Can a drug FDA approved for endometriosis become a mainstay for nonsurgical treatment of HMB in women with fibroids?
Elagolix is a GnRH antagonist that is approved in a 2-dose schedule for treatment of endometriosis. It is given orally and, as expected and clearly shown by the investigators in two identical, double-blind, randomized, placebo-controlled phase 3 trials, significantly reduces heavy menstrual bleeding (HMB) in women with fibroids. Because previous studies showed an increase in vasomotor symptoms and some negative impact on bone metabolism with elagolix, these studies, in addition to a placebo arm, included one arm with elagolix alone and one arm with “add-back therapy” that utilized estradiol and norethindrone acetate. The add-back therapy attenuated the hypoestrogenic effects of elagolix.
Results. In the first study group, 84% of those receiving elagolix alone achieved the primary end point, while the group that received elagolix plus add-back therapy had 69% success.
In the second study, both the elagolix group and the add-back group showed that 77% of patients met the primary end point criteria.
The incidences of hot flashes in the elagolix-alone groups were 64% and 43%, respectively, while with add-back therapy, they were 20% in both trials. In the placebo groups, 9% and 4% of participants reported hot flashes. At 6 months, the elagolix-only groups in both trials lost more BMD than the placebo groups, while BMD loss in both add-back groups was not statistically significant from the placebo groups.
Study strengths
Schlaff and colleagues conducted a very well-designed study. The two phase 3 clinical trials in preparation for drug approval were thorough and well reported. The authors are to be commended for including nearly 70% black women as study participants, since this is a racial group known to be affected by HMB resulting from fibroids.
Another strength was the addition of add-back therapy to the doses of elagolix. Concerns about bone loss from a health perspective and vasomotor symptoms from a quality-of-life perspective are not insignificant with elagolix-alone treatment, and proof that add-back therapy significantly diminishes or attenuates the efficacy of this entity is extremely important.
Elagolix is currently available (albeit not in the dosing regimen used in the current study or with built-in add-back therapy), and these study results offer an encouraging nonsurgical approach to HMB. The addition of add-back therapy to this oral GnRH antagonist will allow greater patient acceptance from a quality-of-life point of view because of diminution of vasomotor symptoms while maintaining BMD.
STEVEN R. GOLDSTEIN, MD
