Cost-effectiveness analysis of caplacizumab in the new standard of care for immune Thrombotic Thrombocytopenic Purpura in Italy


  • Giovanni Di Minno Regional Reference Center for Coagulation Disorders, Federico II University Hospital, Naples - Italy
  • Roberto Ravasio HEOR and RWE Lead, Market Access Provider, Milan - Italy



Caplacizumab, Cost-effectiveness, Hospital, Immune Thrombotic Thrombocytopenic Purpura, Orphan drug, Rare blood disorders


Objectives: To evaluate the cost-effectiveness analysis (CEA) of caplacizumab in combination with plasmapheresis (PEX) and immunosuppression compared to PEX and immunosuppression in the treatment of acute episodes of iTTP.

Methods: A Markov model was used to conduct the CEA from the perspective of the hospital, over a lifetime horizon. Clinical data derived from HERCULES trial and a systematic literature review. Economic input included direct costs only. Utility and disutility values were obtained from literature. Data on healthcare resources and costs were retrieved from HERCULES trial, literature, TTP guidelines and Italian tariffs. A sensitivity analysis was conducted. The cost-effectiveness probability was tested for several options of discount levels considering a suggested willingness to pay (WTP) threshold of € 60,000 in Italy.

Results: The use of caplacizumab in combination with PEX and immunosuppression is associated with a positive difference in survival of 3.27 life years (24.53 vs 21.26) and in quality of life of 3.06 QALY (22.01 vs 18.96) when compared to PEX and immunosuppression. Caplacizumab leads to an ICER per life years of € 41,653 and an ICER per QALY of € 44,572. For the suggested WTP threshold, the probability of caplacizumab being cost-effective is 82.4% (no discount), 92.8% (15% discount), 95.3% (20% discount), 96.9% (25% discount) and 98.2% (30% discount).

Conclusions: Caplacizumab in addition to PEX and immunosuppression is cost-effective, allowing the hospital to achieve greater efficiency in managing the burden of a life-threatening disease such as iTTP.


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Osservatorio Malattie Rare (OMAR). (accessed december, 2019).

Taruscio D. 17/8 - Il Registro Nazionale Malattie Rare nel contesto nazionale e internazionale. 3° Rapporto (dati al 31 dicembre 2014). 2017. (accessed december, 2019).

Scully M, Yarranton H, Liesner R, et al. Regional UK TTP registry: correlation with laboratory ADAMTS 13 analysis and clinical features. Br J Haematol. 2008;142(5):819-826. PMID:18637802

Joly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood. 2017;129(21):2836-2846. PMID:28416507

Sadler JE. What’s new in the diagnosis and pathophysiology of thrombotic thrombocytopenic purpura. Hematology (Am Soc Hematol Educ Program). 2015;2015(1):631-636. PMID:26637781

Callewaert F, Roodt J, Ulrichts H, et al. Evaluation of efficacy and safety of the anti-VWF Nanobody ALX-0681 in a preclinical baboon model of acquired thrombotic thrombocytopenic purpura. Blood. 2012;120(17):3603-3610.

Terrell DR, Williams LA, Vesely SK, Lämmle B, Hovinga JA, George JN. The incidence of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: all patients, idiopathic patients, and patients with severe ADAMTS-13 deficiency. J Thromb Haemost. 2005;3(7):1432-1436. PMID:15978100

Kremer Hovinga JA, Coppo P, Lämmle B, Moake JL, Miyata T, Vanhoorelbeke K. Thrombotic thrombocytopenic purpura. Nat Rev Dis Primers. 2017;3(1):17020. PMID:28382967

Bennett CL, Djulbegovic B. Thrombotic thrombocytopenic purpura: gaining knowledge. Lancet Haematol. 2016;3(5):e210-e211.

Falter T, Alber KJ, Scharrer I. Long term outcome and sequelae in patients after acute thrombotic thrombocytopenic purpura episodes. Hamostaseologie. 2013;33(2):113-120. PMID:23599034

Reese JA, Muthurajah DS, Kremer Hovinga JA, Vesely SK, Terrell DR, George JN. Children and adults with thrombotic thrombocytopenic purpura associated with severe, acquired Adamts13 deficiency: comparison of incidence, demographic and clinical features. Pediatr Blood Cancer. 2013;60(10):1676-1682. PMID:23729372

Miller DP, Kaye JA, Shea K, et al. Incidence of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome. Epidemiology. 2004;15(2):208-215. PMID:15127914

Knoebl P, Cataland S, Peyvandi F, et al. Efficacy and safety of open-label caplacizumab in patients with exacerbations of acquired thrombotic thrombocytopenic purpura in the HERCULES study. J Thromb Haemost. 2020;18(2):479-484. PMID:31691462

Riva S, et al. Long-term neuropsychological sequelae, emotional wellbeing and quality of life in patients with acquired thrombotic thrombocytopenic purpura. Haematologica. 2020;105(7):1957-1962. PMID:31558667

Kennedy AS, Lewis QF, Scott JG, et al. Cognitive deficits after recovery from thrombotic thrombocytopenic purpura. Transfusion. 2009;49(6):1092-1101. PMID:19222817

Scully M, Hunt BJ, Benjamin S, et al; British Committee for Standards in Haematology. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol. 2012;158(3):323-335. PMID:22624596

Scully M, Cataland SR, Peyvandi F, et al; HERCULES Investigators. Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura. N Engl J Med. 2019;380(4):335-346. PMID:30625070

Peyvandi F, Scully M, Kremer Hovinga JA, et al; TITAN Investigators. Caplacizumab for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2016;374(6):511-522. PMID:26863353

Peyvandi F. Integrated Efficacy Results from the Phase II and Phase III Studies with Caplacizumab in Patients with Acquired Thrombotic Thrombocytopenic Purpura. Blood. 2018. 132(Suppl. 1).

