Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist
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Citações na Scopus
339
Tipo de produção
article
Data de publicação
2017
Título da Revista
ISSN da Revista
Título do Volume
Editora
MASSACHUSETTS MEDICAL SOC
Autores
TAYLOR, H. S.
GIUDICE, L. C.
LESSEY, B. A.
KOTARSKI, J.
ARCHER, D. F.
DIAMOND, M. P.
SURREY, E.
JOHNSON, N. P.
WATTS, N. B.
Citação
NEW ENGLAND JOURNAL OF MEDICINE, v.377, n.1, p.28-40, 2017
Resumo
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. (Funded by AbbVie; Elaris EM-I and EM-II ClinicalTrials.gov numbers, NCT01620528 and NCT01931670.)
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Referências
- BARBIERI RL, 1992, AM J OBSTET GYNECOL, V166, P740, DOI 10.1016/0002-9378(92)91706-G
- Brosens JJ, 2012, MOL CELL ENDOCRINOL, V358, P145, DOI 10.1016/j.mce.2012.02.023
- Brown J., 2010, COCHRANE DB SYST REV, V12, DOI 10.1002/14651858.CD008475.PUB2
- Bulun SE, 2002, ANN NY ACAD SCI, V955, P75, DOI 10.1111/j.1749-6632.2002.tb02767.x
- Bulun SE, 2009, NEW ENGL J MED, V360, P268, DOI 10.1056/NEJMra0804690
- Burney RO, 2007, ENDOCRINOLOGY, V148, P3814, DOI 10.1210/en.2006-1692
- Carr B, 2013, J ENDOMETR PELVIC PA, V5, P105, DOI 10.5301/je.5000157
- Carr B, 2014, REPROD SCI, V21, P1341, DOI 10.1177/1933719114549848
- Diamond MP, 2014, REPROD SCI, V21, P363, DOI 10.1177/1933719113497292
- Dragoman MV, 2016, CONTRACEPTION, V94, P202, DOI 10.1016/j.contraception.2016.02.003
- Du HL, 2007, STEM CELLS, V25, P2082, DOI 10.1634/stemcells.2006-0828
- Farrar JT, 2001, PAIN, V94, P149, DOI 10.1016/S0304-3959(01)00349-9
- Gao X, 2006, FERTIL STERIL, V86, P1561, DOI 10.1016/j.fertnstert.2006.06.015
- Giudice LC, 2010, NEW ENGL J MED, V362, P2389, DOI 10.1056/NEJMcp1000274
- Guo SW, 2009, HUM REPROD UPDATE, V15, P441, DOI 10.1093/humupd/dmp007
- Gylfason JT, 2010, AM J EPIDEMIOL, V172, P237, DOI 10.1093/aje/kwq143
- Hornstein MD, 1998, OBSTET GYNECOL, V91, P16, DOI 10.1016/S0029-7844(97)00620-0
- Jacobson TA, 2014, J CLIN LIPIDOL, V8, P473, DOI 10.1016/j.jacl.2014.07.007
- Johnson NP, 2013, HUM REPROD, V28, P1552, DOI 10.1093/humrep/det050
- Leyland Nicholas, 2010, J Obstet Gynaecol Can, V32, pS1
- Maggi R, 2016, HUM REPROD UPDATE, V22, P358, DOI 10.1093/humupd/dmv059
- Missmer SA, 2004, OBSTET GYNECOL, V104, P965, DOI 10.1097/01.AOG.0000142714.54857.f8
- Mu F, 2016, CIRC-CARDIOVASC QUAL, V9, P257, DOI 10.1161/CIRCOUTCOMES.115.002224
- Ng J, 2017, J CLIN ENDOCR METAB, V102, P1683, DOI 10.1210/jc.2016-3845
- Nnoaham KE, 2011, FERTIL STERIL, V96, P366, DOI 10.1016/j.fertnstert.2011.05.090
- Ofer Adam, 2016, Am J Obstet Gynecol, V214, P672, DOI 10.1016/j.ajog.2015.12.022
- Olive DL, 2008, NEW ENGL J MED, V359, P1136, DOI 10.1056/NEJMct0803719
- Parazzini F, 2017, EUR J OBSTET GYN R B, V209, P3, DOI 10.1016/j.ejogrb.2016.04.021
- Petta CA, 2005, HUM REPROD, V20, P1993, DOI 10.1093/humrep/deh869
- PRACTICE C, 2014, FERTIL STERIL, V101, P927, DOI 10.1016/J.FERTNSTERT.2014.02.012)
- Prentice A, 2000, COCHRANE DB SYST REV
- Reis FM, 2013, HUM REPROD UPDATE, V19, P406, DOI 10.1093/humupd/dmt010
- Sagsveen M., 2003, COCHRANE DB SYST REV, V4, DOI 10.1002/14651858.CD001297
- Simoens S, 2012, HUM REPROD, V27, P1292, DOI 10.1093/humrep/des073
- Soliman AM, 2016, HUM REPROD, V31, P712, DOI 10.1093/humrep/dev335
- Stratton P, 2011, HUM REPROD UPDATE, V17, P327, DOI 10.1093/humupd/dmq050
- Surrey ES, 2002, OBSTET GYNECOL, V99, P709, DOI 10.1016/S0029-7844(02)01945-2
- Vercellini P, 2011, REPROD SCI, V18, P114, DOI 10.1177/1933719110382921
- Watts NB, 2013, J CLIN DENSITOM, V16, P472, DOI 10.1016/j.jocd.2013.08.001