Cost–effectiveness of elagolix versus leuprolide acetate for treating moderate-to-severe endometriosis pain in the USA
Abstract
Aim: To assess the cost–effectiveness of elagolix versus leuprolide acetate in women with moderate to severe endometriosis pain. Methods: A Markov model was developed. The efficacy of leuprolide acetate was derived from statistical prediction models using elagolix trial data. Model inputs were extracted from Phase III clinical trials and published literature. Results: Compared with leuprolide acetate, elagolix generated positive net monetary benefit (NMB) assuming a payer's willingness-to-pay threshold of US$100,000 per quality-adjusted life year over a 1-year time horizon: US$5660 for elagolix 150 mg and US$6443 for elagolix 200 mg. The 2-year NMBs were also positive. Conclusion: Elagolix was cost effective versus leuprolide acetate in the management of moderate to severe endometriosis pain over 1- and 2-year time horizons. Results were robust in sensitivity analyses.
Supplementary Material
File (supplementaryappendix.docx)
- Download
- 105.80 KB
References
Papers of special note have been highlighted as: • of interest
1.
Parasar P, Ozcan P, Terry KL. Endometriosis: epidemiology, diagnosis and clinical management. Curr. Obstet. Gynecol. Rep. 6(1), 34–41 (2017).
2.
Fuldeore MJ, Soliman AM. Prevalence and symptomatic burden of diagnosed endometriosis in the United States: national estimates from a cross-sectional survey of 59,411 women. Gynecol. Obst. Invest. 82(5), 453–461 (2017).
3.
Ferrero S, Arena E, Morando A, Remorgida V. Prevalence of newly diagnosed endometriosis in women attending the general practitioner. Int. J. Gynecol. Obstet. 110(3), 203–207 (2010).
4.
Eskenazi B, Warner ML. Epidemiology of endometriosis. Obstet. Gynecol. Clin. North Am. 24(2), 235–258 (1997).
5.
Practice bulletin no. 114: management of endometriosis. Obstet. Gynecol. 116(1), 223–236 (2010).
6.
Nnoaham KE, Hummelshoj L, Webster P et al. Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries. Fertil. Steril. 96(2), 366–373.e368 (2011).
7.
Kvaskoff M, Mu F, Terry KL et al. Endometriosis: a high-risk population for major chronic diseases? Hum. Reprod. Update 21(4), 500–516 (2015).
8.
Soliman AM, Coyne KS, Gries KS, Castelli-Haley J, Snabes MC, Surrey ES. The effect of endometriosis symptoms on absenteeism and presenteeism in the workplace and at home. J. Manag. Care Specialty Pharm. 23(7), 745–754 (2017).
• This US claims data study assessed the burden of endometriosis pain symptoms on productivity loss both in the workplace (presenteeism and absenteeism) and at home.
9.
Soliman AM, Yang H, Du EX, Kelley C, Winkel C. The direct and indirect costs associated with endometriosis: a systematic literature review. Hum. Reprod. 31(4), 712–722 (2016).
10.
Simoens S, Dunselman G, Dirksen C et al. The burden of endometriosis: costs and quality of life of women with endometriosis and treated in referral centres. Hum. Reprod. 27(5), 1292–1299 (2012).
11.
Mirkin D, Murphy-Barron C, Iwasaki K. Actuarial analysis of private payer administrative claims data for women with endometriosis. J. Manag. Care Pharm. 13(3), 262–272 (2007).
12.
Fuldeore M, Yang H, Du EX, Soliman AM, Wu EQ, Winkel C. Healthcare utilization and costs in women diagnosed with endometriosis before and after diagnosis: a longitudinal analysis of claims databases. Fertil. Steril. 103(1), 163–171 (2015).
13.
Soliman AM, Surrey E, Bonafede M, Nelson JK, Castelli-Haley J. Real-world evaluation of direct and indirect economic burden among endometriosis patients in the United States. Adv. Ther. 35(3), 408–423 (2018).
