A pharmacoeconomic analysis from Italian guidelines for the management of prolactinomas

Authors

  • Michele Basile High School of Economy and Management of Health Systems, Catholic University of Sacred Heart, Rome https://orcid.org/0000-0002-1098-2648
  • Ilaria Valentini High School of Economy and Management of Health Systems, Catholic University of Sacred Heart, Rome https://orcid.org/0000-0001-5940-7495
  • Roberto Attanasio AME Scientific Committee, Milan https://orcid.org/0000-0002-1417-287X
  • Renato Cozzi ASST Grande Ospedale Metropolitano Niguarda, Endocrinology Department, Milan https://orcid.org/0000-0003-0421-5589
  • Agnese Persichetti Ministry of Interior, Department of Firefighters, Public Rescue and Civil Defense, Rome
  • Irene Samperi Endocrinology, ASL Novara, Piedmont
  • Alessandro Scoppola Endocrinology, Ospedale Santo Spirito, Rome https://orcid.org/0000-0002-6490-0978
  • Renata Simona Auriemma Department of Clinical Medicine and Surgery, Endocrinology Section, ‘Federico II’ University of Naples, Naples
  • Ernesto De Menis Internal Medicine 2, Treviso Hospital, Treviso and Functional Department of Endocrinology and Metabolism, AULSS 2 Veneto https://orcid.org/0009-0009-6043-3725
  • Felice Esposito Neurosurgical Clinic, Department of Neurosciences and Reproductive and Odontostomatological Sciences, Federico II’ University of Naples, Naples
  • Emanuele Ferrante Endocrinology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan https://orcid.org/0000-0002-0556-7650
  • Giuseppe Iatì Department of Radiation Oncology, University of Messina, Messina
  • Diego Mazzatenta Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma Neurochirurgia Ipofisi - Pituitary Unit, Bologna https://orcid.org/0000-0002-2466-8828
  • Maurizio Poggi Endocrinology, Department of Clinical and Molecular Medicine, S. Andrea Hospital, Sapienza University of Rome, Rome
  • Roberta Rudà Division of Neurology, Castelfranco Veneto and Treviso Hospital, Treviso Division of Neuro-Oncology, Department of Neuroscience “Rita Levi Montalcini”, University of Turin, Turin
  • Fabio Tortora Radiology Unit, Department of Advanced Biomedical Sciences, University “Federico II”, Naples
  • Fabio Cruciani Department of Epidemiology, Lazio Region Health Service, Rome https://orcid.org/0000-0001-5533-8357
  • Zuzana Mitrova Department of Epidemiology, Lazio Region Health Service, Rome - Italy https://orcid.org/0000-0002-7644-7939
  • Rosella Saulle Department of Epidemiology, Lazio Region Health Service, Rome https://orcid.org/0000-0003-4358-0415
  • Simona Vecchi Department of Epidemiology, Lazio Region Health Service, Rome https://orcid.org/0000-0002-3893-8403
  • Paolo Cappabianca Neurosurgical Clinic, Department of Neurosciences and Reproductive and Odontostomatological Sciences, Federico II’ University of Naples, Naples
  • Agostino Paoletta ULSS6 Euganea, Endocrinology, Padova
  • Alessandro Bozzao Neuroradiology, S. Andrea Hospital, NESMOS Department (Neuroscience, Mental Health, Sensorial Organs), Sapienza University of Rome, Rome https://orcid.org/0000-0002-8865-0723
  • Marco Caputo Laboratorio Analisi Cliniche e Microbiologia, Synlab SRL, Calenzano (FI)
  • Francesco Doglietto Institute of Neurosurgery, Catholic University School of Medicine, Rome https://orcid.org/0000-0002-7438-0734
  • Francesco Ferraù Department of Human Pathology of Adulthood and Childhood ‘G. Barresi’, University of Messina, Messina https://orcid.org/0000-0002-7472-6598
  • Andrea Gerardo Lania Department of Biomedical Sciences, Endocrinology Unit, Humanitas Clinical and Research Center IRCCS, Humanitas University, Rozzano (MI)
  • Stefano Laureti General Practitioner, USL Umbria 1, Perugia
  • Stefano Lello Department of Woman and Child Health and Public Health, Institute of Obstetrics and Gynecology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome https://orcid.org/0000-0002-1616-9105
  • Davide Locatelli Division of Neurosurgery, Department of Biotechnology and Life Sciences, University of Insubria, ASST Sette Laghi, Varese
  • Pietro Maffei Department of Medicine (DIMED), 3rd Medical Clinic, Padua University, Padua https://orcid.org/0000-0002-1717-263X
  • Giuseppe Minniti Department of Medicine, Surgery and Neurosciences, University of Siena, Siena https://orcid.org/0000-0003-1239-1603
  • Alessandro Peri Pituitary Diseases and Sodium Alterations Unit, AOU Careggi, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence
  • Chiara Ruini Department of Psychology, University of Bologna, Bologna https://orcid.org/0000-0002-7805-3183
  • Fabio Settanni Clinical Biochemistry Laboratory, City of Health and Science University Hospital, Turin
  • Antonio Silvani Department of Neuro-Oncology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano
  • Nadia Veronese ASST Grande Ospedale Metropolitano Niguarda, Endocrinology Department, Milan
  • Franco Grimaldi AME past president, Udine https://orcid.org/0000-0002-7527-8010
  • Enrico Papini Endocrinology, Ospedale Regina Apostolorum, Albano Laziale (RM) - Italy
  • Americo Cicchetti High School of Economy and Management of Health Systems, Catholic University of Sacred Heart, Rome

