[Cost-Utility Analysis of Dupilumab for the Treatment of Severe Atopic Dermatitis in Children and Adolescents in Italy]

Elena Galli, Maria Paola Pedone, Miryana Dobreva, Rossella Bitonti, Roberta Di Turi

DOI: https://doi.org/10.7175/fe.v23i1.1527


BACKGROUND AND OBJECTIVE: Atopic dermatitis (AD) is a chronic, multifactorial, inflammatory condition characterized by a significant impact on patients’ quality of life. Dupilumab is reimbursed by the Italian Medicines Agency (AIFA) for the treatment of adolescent and adult patients with severe AD (according to AIFA registry criteria). Recently, dupilumab has been reimbursed in the treatment of children with severe AD. The objective of this analysis was to estimate the incremental cost-utility ratio (ICUR) of dupilumab compared to current supportive care (SC), for the treatment of severe AD in children (6-11 years) and adolescents (12-17 years) in Italy.

MATERIALS AND METHODS: Cost-effectiveness analysis was conducted using a 1-year decision tree followed by a Markov model over a lifetime period. The base case analysis was performed on the overall population of the LIBERTY AD ADOL (NCT03054428) and LIBERTY AD PEDS (NCT03345914) studies, adopting the National Health Service (NHS) perspective. The following costs were considered: acquisition of treatment, management of disease, adverse events and complications. The robustness of the model was tested through sensitivity analysis. In addition, a scenario analysis adopting the social perspective was performed.

RESULTS: In the base case, over a lifetime, dupilumab was more effective than SC in both children and adolescents (+2.44 and +1.62 quality-adjusted life years—QALYs, respectively). The introduction of dupilumab generated an increase in treatment costs (+€ 64,800 and +€ 52,853 € for children and adolescents, respectively), partially offset by a decrease in the costs of disease management and complications. Incremental cost-utility ratios (ICURs) were € 21,189 per QALY gained, for children, and € 26,569 per QALY gained, for adolescents. In both cases, the ICUR was lower than the willingness to pay threshold considered in Italy (€ 50,000 per QALY gained). Both the deterministic and probabilistic sensitivity analysis confirmed the robustness of the base case results. Finally, the scenario analysis, adopting the social perspective, showed coherent results compared to the base case.

DISCUSSION: Dupilumab is a cost-effective option for the treatment of children and adolescents with severe AD eligible for systemic treatment in Italy compared to SC, from both the NHS and social perspective, confirming the results obtained in the adult population.