14.
Guerriero S, Condous G, Van Den Bosch T et al. Systematic approach to sonographic evaluation of the pelvis in women with suspected endometriosis, including terms, definitions and measurements: a consensus opinion from the International Deep Endometriosis Analysis (IDEA) group. Ultrasound Obstet. Gynecol. 48(3), 318–332 (2016).
15.
Giudice LC. Clinical practice. Endometriosis. N. Engl. J. Med. 362(25), 2389–2398 (2010).
16.
Ferrero S, Barra F, Leone Roberti Maggiore U. Current and emerging therapeutics for the management of endometriosis. Drugs 78(10), 995–1012 (2018).
17.
Abbvie. Lupron Depot: highlights of prescribing information (2018). www.accessdata.fda.gov/drugsatfda_docs/label/2018/020708s035lbl.pdf.
18.
Hornstein MD, Surrey ES, Weisberg GW, Casino LA. Leuprolide acetate depot and hormonal add-back in endometriosis: a 12-month study. Lupron Add-Back Study Group. Obstet. Gynecol. 91(1), 16–24 (1998).
• This is the pivotal Phase III leuprolide acetate (Lupron) trial comparing leuprolide acetate alone and leuprolide acetate with three hormonal add-back regimens.
19.
Collinet P, Fritel X, Revel-Delhom C et al. Management of endometriosis: CNGOF/HAS clinical practice guidelines – short version. J. Gynecol. Obstet. Hum. Reprod. 47(7), 265–274 (2018).
20.
US FDA. Novel drug approvals for 2018 (2018). www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/ucm592464.htm.
21.
Abbvie. Orilissa (elagolix): highlights of prescribing information (2018). www.accessdata.fda.gov/drugsatfda_docs/label/2018/210450s000lbl.pdf.
22.
Taylor HS, Giudice LC, Lessey BA et al. Treatment of endometriosis-associated pain with elagolix, an oral GnRH antagonist. N. Engl. J. Med. 377(1), 28–40 (2017).
• This is the pivotal elagolix Phase III trials comparing elagolix to placebo in women with moderate to severe pain symptoms.
23.
Institute for Clinical and Economic Review, New England Comparative Effectiveness Public Advisory Council. Endometriosis: final evidence report (2018). https://icer-review.org/material/endo-final-evidence-report/.
24.
Wyrwich KW, O'Brien CF, Soliman AM, Chwalisz K. Development and validation of the endometriosis daily pain impact diary items to assess dysmenorrhea and nonmenstrual pelvic pain. Reprod. Sci. 25(11), 1567–1576 (2018).
25.
Schlaff WD, Carson SA, Luciano A, Ross D, Bergqvist A. Subcutaneous injection of depot medroxyprogesterone acetate compared with leuprolide acetate in the treatment of endometriosis-associated pain. Fertil. Steril. 85(2), 314–325 (2006).
• This is one of two Phase III trials comparing depot medroxyprogesterone acetate to leuprolide acetate (Lupron) in women with moderate to severe pain symptoms.
26.
Crosignani PG, Luciano A, Ray A, Bergqvist A. Subcutaneous depot medroxyprogesterone acetate versus leuprolide acetate in the treatment of endometriosis-associated pain. Hum. Reprod. 21(1), 248–256 (2006).
• This is one of two Phase III trials comparing depot medroxyprogesterone acetate to leuprolide acetate (Lupron) in women with moderate to severe pain symptoms.
27.
Biberoglu KO, Behrman SJ. Dosage aspects of danazol therapy in endometriosis: short-term and long-term effectiveness. Am. J. Obstet. Gynecol. 139(6), 645–654 (1981).
28.
Deal LS, Dibenedetti DB, Williams VS, Fehnel SE. The development and validation of the daily electronic Endometriosis Pain and Bleeding Diary. Health Qual. Life Outcomes 8, 64 (2010).
29.
