Bégo-Le Bagousse, G.

Chen, Z.

Cork, M.

de Bruin-Weller, M.

Eckert, L.

Gadkari, A.

Msihid, J.

Simpson, E.L.

Taniou, C.

English

White Rose Research Online

Dupilumab reduces absenteeism in patients with moderate to severe atopic dermatitis: Pooled results from the LIBERTY AD SOLO clinical trials

This is a repository copy of Dupilumab reduces absenteeism in patients with moderate to severe atopic dermatitis: Pooled results from the LIBERTY AD SOLO clinical trials.White Rose Research Online URL for this paper:http://eprints.whiterose.ac.uk/166195/Version: Published VersionArticle:de Bruin-Weller, M., Simpson, E.L., Cork, M. orcid.org/0000-0003-4428-2428 et al. (6 moreauthors) (2020) Dupilumab reduces absenteeism in patients with moderate to severe atopic dermatitis: Pooled results from the LIBERTY AD SOLO clinical trials. Journal of the American Academy of Dermatology. ISSN 0190-9622 https://doi.org/10.1016/j.jaad.2020.05.142eprints@whiterose.ac.ukhttps://eprints.whiterose.ac.uk/Reuse This article is distributed under the terms of the Creative Commons Attribution (CC BY) licence. This licence allows you to distribute, remix, tweak, and build upon the work, even commercially, as long as you credit the authors for the original work. More information and the full terms of the licence here: https://creativecommons.org/licenses/ Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request. LETTERRESEARCH LETTERDupilumab reduces absenteeism inpatients with moderate to severeatopic dermatitis: Pooled resultsfrom the LIBERTY AD SOLO clinicaltrialsTo the Editor: Moderate to severe atopic dermatitis(AD) negatively affects daily functioning, quality oflife (QoL), and work productivity,1 more so forpatients with inadequate symptom control.2 TheSOLO 1 and 2 phase 3 clinical trials showed thatdupilumab versus placebo significantly improvedsigns, symptoms, and QoL in patients with moderateto severe AD, with an acceptable safety profile.3 Thisstudy evaluated the impact of dupilumab on work/school productivity using a pooled analysis of theSOLO trials.The designs and primary findings from the SOLOtrials have been reported previously.3 Adults withmoderate to severe AD inadequately controlled bytopical treatments received dupilumab (300 mg sub-cutaneously weekly or every 2 weeks) or placebo(subcutaneously weekly) over 16 weeks. We evalu-ated the mean number of missed days from work/school (absenteeism) and related costs in patientsreporting full-time employment or school ($4 days/week) and in patient subgroups categorized bybaseline symptom severity, including Investigator’sGlobal Assessment of 3 or 4, Peak Pruritus NumericalRating Scale score of less than 7 or 7 or greater, andDermatology Life Quality Index of less than or equalto 10 or greater than 10. Duration-adjusted annual-ized absenteeism rate at week 16 was estimatedusing Poisson regression with treatment, region, andbaseline Investigator’s Global Assessment strata asfixed factors and the log value of assessment days upto weeks 4, 8, 12, or 16 as offset variables. Annualproductivity costs for a hypothetical cohort of 10,000treated patients were calculated using daily labor oremployee compensation costs (2018 EuropeanUnion4 and US5 rates).Most (72%) SOLO participants reported full-timework/school commitments, with similar baseline char-acteristics among groups (Table I). Absenteeism ratesfirst collected at week 4 showed a difference betweendupilumab 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 everyweek, 7.0 [0.55]). Annualized absenteeism rates byweek 16 were significantly lower with dupilumab(Table II), with 5.6 (every 2 weeks) and 4.4 (everyweek) fewer missed days per patient-year versusplacebo. This