Endometriosis is an estrogen-dependent disease1 that affects an estimated one in 10 women of reproductive age.2 In an international multicenter survey of 931 patients treated at 12 tertiary care centers in 10 countries, it was reported that 7 out of 10 endometriosis patients experience unresolved pain despite management.3
The most common symptoms associated with endometriosis include dysmenorrhea, non-menstrual pelvic pain and dyspareunia.2 Endometriosis symptoms can be debilitating and can impact day-to-day activities of women’s lives. In a regional United States survey of 107 patients with endometriosis, 85% of respondents reported reduced quality of their work and more than half reported their home life being affected because of their symptoms.4
While there is no cure for endometriosis, both medical and surgical treatments for pain related to endometriosis can be effective in managing endometriosis pain.5,6
Medical Management of Endometriosis Pain
Professional society guidelines, such as those from the American Society of Reproductive Medicine, recommend maximizing medical management to avoid multiple surgeries.5 They also recommend the use of a variety of medical options as initial treatment for women with endometriosis-related pain.5
After initial diagnosis and assessment, the first line of treatment for endometriosis-related pain typically includes oral contraceptives.7 Combination oral contraceptives include a synthetic progestin and estrogen. While the progestin component helps prevent a rise in estradiol, the synthetic estrogen may lead to continued endometriosis growth.8 Oral contraceptives are not specifically indicated to treat endometriosis pain9 and symptoms may return after stopping treatment.10
Other medical options can include over-the counter or prescription pain medications (such as nonsteroidal anti-inflammatory drugs).11
Gonadotropin-releasing hormone (GnRH) antagonists are another potential option to treat endometriosis-related pain. They work by competing with endogenous GnRH for GnRH receptor occupancy and blocking receptors upon binding.12,13 When a GnRH antagonist enters the pituitary, it acts like a player in a game of musical chairs, competing with GnRH to sit in the receptor. Like a molecular game of musical chairs, GnRH is left with fewer receptors to activate.12,13 GnRH receptor antagonism leads to dose-dependent suppression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH).12-16 Suppression of these two hormones leads to decreased blood concentrations of ovarian sex hormones estradiol and progesterone.12
Progestins and GnRH agonists may also be considered to treat endometriosis pain. They help by slowing the growth of the endometrial tissue and keep new lesions from forming, but will not make existing growths go away.2
Surgical Management of Endometriosis Pain
Surgical interventions may also be considered for some women with endometriosis pain. While surgical treatment can be effective, many women require additional medical or surgical retreatment within two years after laparoscopic surgery.2 Definitive surgical management, such as a hysterectomy, may be considered in women who are not concerned about preserving fertility and where medical management and more conservative surgical options have not provided adequate symptom relief.6
ORILISSA® (elagolix) for Moderate to Severe Pain Associated with Endometriosis
ORILISSA, a GnRH receptor antagonist, is the first FDA-approved oral treatment for moderate to severe endometriosis pain in over a decade.12 ORILISSA is contraindicated in women who are pregnant, women with known osteoporosis, women with severe hepatic impairment, or in women taking strong organic anion transport polypeptide (OATP) 1B1 inhibitors such as cyclosporine and gemfibrozil.12
With ORILISSA, suppression of LH and FSH begins between four to six hours after administration of a single dose and is readily reversible* upon discontinuation.12,16 ORILISSA partially lowers the level of ovarian sex hormones estradiol and progesterone, and after 24 hours, subsequent suppression of estradiol levels occurs.12,14,16
*Does not imply onset of efficacy during this time.
ORILISSA’s approval was supported by data from two prospective randomized controlled robust replicate studies in the largest endometriosis Phase 3 study program conducted to date (N=1686). Select enrollment criteria and baseline patient characteristics: Premenopausal women aged 18-49 years with moderate to severe dysmenorrhea and non-menstrual pelvic pain who were surgically diagnosed with endometriosis in the previous 10 years.12
Response was defined as clinically meaningful reduction in dysmenorrhea and non-menstrual pelvic pain with no increase in rescue analgesic use (nonsteroidal anti-inflammatory drugs or opioids). Women were defined as responders if they experienced a clinically meaningful reduction in dysmenorrhea and non-menstrual pelvic pain beyond a predetermined threshold and no increase in analgesic use (nonsteroidal anti-inflammatory drug or opioid) for endometriosis-associated pain.
