Appeal type: Medical necessity
Decision: Upheld

Diagnosis: Endometriosis.
Treatment: Orilissa 200mg OR TABS.
The insurer denied the Orilissa 200mg OR TABS.
The denial is upheld. 

The patient is a female. She underwent a laparoscopic excision of endometriosis, right salpingectomy and apparently a right ovarian cystectomy for an endometrioma. A non-communicating right uterine horn associated with a left unicornuate uterus was discovered. The patient was noted to have multiple small endometrial implants scattered over the peritoneum, including small sigmoid colon implants. Her gynecologist has recommended a referral to an advanced pelvic surgeon for removal of the horn. Orilissa has also been recommended for medical treatment of the endometriosis. The health plan has denied coverage of the Orilissa due to lack of medical necessity.

No, the treatment with Orilissa is not medically necessary.

The medical records and medical literature were thoroughly reviewed. Endometriosis is a chronic, estrogen-dependent, inflammatory condition that is characterized by the implantation of endometrial-like tissue outside the uterus and affects 6 to 10% (percent) of women of reproductive age. Endometriosis symptoms include dysmenorrhea, non-menstrual pelvic pain, and dyspareunia, as well as the less common symptoms of pain at ovulation, constipation, and painful urination. Endometriosis-associated pain can decrease the patient's quality of life and result in substantial economic burden. Dyspareunia can have profound interpersonal and psychological consequences. Endometriosis has multifactorial causes, including retrograde menstruation, genetic and environmental factors, alteration of the immune system, and ectopic differentiation of mesenchymal stem cells.

Estrogen plays a necessary role in the pathophysiology of endometriosis, since it promotes the implantation of endometrial tissue in the peritoneum, has proliferative and anti-apoptotic effects in endometrial cells, and stimulates local and systemic inflammation. On the basis of the "estrogen threshold hypothesis," complete estrogen suppression may not be needed to control endometriosis-associated pain, and estrogen may be adjusted to a level that is adequate to control pain but minimizes hypoestrogenic effects.

First-line therapies for endometriosis-related pain include nonsteroidal anti-inflammatory drugs (NSAIDs) and progestin-containing oral contraceptives. Second-line therapies involve injectable depot formulations of gonadotropin-releasing hormone (GnRH) agonists, such as leuprolide acetate. Although the injectable agents are effective and reduce estrogen levels to postmenopausal levels, they are associated with side effects (for example, progressive bone loss and severe vasomotor symptoms), which limit their use to six months without hormone-replacement therapy.

Medical options remain limited. Progestins are associated with bleeding, weight gain, and mood changes, and endometriosis is often associated with progesterone resistance. Androgenic agents such as danazol are associated with acne, hirsutism, and changes in lipid profiles. Surgical ablation or excision of lesions can be effective; however, symptoms often recur within 12 months, and more radical surgery (hysterectomy or oophorectomy) is a last resort. Pain management usually requires repeated courses of medical therapies or multiple surgical treatments until menopause. Elagolix is an oral, nonpeptide GnRH (gonadotropin-releasing hormone) antagonist. A phase 1 study showed that elagolix (at a dose of 200 milligram(mg) twice daily) led to nearly full estrogen suppression. Proof-of-concept phase 2 studies of elagolix showed efficacy in controlling both dysmenorrhea and non-menstrual pelvic pain, with an acceptable safety profile at a dose (once-daily 150 mg) that produces partial estrogen suppression. Two similar multicenter, double-blind, randomized, placebo-controlled, phase 3 trials (Elaris Endometriosis I and II [EM-I and EM-II]) of 6-month treatment with elagolix at two doses in women with moderate or severe endometriosis-associated pain have been published in peer review. Both higher and lower doses of elagolix were effective in improving dysmenorrhea and non-menstrual pelvic pain during a 6-month period in women with endometriosis-associated pain. Elagolix is approved by the FDA (United States Food and Drug Administration) for the management of moderate to severe pain associated with endometriosis.

The FDA-published prescribing label for Orilissa notes the following: "8.4 Pediatric Use - Safety and effectiveness of ORILISSA in patients less than 18 years of age have not been established. "

The safety and effectiveness of elagolix (Orilissa) in patients under the age of 18 has not been established and does not have FDA approval. Therefore, the use of Orilissa in this patient is not within the standard of care and it is not medically necessary.