Reduction of Heavy Menstrual Bleeding in Women Not Designated as Responders to Elagolix Plus Add Back Therapy for Uterine Fibroids

Abstract

Objective: To assess outcomes of women with uterine fibroids (UFs) and heavy menstrual bleeding (HMB) treated with 300 mg elagolix twice daily plus add-back therapy (E2 1 mg/NETA 0.5 mg once daily) or placebo who were not considered responders in pooled analysis of two phase 3, 6-month randomized clinical trials (Elaris UF-1 and UF-2). Methods: Responders were defined as women who met both primary end point bleeding criteria (<80 mL menstrual blood loss [MBL] during the final month and ≥50% reduction in MBL from baseline to the final month) and either completed the study or discontinued due to predefined reasons. Thus, women termed nonresponders who were analyzed in this study who met neither or one bleeding end point or met both criteria but prematurely discontinued treatment because of adverse events, perceived lack of efficacy, or required surgical or interventional treatment for UFs were analyzed in this study. This post hoc analysis assessed mean changes from baseline in MBL, as well as adverse events. Results: Among 367 women receiving elagolix with add-back with observed data, 89 (24%) were not considered responders. Within this subset, 17 (19%) women met both bleeding criteria but prematurely discontinued treatment for the reasons mentioned above, while 23 (26%) met one bleeding criterion and 49 (55%) met neither bleeding criteria, regardless of discontinuation status. Among all nonresponders, a numerical trend toward greater mean reductions in MBL was observed in those receiving elagolix with add-back, compared with placebo group nonresponders. No differences in adverse events were observed between responders and nonresponders. Conclusion: Forty of 89 (45%) women with HMB and UFs who were classified as nonresponders in the UF-1 or UF-2 trials may have had a clinically meaningful response to elagolix with add-back therapy because they met at least one of the objective bleeding criteria. Clinical Trial Registration: Clinicaltrials.gov, NCT02654054 and NCT02691494. (NEJM 2020; 382:328-340) DOI: 10.1056/NEJMoa1904351.

Keywords: GnRH antagonist; elagolix; heavy menstrual bleeding; uterine fibroids.

Conflict of interest statement

E.A.S. has been a consultant for AbbVie, Bayer, ObsEva, and Myovant. She has received research support from National Institutes for Health related to uterine fibroids (R01HD 60503 and P50HS023418) and holds a patent for Methods and Compounds for Treatment of Abnormal Uterine Bleeding (US 6440445) which has no commercial activity. She has received royalties from UpToDate and payments for the development of educational content from the Med Learning Group PER, Massachusetts Medical Society and Peer View. D.F.A. is a consultant to AbbVie, Agile Therapeutics, Bayer Healthcare, Endoceutics, Evestra, Exeltis, InnovaGyn, Lupin, Mithra, OvsEva, and TherapeuticsMD and has received research support from Actavis, Bayer Healthcare, Endoceutics, Mithra, Myovant, ObsEva, and TherapeuticsMD. He has stock in InnovaGyn and stock options from Agile Therapeutics. C.D.O. and R.L. are former AbbVie employees and have no disclosures. K.T.B. has served as a consultant to AbbVie and Bayer and served on the AbbVie Data and Safety Monitoring Committee. L.D.B. has served as a scientific advisor for AbbVie, Bayer, Allergan, Boston Scientific, Medtronic, and Karl Storz and has received research support from Bayer and royalties from UpToDate, Elsevier, and Wolters Kluwer. E.C.F. has served as a consultant to AbbVie, Natera, and CooperSurgical and served on the AbbVie Data and Safety Monitoring Committee. V.G. has served as a study investigator for AbbVie and has served as a consultant to AbbVie and Myovant. A.N.I. is a member of AbbVie's Speakers Bureau. R.L. is an AbbVie employee and holds stock or stock options. J.H.K. has served as a consultant to Empress Medical. A.A.-H. has provided consulting services to AbbVie, Allergan, Bayer, Myovant, MD Stem Cells, OBS-EVA, and Novartis and is grant funded by the National Institute of Health for fibroid-related research (R01 ES 028615-01, R01 HD 087417, R01 HD 094378, R01 HD 094380). In addition, he holds a patent for Methods for Novel Diagnostics and Therapeutics for Uterine Sarcoma (US Pat No. 9,790,562 B2).

Figures

FIG. 1.

Characteristics of women not categorized as responders to treatment. Percentages of women by treatment and response criteria. Nonresponders were defined as women who did not simultaneously meet both primary end point bleeding criteria (