Atopic dermatitis; Cost-utility analysis; Dupilumab; Pediatrics

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  • Bylund S, Von Kobyletzki LB, Svalstedt M, et al. Prevalence and incidence of atopic dermatitis: A systematic review. Acta Derm Venereol 2020;100:320-9; https://doi.org/10.2340/00015555-3510
  • Kim BS. Atopic Dermatitis. Medscape, 2021. Available at: https://emedicine.medscape.com/article/1049085-overview (last accessed June 2022)
  • Gandhi NA, Bennett BL, Graham NMH, et al. Targeting key proximal drivers of type 2 inflammation in disease. Nat Rev Drug Discov 2016;15:35-50; https://doi.org/10.1038/nrd4624
  • Mortz CG, Andersen KE, Dellgren C, et al. Atopic dermatitis from adolescence to adulthood in the TOACS cohort: prevalence, persistence and comorbidities. Allergy 2015;70:836-45; https://doi.org/10.1111/all.12619
  • Drucker AM. Atopic dermatitis: Burden of illness, quality of life, and associated complications. Allergy Asthma Proc 2017;38:3-8; https://doi.org/10.2500/aap.2017.38.4005
  • Gelmetti C, Girolomoni G, Patrizi A. Revisione critica di linee guida e raccomandazioni pratiche per la gestione dei pazienti con dermatite atopica, 2016. Available at: https://www.pacinimedicina.it/wp-content/uploads/dermatite-atopica_sidemast.pdf (last accessed June 2022)
  • Flohr C, Mann J. New insights into the epidemiology of childhood atopic dermatitis. Allergy 2014;69:3-16; https://doi.org/10.1111/all.12270
  • El Hachem M, Naldi L, Neri I, et al. Atopic dermatitis in schoolchildren and adolescents: a critical review of Italian epidemiological data and systemic treatments. Ital J Dermatol Venerol 2021;156:650-8; https://doi.org/10.23736/S0392-0488.20.06669-9
  • von Kobyletzki LB, Bornehag C-G, Breeze E, et al. Factors associated with remission of eczema in children: a population-based follow-up study. Acta Derm Venereol 2014;94:179-84; https://doi.org/10.2340/00015555-1681
  • Galli E, Cinicola B, Carello R, et al. Atopic dermatitis. Acta Biomed 2020;91:e2020011; https://doi.org/10.23750/abm.v91i11-S.10313
  • Ricci G, Bendandi B, Bellini F, et al. Atopic dermatitis: quality of life of young Italian children and their families and correlation with severity score. Pediatr Allergy Immunol 2007;18:245-9; https://doi.org/10.1111/j.1399-3038.2006.00502.x
  • Galli E, Ricci G, Maiello N, et al.Position Paper sulla gestione della dermatite atopica moderata-grave in età pediatrica della Società Italiana di Allergologia e Immunologia Pediatrica (SIAIP), della Società Italiana di Dermatologia Pediatrica (SIDerP) e della Società Italiana di Pediatria (SIP). Rivista di Immunologia e Allergologia Pediatrica 2021;35(suppl1):1-34
  • Chiricozzi A, Belloni Fortina A, Galli E, et al. Current therapeutic paradigm in pediatric atopic dermatitis: Practical guidance from a national expert panel. Allergol Immunopathol 2019;47:194-206; https://doi.org/10.1016/j.aller.2018.06.008
  • Megna M, Napolitano M, Patruno C, et al. Systemic Treatment of Adult Atopic Dermatitis: A Review. Dermatol Ther 2017;7:1-23; https://doi.org/10.1007/s13555-016-0170-1
  • Ciclosporina. Riassunto delle caratteristiche del prodotto. Available at: https://farmaci.agenziafarmaco.gov.it/aifa/servlet/PdfDownloadServlet?pdfFileName=footer_001392_046088_RCP.pdf&retry=0&sys=m0b1l3 (last accessed June 2022)
  • Bieber T, Straeter B. Off-label prescriptions for atopic dermatitis in Europe. Allergy 2015;70:6-11; https://doi.org/10.1111/all.12498
  • Galli E, Ricci G. Dermatite atopica moderata-grave dell’adolescente e terapia con il farmaco biologico dupilumab. Rivista di Immunologia e Allergologia Pediatrica 2020;34:22-9
  • Dupixent. Riassunto delle caratteristiche del prodotto. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/004390/WC500236507.pdf (last accessed June 2022)