Fleurence RL, Hollenbeak CS. Rates and probabilities in economic modelling: transformation, translation and appropriate application. PharmacoEconomics 25(1), 3–6 (2007).
30.
Cheewadhanaraks S. Cumulative recurrence rates of endometriosis-associated pain after long-term intramuscular depot medroxyprogesterone acetate therapy. J. Med. Assoc. Thai. 96(2), 140–143 (2013).
31.
Soliman AM, Bonafede M, Farr AM, Castelli-Haley J, Winkel C. Analysis of adherence, persistence, and surgery among endometriosis patients treated with leuprolide acetate plus norethindrone acetate add-back therapy. J. Manag. Care Specialty Pharm. 22(5), 573–587 (2016).
32.
Soliman AM, Du EX, Yang H, Wu EQ, Haley JC. Retreatment rates among endometriosis patients undergoing hysterectomy or laparoscopy. J. Women's Health 26(6), 644–654 (2017).
33.
Surrey ES, Soliman AM, Yang H, Du EX, Su B. Treatment patterns, complications, and health care utilization among endometriosis patients undergoing a laparoscopy or a hysterectomy: a retrospective claims analysis. Adv. Ther. 34(11), 2436–2451 (2017).
34.
Chapron C, Querleu D, Bruhat MA et al. Surgical complications of diagnostic and operative gynaecological laparoscopy: a series of 29,966 cases. Hum. Reprod. 13(4), 867–872 (1998).
35.
Maresh MJ, Metcalfe MA, Mcpherson K et al. The VALUE national hysterectomy study: description of the patients and their surgery. BJOG 109(3), 302–312 (2002).
36.
Arias E, Heron M, Xu J. United States life tables, 2014. Natl. Vital Stat. Rep. 66(4), (2017).
37.
Abbvie. Data on file: H18.DoF.030 (2018).
38.
Looker AC, Sarafrazi Isfahani N, Fan B, Shepherd JA. FRAX-based estimates of 10-year probability of hip and major osteoporotic fracture among adults aged 40 and over: United States, 2013 and 2014. Natl Health Stat. Rep. 103, 1–16 (2017).
39.
FRAX: Fracture Risk Assessment Tool – Calculation Tool (2018). www.sheffield.ac.uk/FRAX/tool.aspx?country=9.
40.
Surrey E, Taylor HS, Giudice L et al. Long-term outcomes of elagolix in women with endometriosis: results from two extension studies. Obstet. Gynecol. 132(1), 147–160 (2018).
• This paper presented the long-term results of the two pivotal elagolix Phase III trials’ 6-month extension studies, after 12 months of total continuous treatment.
41.
Roberts TE, Tsourapas A, Middleton LJ et al. Hysterectomy, endometrial ablation, and levonorgestrel releasing intrauterine system (Mirena) for treatment of heavy menstrual bleeding: cost–effectiveness analysis. BMJ 342, d2202 (2011).
42.
Abbott J, Hawe J, Hunter D, Holmes M, Finn P, Garry R. Laparoscopic excision of endometriosis: a randomized, placebo-controlled trial. Fertil. Steril. 82(4), 878–884 (2004).
43.
Abbvie. Data on file: H18.DoF.034 (2018).
44.
Lux MP, Reichelt C, Karnon J et al. Cost–benefit analysis of endocrine therapy in the adjuvant setting for postmenopausal patients with hormone receptor-positive breast cancer, based on survival data and future prices for generic drugs in the context of the german health care system. Breast Care (Basel, Switzerland) 6(5), 381–389 (2011).
45.
Sapin C, Fantino B, Nowicki M-L, Kind P. Usefulness of EQ-5D in assessing health status in primary care patients with major depressive disorder. Health Qual. Life Outcomes 2, 20–20 (2004).
46.
Sullivan PW, Lawrence WF, Ghushchyan V. A national catalog of preference-based scores for chronic conditions in the United States. Med. Care 43(7), 736–749 (2005).