DOI:

https://doi.org/10.33393/grhta.2024.2601

Keywords:

Bromocriptine, Cabergoline, Cost-utility, ICER, Prolactinoma

Abstract

Background: Prolactinoma, the most common pituitary adenoma, is usually treated with dopamine agonist (DA) therapy like cabergoline. Surgery is second-line therapy, and radiotherapy is used if surgical treatment fails or in relapsing macroprolactinoma.

Objective: This study aimed to provide economic evidence for the management of prolactinoma in Italy, using a cost-of-illness and cost-utility analysis that considered various treatment options, including cabergoline, bromocriptine, temozolomide, radiation therapy, and surgical strategies.

Methods: The researchers conducted a systematic literature review for each research question on scientific databases and surveyed a panel of experts for each therapeutic procedure’s specific drivers that contributed to its total cost.

Results: The average cost of the first year of treatment was €2,558.91 and €3,287.40 for subjects with microprolactinoma and macroprolactinoma, respectively. Follow-up costs from the second to the fifth year after initial treatment were €798.13 and €1,084.59 per year in both groups. Cabergoline had an adequate cost-utility profile, with an incremental cost-effectiveness ratio (ICER) of €3,201.15 compared to bromocriptine, based on a willingness-to-pay of €40,000 per quality-adjusted life year (QALY) in the reference economy. Endoscopic surgery was more cost-effective than cabergoline, with an ICER of €44,846.64. Considering a willingness-to-pay of €40,000/QALY, the baseline findings show cabergoline to have high cost utility and endoscopic surgery just a tad above that.

Conclusions: Due to the favorable cost-utility profile and safety of surgical treatment, pituitary surgery should be considered more frequently as the initial therapeutic approach. This management choice could lead to better outcomes and an appropriate allocation of healthcare resources.

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References

Chanson P, Maiter D. The epidemiology, diagnosis and treatment of prolactinomas: the old and the new. Best Pract Res Clin Endocrinol Metab. 2019;33(2):101290. https://doi.org/10.1016/j.beem.2019.101290 PMID:31326373 DOI: https://doi.org/10.1016/j.beem.2019.101290

Vroonen L, Daly AF, Beckers A. Epidemiology and management challenges in prolactinomas. Neuroendocrinology. 2019;109(1):20-27. https://doi.org/10.1159/000497746 PMID:30731464 DOI: https://doi.org/10.1159/000497746

Olarescu NC, Perez-Rivas LG, Gatto F, et al; EYRC (ENEA Young Researcher Committee). Aggressive and Malignant Prolactinomas. Neuroendocrinology. 2019;109(1):57-69. https://doi.org/10.1159/000497205 PMID:30677777 DOI: https://doi.org/10.1159/000497205

de Laat JM, Dekkers OM, Pieterman CR, et al. Long-term natural course of pituitary tumors in patients with MEN1: results from the Dutch MEN1 study group (DMSG). J Clin Endocrinol Metab. 2015;100(9):3288-3296. https://doi.org/10.1210/JC.2015-2015 PMID:26126205 DOI: https://doi.org/10.1210/JC.2015-2015