Clinically meaningful reduction in pain was defined as a calculated threshold of improvement in pain score in each study. The threshold was determined based on an analysis of the change in pain score that corresponded to “much improved” or “very much improved” on the Patient Global Impression of Change questionnaire.
Study results demonstrated clinically meaningful response rates with ORILISSA 150 mg once-daily (QD) vs. placebo for dysmenorrhea and non-menstrual pelvic pain.13,18 Mean change in dyspareunia scores were not statistically significant with ORILISSA 150 mg QD.17 Clinically meaningful response rates were also demonstrated with ORILISSA 200 mg twice-daily (BID) vs. placebo for dysmenorrhea, non-menstrual pelvic pain and dyspareunia.12,17,18
ORILISSA is available in two oral dosages (150 mg once daily or 200 mg twice daily) which allows physicians to individualize treatment based on a woman’s specific type and severity of endometriosis pain.11 The lowest effective dose of ORILISSA should be used based on severity of symptoms and treatment objectives.12
Individualizing Endometriosis Pain Treatment
Treatment for endometriosis pain must be individualized and both medical and surgical treatments can be effective.6 Determining the best treatment approach requires a comprehensive understanding of a woman’s medical history, symptoms and treatment goals. Current nonsurgical treatment options for endometriosis are limited9 and continued research for additional non-invasive treatment options is needed to reduce the personal burdens of endometriosis and ultimately help to improve the lives of women impacted by this chronic and painful disease.2,19,20,21
For more information, visit ORILISSA.com.
ORILISSA® (elagolix) is indicated for the management of moderate to severe pain associated with endometriosis.
IMPORTANT SAFETY INFORMATION
• ORILISSA is contraindicated in women who are pregnant (exposure to ORILISSA early in pregnancy may increase the risk of early pregnancy loss), in women with known osteoporosis or severe hepatic impairment (due to risk of bone loss), or with concomitant use of strong organic anion transporting polypeptide (OATP) 1B1 inhibitors (e.g., cyclosporine and gemfibrozil).
WARNINGS AND PRECAUTIONS
• ORILISSA causes a dose-dependent decrease in bone mineral density (BMD), which is greater with increasing duration of use and may not be completely reversible after stopping treatment.
• The impact of ORILISSA-associated decreases in BMD on long-term bone health and future fracture risk is unknown. Consider assessment of BMD in patients with a history of low-trauma fracture or other risk factors for osteoporosis or bone loss, and do not use in women with known osteoporosis.
• Limit the duration of use to reduce the extent of bone loss.
Change in Menstrual Bleeding Pattern and Reduced Ability to Recognize Pregnancy
• Women who take ORILISSA may experience a reduction in the amount, intensity, or duration of menstrual bleeding, which may reduce the ability to recognize the occurrence of pregnancy in a timely manner. Perform pregnancy testing if pregnancy is suspected, and discontinue ORILISSA if pregnancy is confirmed.
Suicidal Ideation, Suicidal Behavior, and Exacerbation of Mood Disorders
• Suicidal ideation and behavior, including one completed suicide, occurred in subjects treated with ORILISSA in the endometriosis clinical trials.
• ORILISSA users had a higher incidence of depression and mood changes compared to placebo and ORILISSA users with a history of suicidality or depression had an increased incidence of depression. Promptly evaluate patients with depressive symptoms to determine whether the risks of continued therapy outweigh the benefits. Patients with new or worsening depression, anxiety, or other mood changes should be referred to a mental health professional, as appropriate.
• Advise patients to seek immediate medical attention for suicidal ideation and behavior. Reevaluate the benefits and risks of continuing ORILISSA if such events occur.
Hepatic Transaminase Elevations
• In clinical trials, dose-dependent elevations of serum alanine aminotransferase (ALT) at least 3 times the upper limit of the reference range occurred with ORILISSA.
• Use the lowest effective dose and instruct patients to promptly seek medical attention in case of symptoms or signs that may reflect liver injury, such as jaundice.
• Promptly evaluate patients with elevations in liver tests to determine whether the benefits of continued therapy outweigh the risks.
Reduced Efficacy with Estrogen-Containing Contraceptives
• Based on the mechanism of action of ORILISSA, estrogen-containing contraceptives are expected to reduce the efficacy of ORILISSA. The effect of progestin-only contraceptives on the efficacy of ORILISSA is unknown.