  • Simpson EL, Paller AS, Siegfried EC, et al. Efficacy and Safety of Dupilumab in Adolescents with Uncontrolled Moderate to Severe Atopic Dermatitis: A Phase 3 Randomized Clinical Trial. JAMA Dermatology 2020;156:44-56; https://doi.org/10.1001/jamadermatol.2019.3336
  • Paller AS, Siegfried EC, Thaçi D, et al. Efficacy and safety of dupilumab with concomitant topical corticosteroids in children 6 to 11 years old with severe atopic dermatitis: A randomized, double-blinded, placebo-controlled phase 3 trial. J Am Acad Dermatol 2020;83:1282-93; https://doi.org/10.1016/j.jaad.2020.06.054
  • Agenzia Italiana del Farmaco (AIFA). Regime di rimborsabilità e prezzo del medicinale per uso umano «Dupixent». GU Serie Generale n.208 del 07-09-2018
  • Agenzia italiana del farmaco (AIFA). Determina 8 ottobre 2020. GU Serie Generale n.256 del 16-10-2020. Available at: https://www.gazzettaufficiale.it/eli/gu/2020/10/16/256/sg/pdf (last accessed June 2022)
  • Agenzia italiana del farmaco (AIFA). Determina 24 novembre 2020 GU Serie Generale n.305 del 09-12-2020. Available at: https://www.gazzettaufficiale.it/eli/gu/2020/12/09/305/sg/pdf (last accessed June 2022)
  • Agenzia Italiana del Farmaco (AIFA). Determina n. 115. Regime di rimborsabilità e prezzo, a seguito di nuove indicazioni terapeutiche, del medicinale per uso umano «Dupixent». GU Serie Generale n.42 del 19-02-2022
  • Agenzia Italiana del Farmaco (AIFA). Determina n. 116. Regime di rimborsabilità e prezzo, a seguito di nuove indicazioni terapeutiche, del medicinale per uso umano «Dupixent». GU Serie Generale n.42 del 19-02-2022
  • Woolacott N, Hawkins N, Mason A, et al. Etanercept and efalizumab for the treatment of psoriasis: A systematic review. Health Technology Assessment 2006;10:1-233; https://doi.org/10.3310/hta10460
  • Pan F, Brazier NC, Shear NH, et al. Cost utility analysis based on a head-to-head phase 3 trial comparing ustekinumab and etanercept in patients with moderate-to-severe plaque psoriasis: A Canadian perspective. Value Heal 2011;14:652-6; https://doi.org/10.1016/j.jval.2011.01.006
  • Sizto S, Bansback N, Feldman SR, et al. Economic evaluation of systemic therapies for moderate to severe psoriasis. Br J Dermatol 2009;160:1264-72; https://doi.org/10.1111/j.1365-2133.2008.08962.x
  • Anis AH, Bansback N, Sizto S, et al. Economic evaluation of biologic therapies for the treatment of moderate to severe psoriasis in the United States. J Dermatolog Treat 2011;22:65-74; https://doi.org/10.3109/09546630903551258
  • Colombo GL, Di Matteo S, Peris K, et al. A cost-utility analysis of etanercept for the treatment of moderate-to-severe psoriasis in Italy. Clinicoecon Outcomes Res 2009;1:53-9 https://doi.org/10.2147/CEOR.S7348
  • Graham C, Mollon P, Miles L, et al. A New Cost-Effectiveness Framework For Modeling Psoriasis Treatments. Value Heal 2015; https://doi.org/10.1016/j.jval.2015.03.126
  • Institute for Clinical and Economic Review. Targeted immunomodulators for the treatment of moderate-to-severe plaque psoriasis: effectiveness and value. 2016. Available at: https://icer.org/wp-content/uploads/2020/10/NE_CEPAC_Psoriasis_Evidence_Report_FINAL_012317.pdf (last accessed June 2022)
  • Rodgers M, Epstein D, Bojke L, et al. Etanercept, infliximab and adalimumab for the treatment of psoriatic arthritis: A systematic review and economic evaluation. Health Technol Assess 2011;15:1-329; https://doi.org/10.3310/hta15100
  • Bojke L, Epstein D, Craig D, et al. Modelling the cost-effectiveness of biologic treatments for psoriatic arthritis. Rheumatology 2011;50:iv39-iv47; https://doi.org/10.1093/rheumatology/ker245
  • Cawson MR, Mitchell SA, Knight C, et al. Systematic review, network meta-analysis and economic evaluation of biological therapy for the management of active psoriatic arthritis. BMC Musculoskeletal Disord 2014;15:26; https://doi.org/10.1186/1471-2474-15-26
  • National Institute for Health and Care Excellence (NICE). Dupilumab for treating moderate to severe atopic dermatitis, 2018. Available at: https://www.nice.org.uk/guidance/ta534 (last accessed June 2022)
