Treatment of endometriosis-associated pain with elagolix, an oral GnRH antagonist

H. S. Taylor, L. C. Giudice, B. A. Lessey, M. S. Abrao, J. Kotarski, D. F. Archer, M. P. Diamond, E. Surrey, N. P. Johnson, N. B. Watts, John Christopher G. Gallagher, J. A. Simon, B. Carr, W. P. Dmowski, N. Leyland, J. P. Rowan, W. R. Duan, J. Ng, B. Schwefel, J. W. Thomas & 2 others R. I. Jain, K. Chwalisz

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Abstract

BACKGROUND Endometriosis is a chronic, estrogen-dependent condition that causes dysmenorrhea and pelvic pain. Elagolix, an oral, nonpeptide, gonadotropin-releasing hormone (GnRH) antagonist, produced partial to nearly full estrogen suppression in previous studies. METHODS We performed two similar, double-blind, randomized, 6-month phase 3 trials (Elaris Endometriosis I and II [EM-I and EM-II]) to evaluate the effects of two doses of elagolix-150 mg once daily (lower-dose group) and 200 mg twice daily (higher-dose group)-as compared with placebo in women with surgically diagnosed endometriosis and moderate or severe endometriosis-associated pain. The two primary efficacy end points were the proportion of women who had a clinical response with respect to dysmenorrhea and the proportion who had a clinical response with respect to nonmenstrual pelvic pain at 3 months. Each of these end points was measured as a clinically meaningful reduction in the pain score and a decreased or stable use of rescue analgesic agents, as recorded in a daily electronic diary. RESULTS A total of 872 women underwent randomization in Elaris EM-I and 817 in Elaris EM-II; of these women, 653 (74.9%) and 632 (77.4%), respectively, completed the intervention. At 3 months, a significantly greater proportion of women who received each elagolix dose met the clinical response criteria for the two primary end points than did those who received placebo. In Elaris EM-I, the percentage of women who had a clinical response with respect to dysmenorrhea was 46.4% in the lower-dose elagolix group and 75.8% in the higher-dose elagolix group, as compared with 19.6% in the placebo group; in Elaris EM-II, the corresponding percentages were 43.4% and 72.4%, as compared with 22.7% (P<0.001 for all comparisons). In Elaris EM-I, the percentage of women who had a clinical response with respect to nonmenstrual pelvic pain was 50.4% in the lower-dose elagolix group and 54.5% in the higher-dose elagolix group, as compared with 36.5% in the placebo group (P<0.001 for all comparisons); in Elaris EM-II, the corresponding percentages were 49.8% and 57.8%, as compared with 36.5% (P = 0.003 and P<0.001, respectively). The responses with respect to dysmenorrhea and nonmenstrual pelvic pain were sustained at 6 months. Women who received elagolix had higher rates of hot flushes (mostly mild or moderate), higher levels of serum lipids, and greater decreases from baseline in bone mineral density than did those who received placebo; there were no adverse endometrial findings. CONCLUSIONS Both higher and lower doses of elagolix were effective in improving dysmenorrhea and nonmenstrual pelvic pain during a 6-month period in women with endometriosis-associated pain. The two doses of elagolix were associated with hypoestrogenic adverse effects.

Original languageEnglish (US)
Pages (from-to)28-40
Number of pages13
JournalNew England Journal of Medicine
Volume377
Issue number1
DOIs
StatePublished - Jul 6 2017

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Hormone Antagonists
Endometriosis
Gonadotropin-Releasing Hormone
Pain
Dysmenorrhea
Pelvic Pain
Placebos
Therapeutics
Estrogens
elagolix
Random Allocation
Bone Density
Analgesics

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Taylor, H. S., Giudice, L. C., Lessey, B. A., Abrao, M. S., Kotarski, J., Archer, D. F., ... Chwalisz, K. (2017). Treatment of endometriosis-associated pain with elagolix, an oral GnRH antagonist. New England Journal of Medicine, 377(1), 28-40. https://doi.org/10.1056/NEJMoa1700089

Treatment of endometriosis-associated pain with elagolix, an oral GnRH antagonist. / Taylor, H. S.; Giudice, L. C.; Lessey, B. A.; Abrao, M. S.; Kotarski, J.; Archer, D. F.; Diamond, M. P.; Surrey, E.; Johnson, N. P.; Watts, N. B.; Gallagher, John Christopher G.; Simon, J. A.; Carr, B.; Dmowski, W. P.; Leyland, N.; Rowan, J. P.; Duan, W. R.; Ng, J.; Schwefel, B.; Thomas, J. W.; Jain, R. I.; Chwalisz, K.

In: New England Journal of Medicine, Vol. 377, No. 1, 06.07.2017, p. 28-40.