Daly AF, Tichomirowa MA, Petrossians P, et al. Clinical characteristics and therapeutic responses in patients with germ-line AIP mutations and pituitary adenomas: an international collaborative study. J Clin Endocrinol Metab. 2010;95(11):E373-E383. https://doi.org/10.1210/jc.2009-2556 PMID:20685857 DOI: https://doi.org/10.1210/jc.2009-2556

Soto-Pedre E, Newey PJ, Bevan JS, Leese GP. Morbidity and mortality in patients with hyperprolactinaemia: the PROLEARS study. Endocr Connect. 2017;6(8):580-588. https://doi.org/10.1530/EC-17-0171 PMID:28954743 DOI: https://doi.org/10.1530/EC-17-0171

Iannone P, Coclite D, Fauci AJ, Graziano G, Napoletano AM. [Italian guidelines in accordance with the new National Guidelines System: critical issues and perspectives]. Recenti Prog Med. 2017;108(9):360-362. https://doi.org/10.1701/2745.27986 PMID:28901343

Morgano GP, Parmelli E, Amato L, et al. [GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 2: Clinical practice guidelines]. Recenti Prog Med. 2018;109(5):272-293. https://doi.org/10.1701/2902.29246 PMID:29771250

Melmed S, Casanueva FF, Hoffman AR, et al; Endocrine Society. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(2):273-288. https://doi.org/10.1210/jc.2010-1692 PMID:21296991 DOI: https://doi.org/10.1210/jc.2010-1692

Sistema Nazionale Linee Guida dell’Istituto Superiore di Sanità. Terapia dei prolattinomi. 2022. https://www.iss.it/documents/20126/8403889/LG188-AME_Terapia-prolattinomi.pdf/307919a6-d35b-b5b7-ec4c-8afc4a5eb093?t=1678805522649 (Accessed April 2023)

Verhelst J, Abs R, Maiter D, et al. Cabergoline in the treatment of hyperprolactinemia: a study in 455 patients. J Clin Endocrinol Metab. 1999;84(7):2518-2522. https://doi.org/10.1210/jcem.84.7.5810 PMID:10404830 DOI: https://doi.org/10.1210/jcem.84.7.5810

Colao A, Di Sarno A, Landi ML, et al. Macroprolactinoma shrinkage during cabergoline treatment is greater in naive patients than in patients pretreated with other dopamine agonists: a prospective study in 110 patients. J Clin Endocrinol Metab. 2000;85(6):2247-2252. https://doi.org/10.1210/jcem.85.6.6657 PMID:10852458 DOI: https://doi.org/10.1210/jc.85.6.2247

Casanueva FF, Molitch ME, Schlechte JA, et al. Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas. Clin Endocrinol (Oxf). 2006;65(2):265-273. https://doi.org/10.1111/j.1365-2265.2006.02562.x PMID:16886971 DOI: https://doi.org/10.1111/j.1365-2265.2006.02562.x

Cozzi R, Ambrosio MR, Attanasio R, et al. Italian Association of Clinical Endocrinologists (AME) and International Chapter of Clinical Endocrinology (ICCE). Position statement for clinical practice: prolactin-secreting tumors. Eur J Endocrinol. 2022;186(3):1-P33. https://doi.org/10.1530/EJE-21-0977 PMID:35000899 DOI: https://doi.org/10.1530/EJE-21-0977

Molitch ME. Dopamine resistance of prolactinomas. Pituitary. 2003;6(1):19-27. https://doi.org/10.1023/A:1026225625897 PMID:14674720 DOI: https://doi.org/10.1023/A:1026225625897

Maiter D. Management of dopamine agonist-resistant prolactinoma. Neuroendocrinology. 2019;109(1):42-50. https://doi.org/10.1159/000495775 PMID:30481756 DOI: https://doi.org/10.1159/000495775

Colao A, Di Sarno A, Cappabianca P, Di Somma C, Pivonello R, Lombardi G. Withdrawal of long-term cabergoline therapy for tumoral and nontumoral hyperprolactinemia. N Engl J Med. 2003;349(21):2023-2033. https://doi.org/10.1056/NEJMoa022657 PMID:14627787 DOI: https://doi.org/10.1056/NEJMoa022657