  • Costanzo A, Furneri G, Bitonti R, et al. Cost-effectiveness analysis of dupilumab for the treatment of severe atopic dermatitis in adults in Italy. Glob Reg Heal Technol Assess 2020;7:57-65; https://doi.org/10.33393/grhta.2020.710
  • Blauvelt A, de Bruin-Weller M, Gooderham M, et al. 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. Lancet 2017;389:2287-303; https://doi.org/10.1016/S0140-6736(17)31191-1
  • Linee Guida AIFA per le analisi farmacoeconomiche, 2021. Available at: https://www.aifa.gov.it/documents/20142/1307543/2021.01.22_estratto_linee_guida_sezione_E.pdf (last accessed June 2022)
  • Cork MJ, Thaçi D, Eichenfield LF, et al. Dupilumab provides favourable long-term safety and efficacy in children aged ≥ 6 to < 12 years with uncontrolled severe atopic dermatitis: results from an open-label phase IIa study and subsequent phase III open-label extension study. Br J Dermatol 2021;184:857-70; https://doi.org/10.1111/bjd.19460
  • Sanofi. SAR231893. AD1224. CHRONOS - FAS population. Data on file, 2016
  • Sanofi. Summary of the persistence of utility effect survey. Data on file, 2017
  • Simpson EL, Bieber T, Guttman-Yassky E, et al. Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis. N Engl J Med 2016;375:2335-48; https://doi.org/10.1056/NEJMoa1610020
  • Sanofi. SAR231893. OVERALL. SOLO 1 & SOLO 2 - FAS population. Data on file, 2016
  • Regeneron Pharmaceuticals (Regeneron). Dupilumab - R668-AD-1225. Data on file, 2017
  • Ricci G, Bendandi B, Pagliara L, et al. Atopic Dermatitis in Italian Children: Evaluation of Its Economic Impact. J Pediatr Heal Care 2006;20:311-5; https://doi.org/10.1016/j.pedhc.2006.04.009
  • Ministero della Salute. Progetto Mattoni SSN. Pronto Soccorso e sistema 118. Proposta metodologica per la valutazione dei costi dell’emergenza, 2007. Available at: http://www.mattoni.salute.gov.it/mattoni/documenti/11_Valutazione_costi_dell_emergenza.pdf (last accessed June 2022)
  • Istituto Nazionale di Statistica (ISTAT). Calcolo delle rivalutazioni monetarie. Available at: https://rivaluta.istat.it/ (last accessed June 2022)
  • Ministero della salute. Tariffe delle prestazioni ospedaliere. Supplemento n. 8, Gazzetta Ufficiale n. 23, 2013. Allegato 1 e 3
  • Ara R, Brazier JE. Using health state utility values from the general population to approximate baselines in decision analytic models when condition-specific data are not available. Value Heal 2011;14:539-45; https://doi.org/10.1016/j.jval.2010.10.029
  • Sanofi. EpiCARE UK study. Data on file, 2019
  • Sanofi. AWARE study. Data on file, 2017
  • Martone N, Lucioni C, Mazzi S, et al. Valutazione di costo-efficacia dei nuovi farmaci oncologici immessi sul mercato italiano. Glob Reg Heal Technol Assess 2014;1:31-43
  • Marseille E, Larson B, Kazi DS, et al. Thresholds for the cost–effectiveness of interventions: alternative approaches. Bull World Health Organ 2015;93:118-24; https://doi.org/10.2471/BLT.14.138206
  • Jommi C, Cipriani F, Fanelli, et al. L’impatto della cross-copertura di dupilumab sulla spesa a carico del Servizio Sanitario Nazionale. GRHTA 2020;7:33-9; https://doi.org/10.33393/grhta.2020.2139
  • Fattore, G. Proposta di linee guida per la valutazione economica degli interventi sanitari in Italia. Pharmacoeconomics-Ital-Res-Articles 2009;11:83-93; https://doi.org/10.1007/BF03320660
  • Mohr N, Naatz M, Zeervi L, et al. Cost-of-illness of atopic dermatitis in Germany: data from dermatology routine care. J Eur Acad Dermatology Venereol 2021;35:1346-56; https://doi.org/10.1111/jdv.17203
  • Toron F, Neary MP, Smith TW, et al. Clinical and Economic Burden of Mild-to-Moderate Atopic Dermatitis in the UK: A Propensity-Score-Matched Case–Control Study. Dermatol Ther 2021;11:907-28; https://doi.org/10.1007/s13555-021-00519-7


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