Area Strategia ed Economia del Farmaco. Settore HTA ed Economia del Farmaco. Elenco dei farmaci innovativi ai sensi dell’articolo 10, comma 2, legge 8 novembre 2012, n. 189, come definito dall'art. 1 comma 1 e 2 dell'accordo Stato-Regioni del 18 novembre 2010 (Rep. Atti n. 197/CSR). Disponibile su: (accessed august, 2020).

Sonnenberg FA, Beck JR. Markov models in medical decision making: a practical guide. Med Decis Making. 1993;13(4):322-338.

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

Lotta LA, Mariani M, Consonni D, et al. Different clinical severity of first episodes and recurrences of thrombotic thrombocytopenic purpura. Br J Haematol. 2010;151(5):488-494. PMID:20955397

Caro JJ, Briggs AH, Siebert U, Kuntz KM; ISPOR-SMDM Modeling Good Research Practices Task Force. Modeling good research practices—overview: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force—1. Value Health. 2012;15(6):796-803. PMID:22999128

Ablynx Data on file. Systematic review on the clinical burden of disease in thrombotic thrombocytopenic purpura. 2017.

Team RC. A language and environment for statistical computing. R Foundation for Statistical Computing; 2018.

ISTAT. Istituto nazionale di statistica. Tavole di mortalità della popolazione residente: Italia, anno 2017.

Yusuf S, Pitt B, Davis CE, Hood WB Jr, Cohn JN; SOLVD Investigators. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med. 1992;327(10):685-691. PMID:1463530

Rutten-Jacobs LCA, Arntz RM, Maaijwee NA, et al. Long-term mortality after stroke among adults aged 18 to 50 years. JAMA. 2013;309(11):1136-1144. PMID:23512060

Scalone L, Cortesi PA, Ciampichini R, Cesana G, Mantovani LG. Health Related Quality of Life norm data of the general population in Italy: results using the EQ-5D-3L and EQ-5D-5L instruments.

Anie KA, Grocott H, White L, Dzingina M, Rogers G, Cho G. Patient self-assessment of hospital pain, mood and health related quality of life in adults with sickle cell disease. BMJ Open. 2012;2(4):e001274.

NICE Clinical Guideline Centre. Lipid modification: Cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease. Clinical Guideline CD181 Appendices. July 2014.

NICE. NICE TA327. Dabigatran etexilate for the treatment and secondary prevention of deep vein thrombosis and/or pulmonary embolism.

NICE. NICE TA420. Ticagrelor for preventing atherothrombotic events after myocardial infarction.

Sanofi Data on file. Clinical Study Report HERCULES Study.

Pradelli L, Klek S, Mayer K, et al. Omega-3 fatty acid-containing parenteral nutrition in ICU patients: systematic review with meta-analysis and cost-effectiveness analysis. Crit Care. 2020;24(1):634. PMID:33143750

Rapporto sull’attività di ricovero ospedaliero SDO 2018. (accessed january, 2018).

Prestazioni di assistenza specialistica ambulatoriale.

Tariffario Regione Veneto 2017.

Farmadati 2019. Acido Folico (DOC Generici), 5 mg, 120 CPR. Prezzo ex factory al lordo delle riduzioni di legge € 11,25.

Lista farmaci classe A 15-11-19 (ITALIA)SOLUMEDROL, 1 flacone IM EV 1 g + 1 flacone solv 16 ml.

Martone N, Lucioni C, Mazzi S. V. Fadda - Valutazione di costo-efficacia dei nuovi farmaci oncologici immessi sul mercato italiano - Global & Regional Health Technol Assess 2014; 1(2):31-43.

Messori A, Santarlasci B, Trippoli S, Vaiani M. Controvalore economico del farmaco e beneficio clinico: stato dell’arte della metodologia e applicazione di un algoritmo farmacoeconomico. PharmacoEconomics – Ital-Res-Articles. 2003;5(2):53-67.

Messori A, Maratea D, Nozzoli C, Bosi A. The role of bortezomib, thalidomide and lenalidomide in the management of multiple myeloma: an overview of clinical and economic information. Pharmacoeconomics. 2011;29(4):269-285. PMID:21395348



How to Cite

Di Minno, G., & Ravasio, R. (2021). Cost-effectiveness analysis of caplacizumab in the new standard of care for immune Thrombotic Thrombocytopenic Purpura in Italy. Global and Regional Health Technology Assessment, 8(1), 43–52.



Original Research Articles


Received 2020-10-17
Accepted 2021-03-06
Published 2021-04-01


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