Research output: Contribution to journalArticle

Taylor, HS, Giudice, LC, Lessey, BA, Abrao, MS, Kotarski, J, Archer, DF, Diamond, MP, Surrey, E, Johnson, NP, Watts, NB, Gallagher, JCG, Simon, JA, Carr, B, Dmowski, WP, Leyland, N, Rowan, JP, Duan, WR, Ng, J, Schwefel, B, Thomas, JW, Jain, RI & Chwalisz, K 2017, 'Treatment of endometriosis-associated pain with elagolix, an oral GnRH antagonist', New England Journal of Medicine, vol. 377, no. 1, pp. 28-40. https://doi.org/10.1056/NEJMoa1700089
Taylor HS, Giudice LC, Lessey BA, Abrao MS, Kotarski J, Archer DF et al. Treatment of endometriosis-associated pain with elagolix, an oral GnRH antagonist. New England Journal of Medicine. 2017 Jul 6;377(1):28-40. https://doi.org/10.1056/NEJMoa1700089
Taylor, H. S. ; Giudice, L. C. ; Lessey, B. A. ; Abrao, M. S. ; Kotarski, J. ; Archer, D. F. ; Diamond, M. P. ; Surrey, E. ; Johnson, N. P. ; Watts, N. B. ; Gallagher, John Christopher G. ; Simon, J. A. ; Carr, B. ; Dmowski, W. P. ; Leyland, N. ; Rowan, J. P. ; Duan, W. R. ; Ng, J. ; Schwefel, B. ; Thomas, J. W. ; Jain, R. I. ; Chwalisz, K. / Treatment of endometriosis-associated pain with elagolix, an oral GnRH antagonist. In: New England Journal of Medicine. 2017 ; Vol. 377, No. 1. pp. 28-40.
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abstract = "BACKGROUND Endometriosis is a chronic, estrogen-dependent condition that causes dysmenorrhea and pelvic pain. Elagolix, an oral, nonpeptide, gonadotropin-releasing hormone (GnRH) antagonist, produced partial to nearly full estrogen suppression in previous studies. METHODS We performed two similar, double-blind, randomized, 6-month phase 3 trials (Elaris Endometriosis I and II [EM-I and EM-II]) to evaluate the effects of two doses of elagolix-150 mg once daily (lower-dose group) and 200 mg twice daily (higher-dose group)-as compared with placebo in women with surgically diagnosed endometriosis and moderate or severe endometriosis-associated pain. The two primary efficacy end points were the proportion of women who had a clinical response with respect to dysmenorrhea and the proportion who had a clinical response with respect to nonmenstrual pelvic pain at 3 months. Each of these end points was measured as a clinically meaningful reduction in the pain score and a decreased or stable use of rescue analgesic agents, as recorded in a daily electronic diary. RESULTS A total of 872 women underwent randomization in Elaris EM-I and 817 in Elaris EM-II; of these women, 653 (74.9{\%}) and 632 (77.4{\%}), respectively, completed the intervention. At 3 months, a significantly greater proportion of women who received each elagolix dose met the clinical response criteria for the two primary end points than did those who received placebo. In Elaris EM-I, the percentage of women who had a clinical response with respect to dysmenorrhea was 46.4{\%} in the lower-dose elagolix group and 75.8{\%} in the higher-dose elagolix group, as compared with 19.6{\%} in the placebo group; in Elaris EM-II, the corresponding percentages were 43.4{\%} and 72.4{\%}, as compared with 22.7{\%} (P<0.001 for all comparisons). In Elaris EM-I, the percentage of women who had a clinical response with respect to nonmenstrual pelvic pain was 50.4{\%} in the lower-dose elagolix group and 54.5{\%} in the higher-dose elagolix group, as compared with 36.5{\%} in the placebo group (P<0.001 for all comparisons); in Elaris EM-II, the corresponding percentages were 49.8{\%} and 57.8{\%}, as compared with 36.5{\%} (P = 0.003 and P<0.001, respectively). The responses with respect to dysmenorrhea and nonmenstrual pelvic pain were sustained at 6 months. Women who received elagolix had higher rates of hot flushes (mostly mild or moderate), higher levels of serum lipids, and greater decreases from baseline in bone mineral density than did those who received placebo; there were no adverse endometrial findings. CONCLUSIONS Both higher and lower doses of elagolix were effective in improving dysmenorrhea and nonmenstrual pelvic pain during a 6-month period in women with endometriosis-associated pain. The two doses of elagolix were associated with hypoestrogenic adverse effects.",
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TY - JOUR

T1 - Treatment of endometriosis-associated pain with elagolix, an oral GnRH antagonist

AU - Taylor, H. S.

AU - Giudice, L. C.

AU - Lessey, B. A.

AU - Abrao, M. S.

AU - Kotarski, J.

AU - Archer, D. F.

AU - Diamond, M. P.

AU - Surrey, E.

AU - Johnson, N. P.

AU - Watts, N. B.

AU - Gallagher, John Christopher G.

AU - Simon, J. A.

AU - Carr, B.

AU - Dmowski, W. P.

AU - Leyland, N.

AU - Rowan, J. P.

AU - Duan, W. R.

AU - Ng, J.

AU - Schwefel, B.

AU - Thomas, J. W.

AU - Jain, R. I.

AU - Chwalisz, K.