finding persisted in analyzed subgroups,with greater reductions in missed days among thosewith greater baseline AD severity (Table II). ReducedTable I. Baseline characteristics of SOLO participants with full-time work/school commitments (full analyticsample)Baseline characteristic Placebo (n = 319)Dupilumab 300 mgevery 2 weeks (n = 332)Dupilumab 300 mgevery week (n = 346)Age, y, median (Q1-Q3), range 35 (26-46), 18-64 35 (26-44), 18-77 36 (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 NRSscore, 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’sGlobal Assessment; NRS, Numerical Rating Scale; Q1, quartile 1; Q3, quartile 3.ª 2020 by the American Academy of Dermatology, Inc. Published byElsevier Inc. This is an open access article under the CC BY license(http://creativecommons.org/licenses/by/4.0/).J AM ACAD DERMATOL n 2020 1absenteeism resulted in lower productivity costs withdupilumab. Annual productivity costs avoided for thehypothetical cohort (based on annualized reduction of5.6 days per patient-year with dupilumab every2 weeks) were US$16.2 million (United States), V15.3million (Germany), V14.1 million (France), V12.6million (Italy), £10.1 million (United Kingdom), andV9.5 million (Spain).Dupilumab, thus, provided significant reductionsin work/school absenteeism with associated costsavings versus placebo. Initial absenteeism andannualized reductions were greater with more se-vere AD and worse QoL at baseline.Our findings may be different from a real-worldpopulation because of the controlled nature ofclinical trials. The 16-week duration-adjusted anal-ysis was extrapolated to annual estimates; the effectof long-term treatment would require further inves-tigation. There was no baseline assessment beforetreatment administration, with absenteeism rates firstbeing collected at week 4; nonetheless, subsequentproductivity outcomes were markedly different.Absenteeism rates were pooled across work/schoolsettings and countries, with inherent variability thatmay affect generalizability.The productivity burden of AD on patientswith inadequately controlled disease is substan-tial but may be ameliorated with dupilumabtreatment.The authors would like to thank Qiuyue Chen forcontributions to this work. Medical writing/editorialassistance was provided by Grace Richmond, PhD, ofExcerpta Medica, funded by Sanofi Genzyme and Regen-eron Pharmaceuticals, Inc.Table II. Duration-adjusted annualized absenteeism rate* per patient-year by baseline disease severity atweek 16PlaceboDupilumab 300 mgevery 2 weeksDupilumab 300 mgevery weekFull analytic samplen 319 332 346Absenteeism rate, days per patient-year (SE) 9.1 (0.34) 3.5 (0.20)y 4.7 (0.23)y95% CI 8.4-9.8 3.1-3.9 4.3-5.2IGA score of 3n 173 174 180Absenteeism rate, days per patient-year (SE) 6.4 (0.36) 3.5 (0.26)y 3.6 (0.27)y95% CI 5.7-7.1 3.0-4.0 3.1-4.1IGA score of 4n 146 158 166Absenteeism rate, days per patient-year (SE) 11.3 (0.55) 3.2 (0.28)y 5.7 (0.37)y95% CI 10.2-12.4 2.6-3.7 5.0-6.4Peak pruritus NRS of\7n 100 112 114Absenteeism rate, days per patient-year (SE) 5.0 (0.46) 1.3 (0.20)y 3.2 (0.32)z95% CI 4.1-6.0 0.9-1.7 2.5-3.8Peak pruritus NRS of $7n 219 219 230Absenteeism rate, days per patient-year (SE) 11.0 (0.44) 4.8 (0.29)y 5.7 (0.31)y95% CI 10.1-11.8 4.2-5.4 5.1-6.3DLQI of #10n 112 108 111Absenteeism rate, days per patient-year (SE) 1.7 (0.26) 0.6 (0.14)y 0.9 (0.18)z95% CI 1.2-2.2 0.3-0.8 0.5-1.2DLQI of[10n 207 224 235Absenteeism rate, days per patient-year (SE) 13.0 (0.49) 5.0 (0.29)y 6.5 (0.33)y95% CI 12.0-13.9 4.4-5.5 5.9-7.2Higher 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 upto weeks 4, 8, 12, or 16 used as offset variables.yP\ .0001 versus placebo.zP\ .01 versus placebo.J AM ACAD DERMATOLn 20202 LetterMarjolein de Bruin-Weller, MD, PhD,a Eric L.Simpson, MD, MCR,b Michael Cork, BSc, MB,PhD, FRCP,c Zhen Chen, PhD, MS, MA,d JeromeMsihid, MSc,e Christine Taniou, MSc,f LaurentEckert, PhD,e Abhijit Gadkari, PhD,d and Ga€elleBego-Le Bagousse, MSceFrom the University Medical Center Utrecht,Utrecht, the Netherlandsa; Department of Derma-tology, Oregon Health & Science University,Portland, Oregonb; Sheffield DermatologyResearch, The University of Sheffield, SheffieldChildren’s Hospital, Sheffield, United Kingdomc;Regeneron Pharmaceuticals, Inc, Tarrytown,New Yorkd; Sanofi, Chilly-Mazarin, Francee;and Altran Technologies, Velizy-Villacoublay,France.fFunding sources: Supported by Sanofi and Regen-eron Pharmaceuticals, Inc.Disclosure: Dr de Bruin-Weller is a consultant/advisor for AbbVie, Eli Lilly, Pfizer, RegeneronPharmaceuticals, Inc, Sanofi Genzyme, andUCB and has received grant/research supportfrom Regeneron Pharmaceuticals and SanofiGenzyme. Dr Simpson reports grants from EliLilly, Kyowa Hakko Kirin, LEO Pharma, Merck,Pfizer, and Regeneron Pharmaceuticals Inc andpersonal fees from Dermira, Eli Lilly, Galderma,LEO Pharma, Menlo Therapeutics, Novartis,Pfizer, Regeneron Pharmaceuticals Inc, SanofiGenzyme, and Valeant. Dr Cork is an investi-gator and/or consultant for Astellas, Boots,Dermavant, Galapagos, Galderma, Hyphens,Johnson & Johnson, Kymab, LEO Pharma,L’Oreal, Menlo Therapeutics, Novartis, Oxagen,Pfizer, Procter & Gamble, Reckitt Benckiser,Regeneron Pharmaceuticals Inc, and SanofiGenzyme. Dr Chen is an employee and share-holder of Regeneron Pharmaceuticals, Inc. DrsMsihid, Eckert, and Bego-Le Bagousse are em-ployees and may hold stock and/or stock optionsin Sanofi. Dr Taniou is an employee of AltranTechnology. Dr Gadkari was a full-timeemployee of Regeneron Pharmaceuticals Incwhen this work was conducted, received salaryand bonus from Regeneron PharmaceuticalsInc, and is currently a full-time employee ofBoehringer Ingelheim.IRB approval status: Approved (PAR1-14-442,PAR1-14-443).Reprints not available from the authors.Correspondence to: Marjolein de Bruin-Weller, MD,PhD, University Medical Center Utrecht,Heidelberglaan 100, 3584 CX Utrecht, theNetherlandsE-mail: m.s.debruin-weller@umcutrecht.nlREFERENCES1. Eckert L, Gupta S, Amand C, Gadkari A, Mahajan P, Gelfand JM.Impact of atopic dermatitis on health-related quality of lifeand productivity in adults in the United States: an analysisusing the National Health and Wellness Survey. J Am AcadDermatol. 2017;77:274-279.2. Ari€ens LFM, van Nimwegen KJM, Shams M, et al. Economicburden of adult patients with moderate to severe atopicdermatitis indicated for systemic treatment. Acta Derm Vene-reol. 2019;99:762-768.3. Simpson EL, Bieber T, Guttman-Yassky E, et al. Two phase 3trials of dupilumab versus placebo in atopic dermatitis. N EnglJ Med. 2016;375:2335-2348.4. Eurostat Statistics Explained. Estimated hourly labour costs inthe European Union. 2017. Available at: https://ec.europa.eu/eurostat/statistics-explained/index.php/Hourly_labour_costs.Accessed October 22, 2019.5. US Bureau of Labor Statistics. Employer costs for employeecompensation (June 2018). Available at: https://www.bls.gov/news.release/pdf/ecec.pdf. Accessed October 24, 2019.https://doi.org/10.1016/j.jaad.2020.05.142J AM ACAD DERMATOLVOLUME jj, NUMBER jLetter 3

Eckert

Ariëns

Simpson

Crossref

https://eprints.whiterose.ac.uk/166195/1/1-s2.0-S0190962220310197-main.pdf

Dupilumab reduces absenteeism in patients with moderate to severe atopic dermatitis: Pooled results from the LIBERTY AD SOLO clinical trials

Abstract

Similar works

Full text

Available Versions

White Rose Research Online

White Rose Research Online

Crossref