Zamanipoor Najafabadi AH, Zandbergen IM, de Vries F, et al. Surgery as a viable alternative first-line treatment for prolactinoma patients. A systematic review and meta-analysis. J Clin Endocrinol Metab. 2020;105(3):e32-e41. https://doi.org/10.1210/clinem/dgz144 PMID:31665485 DOI: https://doi.org/10.1210/clinem/dgz144

Tampourlou M, Trifanescu R, Paluzzi A, Ahmed SK, Karavitaki N. Therapy of endocrine disease: surgery in microprolactinomas: effectiveness and risks based on contemporary literature. Eur J Endocrinol. 2016;175(3):R89-R96. https://doi.org/10.1530/EJE-16-0087 PMID:27207245 DOI: https://doi.org/10.1530/EJE-16-0087

Roelfsema F, Biermasz NR, Pereira AM. Clinical factors involved in the recurrence of pituitary adenomas after surgical remission: a structured review and meta-analysis. Pituitary. 2012;15(1):71-83. https://doi.org/10.1007/s11102-011-0347-7 PMID:21918830 DOI: https://doi.org/10.1007/s11102-011-0347-7

Primeau V, Raftopoulos C, Maiter D. Outcomes of transsphenoidal surgery in prolactinomas: improvement of hormonal control in dopamine agonist-resistant patients. Eur J Endocrinol. 2012;166(5):779-786. https://doi.org/10.1530/EJE-11-1000 PMID:22301915 DOI: https://doi.org/10.1530/EJE-11-1000

Sheplan Olsen LJ, Robles Irizarry L, Chao ST, et al. Radiotherapy for prolactin-secreting pituitary tumors. Pituitary. 2012;15(2):135-145. https://doi.org/10.1007/s11102-011-0348-6 PMID:21948464 DOI: https://doi.org/10.1007/s11102-011-0348-6

Hung YC, Lee CC, Yang HC, et al. The benefit and risk of stereotactic radiosurgery for prolactinomas: an international multicenter cohort study. J Neurosurg. 2019;133(3):1-10. https://doi.org/10.3171/2019.4.JNS183443 PMID:31374549 DOI: https://doi.org/10.3171/2020.12.JNS183443a

Trouillas J, Delgrange E, Wierinckx A, et al. Clinical, pathological, and molecular factors of aggressiveness in lactotroph tumours. Neuroendocrinology. 2019;109(1):70-76. https://doi.org/10.1159/000499382 PMID:30943495 DOI: https://doi.org/10.1159/000499382

McCormack A, Dekkers OM, Petersenn S, et al; ESE Survey Collaborators. Treatment of aggressive pituitary tumours and carcinomas: results of a European Society of Endocrinology (ESE) survey 2016. Eur J Endocrinol. 2018;178(3):265-276. https://doi.org/10.1530/EJE-17-0933 PMID:29330228 DOI: https://doi.org/10.1530/EJE-17-0933

Drummond MF, Sculpher MJ, Claxton K, et al. Methods for the economic evaluation of health care programmes. 4th ed. Oxford University Press; 2015:253-255.

Perazzo H, Jorge MJ, Silva JC, et al. Micro-costing analysis of guideline-based treatment by direct-acting agents: the real-life case of hepatitis C management in Brazil. BMC Gastroenterol. 2017;17(1):119. https://doi.org/10.1186/s12876-017-0676-8 PMID:29169329 DOI: https://doi.org/10.1186/s12876-017-0676-8

Edwards RT, Céilleachair A, Bywater T, Hughes DA, Hutchings J. Parenting programme for parents of children at risk of developing conduct disorder: cost effectiveness analysis. BMJ. 2007;334(7595):682. https://doi.org/10.1136/bmj.39126.699421.55 PMID:17350965 DOI: https://doi.org/10.1136/bmj.39126.699421.55

Griffith GL, Edwards RT, Gray J, et al. Estimating the survival benefits gained from providing national cancer genetic services to women with a family history of breast cancer. Br J Cancer. 2004;90(10):1912-1919. https://doi.org/10.1038/sj.bjc.6601794 PMID:15138471 DOI: https://doi.org/10.1038/sj.bjc.6601794

Kinsella S. Ten lessons for micro-costing in health economics. Department of Economics, Kemmy Business School, University of Limerick; 2008.

Morris S, Devlin N, Parkin D, Spencer A. Economic analysis in healthcare. John Wiley & Sons; 2012.