• Advise women to use non-hormonal contraceptives during treatment and for one week after discontinuing ORILISSA.
• The most common adverse reactions (>5%) in clinical trials included hot flushes and night sweats, headache, nausea, insomnia, amenorrhea, anxiety, arthralgia, depression-related adverse reactions, and mood changes.
These are not all the possible side effects of ORILISSA.
Safety and effectiveness of ORILISSA in patients less than 18 years of age have not been established.
Please click here for Full Prescribing Information and Medication Guide.
- Serdar B, et al. Role of Estrogen Receptor-β in Endometriosis. Semin Reprod Med. 2012;30(1):39-45.
- The American College of Obstetricians and Gynecologists (2018). Frequently Asked Questions: Endometriosis. https://www.acog.org/Patients/FAQs/Endometriosis.
- De Graaff AA, D’Hooghe TM, Dunselman GAJ, Dirksen CD, Hummelshoj L, WERF EndoCost Consortium, Simoens S. The significant effect of endometriosis on physical, mental and social wellbeing: results from an international cross-sectional survey. Hum Reprod. 2013;28(10):2677-2685.
- Fourquet J, et al. Patients’ Report on How Endometriosis Affects Health, Work, and Daily Life. Fertil Steril. 2010 May 1; 93(7): 2424–2428.
- The Practice Committee of the American Society for Reproductive Medicine. Treatment Of Pelvic Pain Associated With Endometriosis: A Committee Opinion. Fertil Steril. 2014 Apr;101(4):927-35.
- Armstrong C. ACOG Updates Guideline on Diagnosis and Treatment of Endometriosis. Am Fam Physician. 2011 Jan 1;83(1):84-85.
- American College of Obstetricians and Gynecologists. Practice bulletin no. 114: management of endometriosis. Obstet Gynecol. 2010;116(1):223-236.
- Kodaman PH. Current strategies for endometriosis management. Obstet Gynecol Clin North Am. 2015;42(1):87-101.
- AM, et al. On-Label And Off-Label Drug Use In The Treatment Of Endometriosis. Fertil Steril. 2015 Mar;103(3):612-25.
- Mayo Clinic (2018). Endometriosis. https://www.mayoclinic.org/diseases-conditions/endometriosis/diagnosis-treatment/drc-20354661
- Quaas AM, et al. On-Label And Off-Label Drug Use In The Treatment Of Endometriosis. Fertil Steril. 2015 Mar;103(3):612-25.
- ORILISSA [package insert]. North Chicago, IL: AbbVie Inc.
- Huirne JA, Lambalk CB. Gonadotropin-releasing-hormone-receptor antagonists. The Lancet. 2001;358(9295):1793-1803.
- Struthers RS, Nicholls AJ, Grundy J, et al. Suppression of Gonadotropins and Estradiol in Premenopausal Women by Oral Administration of the Nonpeptide Gonadotropin-Releasing Hormone Antagonist Elagolix. J Clin Endocrinol Metab. 2009;94(2):545-551.
- Ezzati M, Carr BR. Elagolix, a novel, orally bioavailable GnRH antagonist under investigation for the treatment of endometriosis-related pain. Womens Health (Lond). 2015;11(1):19-28.
- Ng J, Chwalisz K, Carter DC, Klein CE. Dose-Dependent Suppression of Gonadotropins and Ovarian Hormones by Elagolix in Healthy Premenopausal Women. J Clin Endocrinol Metab. 2017;102(5):1683-1691.
- Taylor HS, Giudice LC, Lessey BA, et al. Treatment of endometriosis-associated pain with elagolix, an oral GnRH antagonist. N Engl J Med. 2017;377(1):28-40.
- Data on file ABVRRTI66651
- Soliman AM, et al. Incremental Direct and Indirect Cost Burden Attributed to Endometriosis Surgeries in the United States. Fertil Steril. 2017 May;107(5):1181-1190.e2.
- Fourquet J, et al. Quantification of the Impact of Endometriosis Symptoms on Health-Related Quality of Life and Work Productivity. Fertil Steril. 2011 Jul;96(1):107-12.
- Fuldeore MJ, et al. Prevalence and Symptomatic Burden of Diagnosed Endometriosis in the United States: National Estimates from a Cross-Sectional Survey of 59,411 Women. Gynecol Obstet Invest. 2017;82(5):453-461.
AbbVie Inc. North Chicago, IL 60064 US-ORIL-190202 April 2019