and activation-regulated chemokine level. A total of 106 patients received dupilumab (+ topical cortico-steroids; + TCS), and 57 received cyclosporine (+ TCS). Among University Medical Center patients, estimated EASI-50 responders were, dupilumab vs. cyclosporine, 91% vs. 77% (p = 0.038; weeks 12-16), and 96% vs. 67% (p < 0.0001; weeks 24-30); EASI-75 responders were 78% vs. 56% (p = 0.016; weeks 12-16) and 80% vs. 47% (p <0.001; weeks 24-30). Among CHRONOS patients, estimated EASI-50 responders were 90% vs. 74% (p <0.038; weeks 12-16) and 92% vs. 53% (p < 0.0001; weeks 24-30); EASI-75 responders were 75% vs. 52% (p = 0.016; weeks 12-16) and 74% vs. 40% (p <0.001; weeks 24-30), respectively. These results suggest a higher relative efficacy of dupilumab vs. cyclosporine.

Health Care Resource Utilization and Costs Among Adults with Atopic Dermatitis in the United States: A Claims-Based Analysis.

BACKGROUND: Data on health care resource utilization (HCRU) and costs for patients with atopic dermatitis (AD) are lacking. OBJECTIVE: The objective of this study was to determine HCRU and costs associated with AD in US adults. METHODS: This retrospective study identified patients with AD from the Truven Health Marketscan Commercial Claims and Encounters database during 2013 based on ≥2 claims with International Classification of Diseases, Ninth Revision code 691.8 (n = 10,533; first claim = index event); 1-year continuous enrollment before and after index was required. Patients were age- and gender-matched in a 1:3 ratio to controls without AD (n = 31,599). Patients with AD were further categorized into 2 groups, with treatment regimens as surrogates for increasing disease severity: claim for phototherapy or systemic immunomodulatory agents (more severe) or no claim for either (less severe). Incremental differences in resource use and costs were evaluated using multivariate analysis. RESULTS: AD was associated with higher utilization and costs across resource categories (all P < .0001); adjusted total incremental annual costs were $3,302. Resource utilization and costs were higher in the more severe group, with adjusted total incremental annual costs of $4,463. CONCLUSION: AD is associated with significant incremental health care utilization and costs, which are higher in patients with more severe disease.

Economic Evaluation of Dupilumab for the Treatment of Moderate-to-Severe Atopic Dermatitis in Adults.

INTRODUCTION: Dupilumab 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. METHODS: A 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$100,000 and $150,000 per quality-adjusted life-year (QALY) gained. RESULTS: In the base case, the annual maintenance price for dupilumab therapy to be considered cost-effective would be $28,770 at a $100,000 per QALY gained threshold, and $39,940 at a $150,000 threshold. Results were generally robust to parameter variations in one-way and probabilistic sensitivity analyses. CONCLUSION: Dupilumab q2w compared with SC is cost-effective for the treatment of moderate-to-severe AD in US adults at an annual price of maintenance therapy in the range of $29,000-$40,000 at the $100,000-$150,000 per QALY thresholds. FUNDING: Sanofi and Regeneron Pharmaceuticals, Inc.

Teriflunomide reduces relapse-related neurological sequelae, hospitalizations and steroid use.

Multiple sclerosis (MS) relapses impose a substantial clinical and economic burden. Teriflunomide is a new oral disease-modifying therapy approved for the treatment of relapsing MS. We evaluated the effects of teriflunomide treatment on relapse-related neurological sequelae and healthcare resource use in a post hoc analysis of the Phase III TEMSO study. Confirmed relapses associated with neurological sequelae [defined by an increase in Expanded Disability Status Scale/Functional System (sequelae-EDSS/FS) ≥ 30 days post relapse or by the investigator (sequelae-investigator)] were analyzed in the modified intention-to-treat population (n = 1086). Relapses requiring hospitalization or intravenous (IV) corticosteroids, all hospitalizations, emergency medical facility visits (EMFV), and hospitalized nights for relapse were also assessed. Annualized rates were derived using a Poisson model with treatment, baseline EDSS strata, and region as covariates. Risks of sequelae and hospitalization per relapse were calculated as percentages and groups were compared with a χ(2) test. Compared with placebo, teriflunomide reduced annualized rates of relapses with sequelae-EDSS/FS [7 mg by 32 % (p = 0.0019); 14 mg by 36 % (p = 0.0011)] and sequelae-investigator [25 % (p = 0.071); 53 % (p < 0.0001)], relapses leading to hospitalization [36 % (p = 0.015); 59 % (p < 0.0001)], and relapses requiring IV corticosteroids [29 % (p = 0.001); 34 % (p = 0.0003)]. Teriflunomide-treated patients spent fewer nights in hospital for relapse (p < 0.01). Teriflunomide 14 mg also decreased annualized rates of all hospitalizations (p = 0.01) and EMFV (p = 0.004). The impact of teriflunomide on relapse-related neurological sequelae and relapses requiring healthcare resources may translate into reduced healthcare costs.

Cost-effectiveness analysis of dronedarone versus other anti-arrhythmic drugs for the treatment of atrial fibrillation--results for Canada, Italy, Sweden and Switzerland.

The ATHENA clinical trial enrolled 4,628 patients in 37 countries and evaluated the efficacy of dronedarone 400 mg twice daily versus placebo for the prevention of cardiovascular hospitalisation or death from any cause in patients with paroxysmal or persistent atrial fibrillation or atrial flutter. The trial showed a statistically significant 24% reduction in the primary endpoint cardiovascular hospitalisations or all-cause death. In the current paper, parameters that drive the cost-effectiveness of dronedarone on top of standard therapy versus likely comparators, i.e. amiodarone, sotalol and flecainide, were investigated by means of a health economic model based on the ATHENA clinical trial. Dronedarone is cost-effective, and ICERs are low versus amiodarone with €5,340; €4,620; €3,850 and €5,630 per QALY gained for Canada, Italy, Sweden and Switzerland, respectively. The most significant driving factor for the cost-effectiveness of dronedarone is the increased survival rate for patients on dronedarone.