Fattore G. Proposta di Linee Guida per la valutazione economica degli interventi sanitari in Italia. PharmacoEcon Ital Res Artic. 2009;11(2):83-93. https://doi.org/10.1007/BF03320660 DOI: https://doi.org/10.1007/BF03320660

Ministero della Salute M. Tariffario delle Prestazioni Specialistiche Ambulatoriali. http://www.salute.gov.it/portale/temi/p2_6.jsp?id=1767&area=programmazioneSanitariaLea&menu=lea. Accessed July 2023.

Agenzia per la Rappresentanza Negoziale delle Pubbliche Amministrazioni (ARAN). https://www.aranagenzia.it/statistiche-e-pubblicazioni/dati-statistici.html. Accessed July 2023.

Agenzia Italiana del Farmaco (AIFA). Lista di Trasparenza AIFA, Farmaci di Fascia H. https://www.aifa.gov.it/liste-farmaci-a-h. Accessed July 2023.

Agenzia Italiana del Farmaco (AIFA). Lista di Trasparenza AIFA, Farmaci di Fascia A. https://www.aifa.gov.it/liste-farmaci-a-h. Accessed July 2023.

Jethwa PR, Patel TD, Hajart AF, Eloy JA, Couldwell WT, Liu JK. Cost-effectiveness analysis of microscopic and endoscopic transsphenoidal surgery versus medical therapy in the management of microprolactinoma in the United States. World Neurosurg. 2016;87:65-76. https://doi.org/10.1016/j.wneu.2015.10.090 PMID:26548828 DOI: https://doi.org/10.1016/j.wneu.2015.10.090

Russo P, Zanuzzi M, Carletto A, Sammarco A, Romano F, Manca A. Role of economic evaluations on pricing of medicines reimbursed by the Italian National Health Service. PharmacoEconomics. 2023;41(1):107-117. https://doi.org/10.1007/s40273-022-01215-w PMID:36434415 DOI: https://doi.org/10.1007/s40273-022-01215-w

Gray AM, Clarke PM, Wolstenholme JL, Wordsworth S. Applied methods of cost-effectiveness analysis in healthcare. Vol 3. Oxford: OUP; 2010.

Baussart B, Villa C, Jouinot A, et al. Pituitary surgery as alternative to dopamine agonists treatment for microprolactinomas: a cohort study. Eur J Endocrinol. 2021;185(6):783-791. https://doi.org/10.1530/EJE-21-0293 PMID:34605772 DOI: https://doi.org/10.1530/EJE-21-0293

Casanueva FF, Barkan AL, Buchfelder M, et al; Pituitary Society, Expert Group on Pituitary Tumors. Criteria for the definition of Pituitary Tumor Centers of Excellence (PTCOE): A Pituitary Society Statement. Pituitary. 2017;20(5):489-498. https://doi.org/10.1007/s11102-017-0838-2 PMID:28884415 DOI: https://doi.org/10.1007/s11102-017-0838-2

Losa M, Mortini P, Barzaghi R, Gioia L, Giovanelli M. Surgical treatment of prolactin-secreting pituitary adenomas: early results and long-term outcome. J Clin Endocrinol Metab. 2002;87(7):3180-3186. https://doi.org/10.1210/jcem.87.7.8645 PMID:12107221 DOI: https://doi.org/10.1210/jcem.87.7.8645

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2024-01-09

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Basile, M., Valentini, I., Attanasio, R., Cozzi, R., Persichetti, A., Samperi, I., Scoppola, A., Auriemma, R. S., Menis, E. D., Esposito, F., Ferrante, E., Iatì, G., Mazzatenta, D., Maurizio Poggi, Rudà, R., Tortora, F., Cruciani, F., Mitrova, Z., Saulle, R., Vecchi, S., Cappabianca, P., Paoletta, A., Bozzao, A., Caputo, M., Doglietto, F., Ferraù, F., Lania, A. G., Laureti, S., Lello, S., Locatelli, D., Maffei, P., Minniti, G., Peri, A., Ruini, C., Settanni, F., Silvani, A., Veronese, N., Grimaldi, F., Papini, E., & Cicchetti, A. (2024). A pharmacoeconomic analysis from Italian guidelines for the management of prolactinomas. Global and Regional Health Technology Assessment, 11(1), 1–16. https://doi.org/10.33393/grhta.2024.2601

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Vol. 11 No. 1: January-December 2024

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Received 2023-05-08
Accepted 2023-11-22
Published 2024-01-09

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