Dupilumab reduces absenteeism in patients with moderate to severe atopic dermatitis: Pooled results from the LIBERTY AD SOLO clinical trials
Authors: Marjolein de Bruin-Weller, Eric L. Simpson, Michael Cork, Zhen Chen, Jerome Msihid, Christine Taniou, Laurent Eckert, Abhijit Gadkari, Gaëlle Bégo-Le Bagousse
Journal: Journal of the American Academy of Dermatology (2020)

To the Editor: Moderate to severe atopic dermatitis (AD) negatively affects daily functioning, quality of life (QoL), and work productivity,1Eckert L. Gupta S. Amand C. Gadkari A. Mahajan P. Gelfand J.M. 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.J Am Acad Dermatol. 2017; 77: 274-279Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar more so for patients with inadequate symptom control.2Ariëns L.F.M. van Nimwegen K.J.M. Shams M. et al.Economic burden of adult patients with moderate to severe atopic dermatitis indicated for systemic treatment.Acta Derm Venereol. 2019; 99: 762-768Crossref PubMed Scopus (33) Google Scholar The SOLO 1 and 2 phase 3 clinical trials showed that dupilumab versus placebo significantly improved signs, symptoms, and QoL in patients with moderate to severe AD, with an acceptable safety profile.3Simpson E.L. Bieber T. Guttman-Yassky E. et al.Two phase 3 trials of dupilumab versus placebo in atopic dermatitis.N Engl J Med. 2016; 375: 2335-2348Crossref PubMed Scopus (1106) Google Scholar This study evaluated the impact of dupilumab on work/school productivity using a pooled analysis of the SOLO trials. The designs and primary findings from the SOLO trials have been reported previously.3Simpson E.L. Bieber T. Guttman-Yassky E. et al.Two phase 3 trials of dupilumab versus placebo in atopic dermatitis.N Engl J Med. 2016; 375: 2335-2348Crossref PubMed Scopus (1106) Google Scholar Adults with moderate to severe AD inadequately controlled by topical treatments received dupilumab (300 mg subcutaneously weekly or every 2 weeks) or placebo (subcutaneously weekly) over 16 weeks. We evaluated the mean number of missed days from work/school (absenteeism) and related costs in patients reporting full-time employment or school (≥4 days/week) and in patient subgroups categorized by baseline symptom severity, including Investigator's Global Assessment of 3 or 4, Peak Pruritus Numerical Rating Scale score of less than 7 or 7 or greater, and Dermatology Life Quality Index of less than or equal to 10 or greater than 10. Duration-adjusted annualized absenteeism rate at week 16 was estimated using Poisson regression with treatment, region, and baseline Investigator's Global Assessment strata as fixed factors and the log value of assessment days up to weeks 4, 8, 12, or 16 as offset variables. Annual productivity costs for a hypothetical cohort of 10,000 treated patients were calculated using daily labor or employee compensation costs (2018 European Union4Eurostat Statistics ExplainedEstimated hourly labour costs in the European Union.https://ec.europa.eu/eurostat/statistics-explained/index.php/Hourly_labour_costsDate accessed: October 22, 2019Google Scholar and US5US Bureau of Labor StatisticsEmployer costs for employee compensation (June 2018).https://www.bls.gov/news.release/pdf/ecec.pdfDate accessed: October 24, 2019Google Scholar rates). Most (72%) SOLO participants reported full-time work/school commitments, with similar baseline characteristics among groups (Table I). Absenteeism rates first collected at week 4 showed a difference between dupilumab and placebo groups (mean [standard error] missed days per patient-year: placebo, 12.1 [0.76]; dupilumab every 2 weeks, 5.4 [0.49]; dupilumab every week, 7.0 [0.55]). Annualized absenteeism rates by week 16 were significantly lower with dupilumab (Table II), with 5.6 (every 2 weeks) and 4.4 (every week) fewer missed days per patient-year versus placebo. This finding persisted in analyzed subgroups, with greater reductions in missed days among those with greater baseline AD severity (Table II). Reduced absenteeism resulted in lower productivity costs with dupilumab. Annual productivity costs avoided for the hypothetical cohort (based on annualized reduction of 5.6 days per patient-year with dupilumab every 2 weeks) were US$16.2 million (United States), €15.3 million (Germany), €14.1 million (France), €12.6 million (Italy), £10.1 million (United Kingdom), and €9.5 million (Spain).Table IBaseline characteristics of SOLO participants with full-time work/school commitments (full analytic sample)Baseline characteristicPlacebo (n = 319)Dupilumab 300 mg every 2 weeks (n = 332)Dupilumab 300 mg every week (n = 