Elagolix reduces fatigue in women with endometriosis
Use of elagolix in the treatment of women with moderate-to-severe endometriosis-related pain yields a significant reduction in fatigue levels, according to the results of a phase III study.
“Fatigue is a well-recognized symptom of endometriosis that is associated with insomnia, depression, pain and occupational stress. In women with endometriosis, fatigue can lead to serious physical, psychologic and health-related quality of life issues,” the investigators said.
In the present study, 860 women aged 18–49 years who had a surgical diagnosis of endometriosis in the previous 10 years and moderate-to-severe endometriosis-associated pain were randomized to receive elagolix at either 150 mg daily (QD; n=246) or 200 mg twice daily (BID; n=243) or placebo (n=371) for 6 months. [Fertil Steril 2019;doi:10.1016/j.fertnstert.2019.02.031]
Every participant completed the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 6a questionnaire. PROMIS is composed of six questions to evaluate the severity of fatigue during the previous 7 days, at baseline and at various time points during treatment. Scores were converted to T-scores, with higher scores indicating greater fatigue.
At baseline, 54–74 percent of the population responded “quite a bit” or “very much” to questions that dealt with how fatigued they were, how bothersome their fatigue was and how run-down they felt. Median T-scores ranged 62.4–65.0, which is more than 1-standard deviation higher than the population average, reflecting the significant fatigue experienced by the endometriosis population, the investigators noted.
After 6 months of treatment, fatigue extent dropped to 29–43 percent in the elagolix 150 mg QD group, 14–29 percent in the 200 mg BID group and 35–50 percent in the placebo group. Fatigue T-scores decreased significantly with both elagolix dosing schedules vs placebo (mean differences, −2.21 with 150 mg QD and −5.90 with 200 mg BID; p=0.008 and p<0.001, respectively).
Of note, fatigue reduction was strongly associated with clinical response in endometriosis pain symptoms. Fatigues T-scores at month 6 decreased by 7.31 points in women who showed improvements in dysmenorrhea, by 6.62 points in those with improved nonmenstrual pelvic pain and by 4.31 points in those with improved dyspareunia relative to those who did not achieve response in pain symptoms (p<0.001 for all).
The results above suggest that treatments addressing pain symptoms can be expected to significantly ameliorate fatigue scores, according to the investigators.
Taken together, the present data “expand the benefits of treating women with endometriosis with the use of elagolix. [This drug], in addition to significantly reducing dysmenorrhea and nonmenstrual pain, provides significant lessening of fatigue, a relevant symptom of this disease,” they said.
“Currently, the first-line therapy recommended to treat endometriosis is the use of nonsteroidal anti-inflammatory drugs or other analgesics and combined oral contraceptive pills and progestins. Recommended second-line therapies include GnRH agonists, such as leuprolide acetate, with add-back hormone replacement therapy,” they added.