47.
Maniadakis N, Kourlaba G, Mougiakos T, Chatzimanolis I, Jonsson L. Economic evaluation of agomelatine relative to other antidepressants for treatment of major depressive disorders in Greece. BMC Health Serv. Res. 13, 173 (2013).
48.
Matza LS, Boye KS, Yurgin N et al. Utilities and disutilities for type 2 diabetes treatment-related attributes. Qual. Life Res. 16(7), 1251–1265 (2007).
49.
Truven Health Analytics. Micromedex Red Book Online Search. (2018).
50.
American Medical Association. CPT/Medicare Payment Search. www.ama-assn.org/practice-management/cpt-current-procedural-terminology.
51.
Medical Expenditure Panel Survey (2014).
52.
Foley K, Foley D, Johnson BH. Healthcare resource utilization and expenditures of women diagnosed with hypoactive sexual desire disorder. J. Med. Econ. 13(4), 583–590 (2010).
53.
Sarrel P, Portman D, Lefebvre P et al. Incremental direct and indirect costs of untreated vasomotor symptoms. Menopause 22(3), 260–266 (2015).
54.
Piwko C, Koren G, Babashov V, Vicente C, Einarson TR. Economic burden of nausea and vomiting of pregnancy in the USA. J. Pop. Therapeut. Clin. Pharmacol. 20(2), e149–e160 (2013).
55.
Kim DD, Basu A. Estimating the medical care costs of obesity in the United States: systematic review, meta-analysis, and empirical analysis. Value Health 19(5), 602–613 (2016).
56.
Winkel CA. Modeling of medical and surgical treatment costs of chronic pelvic pain: new paradigms for making clinical decisions. Am. J. Manag. Care 5(5 Suppl.), S276–S290 (1999).
57.
Soliman AM, Taylor H, Bonafede M, Nelson JK, Castelli-Haley J. Incremental direct and indirect cost burden attributed to endometriosis surgeries in the United States. Fertil. Steril. 107(5), 1181–1190.e1182 (2017).
• This retrospective cohort study quantified the incremental direct (healthcare) and indirect (absenteeism and short-/long-term disability) cost burden of endometriosis surgeries in the US.
58.
Agency for Healthcare Research and Quality. Healthcare cost and utilization project (2015). http://hcupnet.ahrq.gov.
59.
Consumer Price Index for All Urban Consumers (2017).
60.
Lipscomb J, Weinstein MC, Torrance GW, United States Public Health Service Panel on cost–effectiveness in health and medicine. Time preference. In: Cost–Effectiveness In Health and Medicine. Gold MR, Siegel JE, Russell LB, Weinstein MC (Eds). Oxford University Press, USA, 214–246 (1996).
61.
National Institute for Health and Care Excellence. Endometriosis: diagnosis and management. NICE Guideline [NG73] (2017).
62.
Wu B, Yang Z, Tobe RG, Wang Y. Medical therapy for preventing recurrent endometriosis after conservative surgery: a cost–effectiveness analysis. BJOG 125(4), 469–477 (2018).
63.
Sanghera S, Barton P, Bhattacharya S, Horne AW, Roberts TE. Pharmaceutical treatments to prevent recurrence of endometriosis following surgery: a model-based economic evaluation. BMJ Open 6(4), (2016).
64.
Poulos C, Soliman AM, Renz C, Posner J, Agarwal SK. A discrete-choice experiment study of patient preferences for treatments for endometriosis-associated pain. Presented at: American Society for Reproductive Medicine 2018 Scientific Congress & Expo. AL, USA, 26–10 October (2018).
Information & Authors
Information
Published In
Copyright
© 2019 Medicus Economics, LLC.
History
Received: 14 November 2018
Accepted: 8 January 2019
Published online: 6 February 2019
Keywords:
Topics
Authors
Metrics & Citations
Metrics
Article Usage
Article usage data only available from February 2023. Historical article usage data, showing the number of article downloads, is available upon request.
Citations
How to Cite
Cost–effectiveness of elagolix versus leuprolide acetate for treating moderate-to-severe endometriosis pain in the USA. (2019) Journal of Comparative Effectiveness Research. DOI: 10.2217/cer-2018-0124
Export citation
Select the citation format you wish to export for this article or chapter.
Citing Literature
- Magdalena Gniadek, Alina Porubenska, Karolina Pełka, Zuzanna Rzepkowska, Jerzy Florjański, Endometriosis-Associated Infertility: A Review of Pathophysiological Mechanisms and Current Treatment Strategies, Journal of Clinical Medicine, 10.3390/jcm15114297, 15, 11, (4297), (2026).
- Sunita Tandulwadkar, Basab Mukherjee, Chaitanya Ganpule, Madhuri Patel, Subash Mallya, P.M. Gopinath, Brajbala Tiwari, Expert opinion by Federation of Obstetric and Gynaecological Societies of India on elagolix − Redefining the endometriosis therapy landscape, European Journal of Obstetrics & Gynecology and Reproductive Biology, 10.1016/j.ejogrb.2026.115115, 322, (115115), (2026).
- Yihan Xu, Carley Prentice, Sergio Torres-Rueda, András Meczner, Jan Multmeier, Aidan Wickham, Laura Kelly, Anna Klepchukova, Heorhi Stsefanovich, Liudmila Zhaunova, Economic evaluation of a digital symptom checker for endometriosis using a Markov decision process model, npj Digital Medicine, 10.1038/s41746-025-02332-4, 9, 1, (2026).
- Lan Luo, Yonglin Zhang, Li Zhang, Senguo Yang, Tian Zhou, Ke Luo, Shu Liu, Ovarian escape in premenopausal breast cancer: Challenges and strategies for optimizing hormone suppression, Cancer Treatment Reviews, 10.1016/j.ctrv.2025.102970, 139, (102970), (2025).
- Madhuri Patel, Recent Trends in Medical Management of Endometriosis, The Journal of Obstetrics and Gynecology of India, 10.1007/s13224-024-02097-y, 74, 6, (479-483), (2024).
- Jessica Ottolina, Roberta Villanacci, Sara D’Alessandro, Xuemin He, Giorgia Grisafi, Stefano Maria Ferrari, Massimo Candiani, Endometriosis and Adenomyosis: Modern Concepts of Their Clinical Outcomes, Treatment, and Management, Journal of Clinical Medicine, 10.3390/jcm13143996, 13, 14, (3996), (2024).
- Mong‐Jen Chen, Patrick Marroum, Yi‐Lin Chiu, Melina Neenan, Nael M. Mostafa, Mohamad Shebley, Bioequivalence of Elagolix/Estradiol/Norethindrone Acetate Fixed‐Dose Combination Product: Phase 1 Results in Healthy Pre‐ and Postmenopausal Women, Clinical Pharmacology in Drug Development, 10.1002/cpdd.1399, 13, 6, (601-610), (2024).
- Essam Othman, Ayman Al-Hendy, Radwa Mostafa, Cornelis Lambalk, Velja Mijatovic, Oral GnRH Antagonists in Combination with Estradiol and Norethindrone Acetate for Pain Relief Associated with Endometriosis: A Review of Evidence of a Novel Class of Hormonal Agents, International Journal of Women's Health, 10.2147/IJWH.S442357, Volume 16, (309-321), (2024).
- Josep Darbà, Alicia Marsà, Economic Implications of Endometriosis: A Review, PharmacoEconomics, 10.1007/s40273-022-01211-0, 40, 12, (1143-1158), (2022).
- Jacques Donnez, Marie-Madeleine Dolmans, GnRH Antagonists with or without Add-Back Therapy: A New Alternative in the Management of Endometriosis?, International Journal of Molecular Sciences, 10.3390/ijms222111342, 22, 21, (11342), (2021).