346)Age, y, median (Q1-Q3), range35 (26-46), 18-6435 (26-44), 18-7736 (26-47), 18-80Male sex, n (%)185 (58)206 (62)228 (66)BMI, kg/m2, median (Q1-Q3)25.1 (22.6-29.0)25.2 (22.7-28.7)25.3 (22.1-28.7)Duration of AD, y, median (Q1-Q3)27 (19-38)26 (18-38)25 (17-37)Total EASI, median (Q1-Q3)29 (22-42)29 (21-40)29 (22-43)IGA score, n (%) 3 (moderate)173 (54.2)174 (52.4)180 (52.0) 4 (severe)146 (45.8)158 (47.6)166 (48.0)Weekly averaged Peak Pruritus NRS score, median (Q1-Q3)7.7 (6.4-8.7)7.7 (6.3-8.8)7.6 (6.3-8.6)DLQI, median (Q1-Q3)14 (8-20)14 (9-20)15 (9-21)AD, Atopic dermatitis; BMI, body mass index; DLQI, Dermatology Life Quality Index; EASI, Eczema Area and Severity Index; IGA, Investigator's Global Assessment; NRS, Numerical Rating Scale; Q1, quartile 1; Q3, quartile 3. Open table in a new tab Table IIDuration-adjusted annualized absenteeism rate∗Estimated using Poisson regression with treatment, region, and baseline IGA strata as fixed factors and the log value of assessment days up to weeks 4, 8, 12, or 16 used as offset variables. per patient-year by baseline disease severity at week 16PlaceboDupilumab 300 mg every 2 weeksDupilumab 300 mg every weekFull analytic sample n319332346 Absenteeism rate, days per patient-year (SE)9.1 (0.34)3.5 (0.20)†P < .0001 versus placebo.4.7 (0.23)†P < .0001 versus placebo. 95% CI8.4-9.83.1-3.94.3-5.2IGA score of 3 n173174180 Absenteeism rate, days per patient-year (SE)6.4 (0.36)3.5 (0.26)†P < .0001 versus placebo.3.6 (0.27)†P < .0001 versus placebo. 95% CI5.7-7.13.0-4.03.1-4.1IGA score of 4 n146158166 Absenteeism rate, days per patient-year (SE)11.3 (0.55)3.2 (0.28)†P < .0001 versus placebo.5.7 (0.37)†P < .0001 versus placebo. 95% CI10.2-12.42.6-3.75.0-6.4Peak pruritus NRS of <7 n100112114 Absenteeism rate, days per patient-year (SE)5.0 (0.46)1.3 (0.20)†P < .0001 versus placebo.3.2 (0.32)‡P < .01 versus placebo. 95% CI4.1-6.00.9-1.72.5-3.8Peak pruritus NRS of ≥7 n219219230 Absenteeism rate, days per patient-year (SE)11.0 (0.44)4.8 (0.29)†P < .0001 versus placebo.5.7 (0.31)†P < .0001 versus placebo. 95% CI10.1-11.84.2-5.45.1-6.3DLQI of ≤10 n112108111 Absenteeism rate, days per patient-year (SE)1.7 (0.26)0.6 (0.14)†P < .0001 versus placebo.0.9 (0.18)‡P < .01 versus placebo. 95% CI1.2-2.20.3-0.80.5-1.2DLQI of >10 n207224235 Absenteeism rate, days per patient-year (SE)13.0 (0.49)5.0 (0.29)†P < .0001 versus placebo.6.5 (0.33)†P < .0001 versus placebo. 95% CI12.0-13.94.4-5.55.9-7.2Higher scores indicate worse signs (IGA), symptoms (Peak Pruritus NRS), and negative impact on quality of life (DLQI).CI, Confidence interval; DLQI, Dermatology Life Quality Index; IGA, Investigator's Global Assessment; NRS, Numerical Rating Scale; SE, standard error.∗ Estimated using Poisson regression with treatment, region, and baseline IGA strata as fixed factors and the log value of assessment days up to weeks 4, 8, 12, or 16 used as offset variables.† P < .0001 versus placebo.‡ P < .01 versus placebo. Open table in a new tab AD, Atopic dermatitis; BMI, body mass index; DLQI, Dermatology Life Quality Index; EASI, Eczema Area and Severity Index; IGA, Investigator's Global Assessment; NRS, Numerical Rating Scale; Q1, quartile 1; Q3, quartile 3. Higher scores indicate worse signs (IGA), symptoms (Peak Pruritus NRS), and negative impact on quality of life (DLQI). CI, Confidence interval; DLQI, Dermatology Life Quality Index; IGA, Investigator's Global Assessment; NRS, Numerical Rating Scale; SE, standard error. Dupilumab, thus, provided significant reductions in work/school absenteeism with associated cost savings versus placebo. Initial absenteeism and annualized reductions were greater with more severe AD and worse QoL at baseline. Our findings may be different from a real-world population because of the controlled nature of clinical trials. The 16-week duration-adjusted analysis was extrapolated to annual estimates; the effect of long-term treatment would require further investigation. There was no baseline assessment before treatment administration, with absenteeism rates first being collected at week 4; nonetheless, subsequent productivity outcomes were markedly different. Absenteeism rates were pooled across work/school settings and countries, with inherent variability that may affect generalizability. The productivity burden of AD on patients with inadequately controlled disease is substantial but may be ameliorated with dupilumab treatment. The authors would like to thank Qiuyue Chen for contributions to this work. Medical writing/editorial assistance was provided by Grace Richmond, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc.