Elagolix for endometriosis: all that glitters is not gold

• Published in: Human reproduction (Oxford) Vol. 34; no. 2; pp. 193 - 199
• Main Authors: Vercellini, Paolo, Viganò, Paola, Barbara, Giussy, Buggio, Laura, Somigliana, Edgardo
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-02-2019
• Subjects: GnRH agonists; oral contraceptives; progestogens; endometriosis; GnRH antagonists; pelvic pain; medical therapy
• ISSN: 0268-1161; 1460-2350
• DOI: 10.1093/humrep/dey368

Abstract
Elagolix, an orally active non-peptidic GnRH antagonist, has been approved by the Food and Drug Administration for the management of moderate to severe pain associated with endometriosis. As the degree of ovarian suppression obtained with elagolix is dose-dependent, pain relief may be achieved by modulating the level of hypo-oestrogenism while limiting side effects. Elagolix may thus be considered a novelty in terms of its endocrine and pharmacological properties but not for its impact on the pathogenic mechanisms of endometriosis, as the target of this new drug is, yet again, alteration of the hormonal milieu. Given the oestrogen-dependent nature of endometriosis, a reduction of side effects may imply a proportionate decrease in pain relief. Furthermore, if low elagolix doses are used, ovulation is not consistently inhibited, and patients should use non-hormonal contraceptive systems and perform serial urine pregnancy tests to rule out unplanned conception during periods of treatment-induced amenorrhoea. If high elagolix doses are used to control severe pain for long periods of time, add-back therapies should be added, similar to that prescribed when using GnRH agonists. To date, the efficacy of elagolix has only been demonstrated in placebo-controlled explanatory trials. Pragmatic trials comparing elagolix with low-dose hormonal contraceptives and progestogens should be planned to verify the magnitude of the incremental benefit, if any, of this GnRH antagonist over currently used standard treatments. The price of elagolix may impact on patient adherence and, hence, on clinical effectiveness. In the USA, the manufacturer AbbVie Inc. priced elagolix (OrilissaTM) at around $10 000 a year, i.e. $845 per month. When faced with unaffordable treatments, some patients may choose to forego care. If national healthcare systems are funded by the tax payer, the approval and the use of a new costly drug to treat a chronic condition, such as endometriosis, means that some finite financial resources will be diverted from other areas, or that similar patients will not receive the same level of care. Thus, defining the overall 'value' of a new drug for endometriosis also has ethical implications, and trade-offs between health outcomes and costs should be carefully weighed up.