Analisi costo-utilità di dupilumab per il trattamento della dermatite atopica grave negli adulti in Italia

Cost-effectiveness analysis of dupilumab for the treatment of severe atopic dermatitis in adults in Italy

  • Antonio Costanzo Dermatology Unit, Department of Biomedical Sciences, Humanitas University, Milan - Italy, and Skin Pathology Laboratory, Humanitas Research Hospital, Rozzano, Milan - Italy
  • Gianluca Furneri EBMA Consulting, Melegnano, Milan - Italy
  • Rossella Bitonti EBMA Consulting, Melegnano, Milan - Italy
  • Maria Paola Pedone Sanofi S.p.A., Milan - Italy
  • Francesca Fanelli Sanofi S.p.A., Milan - Italy
  • Roberta Di Turi UOC Assistenza Farmaceutica, Dipartimento dei Servizi, ASL Roma 3, Rome - Italy
Keywords: Atopic dermatitis, Cost-effectiveness analysis, Dupilumab, QALY

Abstract

Background
Atopic dermatitis (AD) is a chronic, multifactorial, inflammatory skin disease with significant impact on patients’ quality of life.

Objective
The objective of this analysis was to estimate the incremental cost-effectiveness ratio (ICER) of dupilumab, administered every other week, vs supportive care (SC), in the Italian adult population with severe AD, for whom ciclosporin treatment is contraindicated, ineffective or not tolerated.

Methods
Simulation of outcomes and costs was undertaken using a 1-year decision tree, followed by a 20-year time horizon Markov model. Clinical data were derived from a pooled analysis of two studies. Given the uncertainty on final National Health Service (NHS) cost of dupilumab in Italy (confidential discount might be applied) multiple cost-utility analyses were conducted using different price hypotheses, starting from dupilumab published ex-manufacturer price, and progressively reducing it up to 50%. Model robustness were tested using sensitivity analyses.

Results
In the base-case, dupilumab was more effective than SC (+1.92 quality adjusted life years, QALYs). In Analysis A (NHS perspective), -8.0% discount on dupilumab ex-manufacturer price was required to achieve an ICER<€50,000 QALY gained with dupilumab vs SC; in Analysis B (Societal perspective), dupilumab ICER vs SC was already below the acceptability threshold at its current published ex-manufacturer price. Both one-way deterministic and probabilistic sensitivity analyses confirmed robustness and reliability of base-case results.

Conclusions
Dupilumab is a cost-effective option for the treatment of patients with severe AD in Italy, compared with SC, when both NHS and societal economic consequences of AD treatment and management are considered.

References

Società Italiana di Allergologia e Immunologia Pediatrica. La gestione clinica della dermatite atopica in età pediatrica. http://www.riaponline.it/wp-content/uploads/2015/05/RivRiap_suppl2_2_151.pdf (Data ultimo accesso 01/12/2018).

Medscape. Atopic Dermatitis. Practise essentials. https://emedicine.medscape.com/article/1049085-overview (Data ultimo accesso 01/12/2018).

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.

Kim J, Kim BE, Leung DYM. Pathophysiology of atopic dermatitis: Clinical implications. Allergy Asthma Proc. 2019;40:84-92.

Flohr C, Mann J. New insights into the epidemiology of childhood atopic dermatitis. Allergy: European Journal of Allergy and Clinical Immunology. 2014;69(1):3-16.

Società Italiana di Dermatologia Medica, Chirurgia, Estetica e delle Malattie sessualmente trasmesse. Dermatite atopica. http://www.pacinimedicina.it/dermatite-atopica-linee-guida-sidemast-2016-2017/ (Data ultimo accesso 01/12/2018).

Barbarot S, Auziere S, Gadkari A, et al. Epidemiology of atopic dermatitis in adults: Results from an international survey. Allergy. 2018;73(6):1284-93.

Drucker AM. Atopic dermatitis: Burden of illness, quality of life, and associated complications. Allergy Asthma Proc. 2017;38(1):3-8.

Hajar T, Gontijo JRV, Hanifin JM. New and developing therapies for atopic dermatitis. An Bras Dermatol. 2018;93:104-7.

Megna M, Napolitano M, Patruno C, et al. Systemic Treatment of Adult Atopic Dermatitis: A Review. Dermatol Ther (Heidelb). 2017;7:1-23.

Bieber T, Straeter B. Off-label prescriptions for atopic dermatitis in Europe. Allergy. 2015;70:6-11.

Agenzia Europea per i Medicinali (EMA). Dupixent (Dupilumab). Riassunto caratteristiche prodotto. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/004390/WC500236507.pdf (Data ultimo accesso 01/12/2018).

Crepy M, Nosbaum A, Bensefa‐Colas L. Blocking type 2 inflammation by dupilumab does not control classic (type 1‐driven) allergic contact dermatitis in chronic hand eczema. Contact Dermatitis. 2019;81(2):145-7.

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(24):2335-48.

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.

de Bruin-Weller M, Thaçi D, Smith CH, et al. Dupilumab with concomitant topical corticosteroid treatment in adults with atopic dermatitis with an inadequate response or intolerance to ciclosporin A or when this treatment is medically inadvisable: a placebo-controlled, randomized phase III clinical t. Br J Dermatol. 2018;178:1083-101.

Agenzia Italiana del farmaco (AIFA). Farmaci innovativi oncologici sottoposti a registro di monitoraggio. http://www.aifa.gov.it/sites/default/files/farmaci_innovativi_monitoraggio_01.10.2018.pdf (Data ultimo accesso 01/12/2018).

Woolacott N, Hawkins N, Mason A, et al. Etanercept and efalizumab for the treatment of psoriasis: A systematic review. Health Technol Assess. 2006;10(46):1-233,i-iv.

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(5):652-6.