PY - 2017/7/6

Y1 - 2017/7/6

N2 - BACKGROUND Endometriosis is a chronic, estrogen-dependent condition that causes dysmenorrhea and pelvic pain. Elagolix, an oral, nonpeptide, gonadotropin-releasing hormone (GnRH) antagonist, produced partial to nearly full estrogen suppression in previous studies. METHODS We performed two similar, double-blind, randomized, 6-month phase 3 trials (Elaris Endometriosis I and II [EM-I and EM-II]) to evaluate the effects of two doses of elagolix-150 mg once daily (lower-dose group) and 200 mg twice daily (higher-dose group)-as compared with placebo in women with surgically diagnosed endometriosis and moderate or severe endometriosis-associated pain. The two primary efficacy end points were the proportion of women who had a clinical response with respect to dysmenorrhea and the proportion who had a clinical response with respect to nonmenstrual pelvic pain at 3 months. Each of these end points was measured as a clinically meaningful reduction in the pain score and a decreased or stable use of rescue analgesic agents, as recorded in a daily electronic diary. RESULTS A total of 872 women underwent randomization in Elaris EM-I and 817 in Elaris EM-II; of these women, 653 (74.9%) and 632 (77.4%), respectively, completed the intervention. At 3 months, a significantly greater proportion of women who received each elagolix dose met the clinical response criteria for the two primary end points than did those who received placebo. In Elaris EM-I, the percentage of women who had a clinical response with respect to dysmenorrhea was 46.4% in the lower-dose elagolix group and 75.8% in the higher-dose elagolix group, as compared with 19.6% in the placebo group; in Elaris EM-II, the corresponding percentages were 43.4% and 72.4%, as compared with 22.7% (P<0.001 for all comparisons). In Elaris EM-I, the percentage of women who had a clinical response with respect to nonmenstrual pelvic pain was 50.4% in the lower-dose elagolix group and 54.5% in the higher-dose elagolix group, as compared with 36.5% in the placebo group (P<0.001 for all comparisons); in Elaris EM-II, the corresponding percentages were 49.8% and 57.8%, as compared with 36.5% (P = 0.003 and P<0.001, respectively). The responses with respect to dysmenorrhea and nonmenstrual pelvic pain were sustained at 6 months. Women who received elagolix had higher rates of hot flushes (mostly mild or moderate), higher levels of serum lipids, and greater decreases from baseline in bone mineral density than did those who received placebo; there were no adverse endometrial findings. CONCLUSIONS Both higher and lower doses of elagolix were effective in improving dysmenorrhea and nonmenstrual pelvic pain during a 6-month period in women with endometriosis-associated pain. The two doses of elagolix were associated with hypoestrogenic adverse effects.

AB - BACKGROUND Endometriosis is a chronic, estrogen-dependent condition that causes dysmenorrhea and pelvic pain. Elagolix, an oral, nonpeptide, gonadotropin-releasing hormone (GnRH) antagonist, produced partial to nearly full estrogen suppression in previous studies. METHODS We performed two similar, double-blind, randomized, 6-month phase 3 trials (Elaris Endometriosis I and II [EM-I and EM-II]) to evaluate the effects of two doses of elagolix-150 mg once daily (lower-dose group) and 200 mg twice daily (higher-dose group)-as compared with placebo in women with surgically diagnosed endometriosis and moderate or severe endometriosis-associated pain. The two primary efficacy end points were the proportion of women who had a clinical response with respect to dysmenorrhea and the proportion who had a clinical response with respect to nonmenstrual pelvic pain at 3 months. Each of these end points was measured as a clinically meaningful reduction in the pain score and a decreased or stable use of rescue analgesic agents, as recorded in a daily electronic diary. RESULTS A total of 872 women underwent randomization in Elaris EM-I and 817 in Elaris EM-II; of these women, 653 (74.9%) and 632 (77.4%), respectively, completed the intervention. At 3 months, a significantly greater proportion of women who received each elagolix dose met the clinical response criteria for the two primary end points than did those who received placebo. In Elaris EM-I, the percentage of women who had a clinical response with respect to dysmenorrhea was 46.4% in the lower-dose elagolix group and 75.8% in the higher-dose elagolix group, as compared with 19.6% in the placebo group; in Elaris EM-II, the corresponding percentages were 43.4% and 72.4%, as compared with 22.7% (P<0.001 for all comparisons). In Elaris EM-I, the percentage of women who had a clinical response with respect to nonmenstrual pelvic pain was 50.4% in the lower-dose elagolix group and 54.5% in the higher-dose elagolix group, as compared with 36.5% in the placebo group (P<0.001 for all comparisons); in Elaris EM-II, the corresponding percentages were 49.8% and 57.8%, as compared with 36.5% (P = 0.003 and P<0.001, respectively). The responses with respect to dysmenorrhea and nonmenstrual pelvic pain were sustained at 6 months. Women who received elagolix had higher rates of hot flushes (mostly mild or moderate), higher levels of serum lipids, and greater decreases from baseline in bone mineral density than did those who received placebo; there were no adverse endometrial findings. CONCLUSIONS Both higher and lower doses of elagolix were effective in improving dysmenorrhea and nonmenstrual pelvic pain during a 6-month period in women with endometriosis-associated pain. The two doses of elagolix were associated with hypoestrogenic adverse effects.

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