Sizto S, Bansback N, Feldman SR, et al. Economic evaluation of systemic therapies for moderate to severe psoriasis. Br J Dermatol. 2009;160(6):1264-72.

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(2):65-74.

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.

Graham C, Mollon P, Miles L, et al. A New Cost-Effectiveness Framework For Modeling Psoriasis Treatments. Value Heal. 2015;18(3):A20.

Institute for Clinical and Economic Review. Targeted immunomodulators for the treatment of moderate-to-severe plaque psoriasis: effectiveness and value. Dicembre 2016. Disponibile: https://icer-review.org/wp-content/uploads/2016/12/NE_CEPAC_Psoriasis_Evi (Data ultimo accesso 01/12/2018).

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(10):i-xxi,1-329.

Bojke L, Epstein D, Craig D, et al. Modelling the cost-effectiveness of biologic treatments for psoriatic arthritis. Rheumatology. 2011;50 Suppl.4:iv39-iv47.

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 Musculoskelet Disord. 2014;15:26.

Graham CN, Gunda P, Miles L, et al. A new cost-effectiveness framework for modeling psoriatic arthritis treatments. Value Heal. 2016;19(3):A233-4.

Woolacott N, Vergel YB, Hawkins N, et al. Etanercept and infliximab for the treatment of psoriatic arthritis: A systematic review and economic evaluation. Health Technol Assess. 2006;10(31):iii-iv,xiii-xvi,1-239.

National Institute for Health and Care Excellence (NICE). Dupilumab for treating moderate to severe atopic dermatitis. https://www.nice.org.uk/guidance/ta534 (Data ultimo accesso 01/12/2018).

Fattore G. Proposta di Linee Guida per la valutazione economica degli interventi sanitari in Italia. PharmacoEconomics – Italian Research Articles. 2009;11(2):83-93.

Sanofi. SAR231893. AD1224. CHRONOS – CAFÉ like population. Data on file. October 24, 2016a.

Istituto nazionale di statistica (ISTAT). Tavole di mortalità della popolazione residente: Italia. http://demo.istat.it/tvm2016/index.php?lingua=ita (Data ultimo accesso 01/12/2018).

McKenna C, McDaid C, Suekarran S, et al. Enhanced external counterpulsation for the treatment of stable angina and heart failure: A systematic review and economic analysis. Health Technol Assess. 2009;13(24):iii-iv,ix-xi,1-90.

Sanofi. Persistence of the quality of life gain in AD. Data on file. October 19, 2017f.

Sanofi. UK model with adaptations. Data on file. November 14, 2017g.

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. Disponibile sul sito: https://www.gazzettaufficiale.it/eli/gu/2018/09/07/208/sg/pdf.

Silverberg JI, Simpson EL. Association between severe eczema in children and multiple comorbid conditions and increased healthcare utilization. Pediatr Allergy Immunol. 2013;24(5):476-86.

Clinical expert opinion to determine monitoring costs associated to AD treatments. 2018. Data on file.

Sicras-Mainar A, Navarro-Artieda R, Carrascosa Carrillo JM. Economic Impact of Atopic Dermatitis in Adults: A Population-Based Study (IDEA Study). Actas Dermosifiliogr. 2018;109:35-46.

Ministero della Salute. Progetto Mattoni SSN. Pronto Soccorso e sistema 118. Proposta metodologica per la valutazione dei costi dell’emergenza. Disponibile sul sito: http://www.mattoni.salute.gov.it/mattoni/documenti/11_Valutazione_costi_dell_emergenza.pdf (Data ultimo accesso 01/12/2018).

Ministero della salute. Tariffe delle prestazioni ambulatoriali. Supplemento n. 8, Gazzetta Ufficiale n. 23, 2013. Allegato http://www.trovanorme.salute.gov.it/norme/renderPdf.spring?seriegu=SG&datagu=28/01/2013&redaz=13A00528&artp=3&art=1&subart=1&subart1=10&vers=1&prog=001.

Codifa. L’informatore farmaceutico. OFTACILOX. 0,3% unguento oftalmico tubo 3,5 g. Disponibile: https://www.codifa.it/cont/codica-ricerca/27/ricerca.asp?id_scheda=3810 (Data ultimo accesso 01/12/2018).

SISAC. Verbale preintesa – Ipotesi di Accordo Collettivo Nazionale per la Disciplina dei rapporti con i medici di medicina generale 2019. Disponibile: https://www.quotidianosanita.it/allegati/allegato2327959.pdf (Data ultimo accesso 30/06/2020).

Poole CD, Bannister CA, Andreasen JN, et al. Estimation of health-related utility (EQ-5D index) in subjects with seasonal allergic rhinoconjunctivitis to evaluate health gain associated with sublingual grass allergen immunotherapy. Health Qual Life Outcomes. 2014;12:99.

Federal Joint Commitee (G-BA). Benefit Assessment of Dupilumad. https://www.g-ba.de/downloads/39-261-3314/2018-05-17_AM-RL-XII_Dupilumab_D-328_BAnz.pdf (Data ultimo accesso 01/12/2018).

Haute Autorité de Santé. Opinion of the Transparency Committee on Dupilumab. https://www.has-sante.fr/portail/jcms/c_2865400/fr/dupixent-dupilumab-medicament-de-la-dermatite-non-corticoide (Data ultimo accesso 01/12/2018).

Published
2020-08-24
How to Cite
CostanzoA., FurneriG., BitontiR., PedoneM. P., FanelliF., & Di TuriR. (2020). Analisi costo-utilità di dupilumab per il trattamento della dermatite atopica grave negli adulti in Italia. Global & Regional Health Technology Assessment, 7(1), 57-65. https://doi.org/10.33393/grhta.2020.710
Section
Original Research Article