Relugolix combo treatment may reduce opioid use in endometriosis-related discomfort

USA: Relugolix combo treatment taken once a day reduced endometriosis-related discomfort and was well tolerated by patients, says an article published in The Lancet.

Endometriosis is a prevalent cause of pelvic discomfort in women, and existing treatments are inadequate. Relugolix, an oral gonadotropin-releasing hormone receptor antagonist, in combination with estradiol and progestin was given to treat endometriosis-related pain. Linda C. Giudice and colleagues present the effectiveness and safety of a 24-week, once-daily oral relugolix combo treatment in women suffering from endometriosis-related discomfort.

Researchers randomly assigned women aged 18-50 years with surgically or directly visualized endometriosis with or without histological confirmation, or with histological diagnosis alone, to replicate placebo-controlled trials at community and hospital research centers across Africa, Europe, North America, Australasia, and South America. Participants were qualified if they had moderate to severe endometriosis-related pain and a dysmenorrhea Numerical Rating Scale (NRS) during the 35-day run-in period.

For 24 weeks, women were given a once-daily oral placebo, relugolix combination therapy, or delayed relugolix combination therapy (1:1:1). All patients, investigators, and sponsor personnel or representatives participating in the study's conduct were blinded to treatment assignment for the double-blind randomized treatment and follow-up period. Responder rates for dysmenorrhea and non-menstrual pelvic pain, both assessed on NRS ratings and analgesic usage, were the co-primary outcomes at week 24. The modified intent-to-treat population was used to assess efficacy and safety.

The key findings of this study were as follows:

1. In SPIRIT 1, 158 (75%) of 212 participants in the relugolix combination treatment group satisfied the dysmenorrhea responder criteria, while 57 (27%) of 212 participants in the placebo group did not.

2. In SPIRIT 2, 155 (75%) of 206 participants in the relugolix combined therapy group responded to dysmenorrhea treatment, compared to 62 (30%) of 204 participants in the placebo group.

3. In SPIRIT 1, 124 (58%) of the 212 patients in the relugolix combination treatment group satisfied the non-menstrual pelvic pain responder criteria, compared to 84 (40%) of the placebo group.

4. In SPIRIT 2, 136 (66%) of 206 participants in the relugolix combination treatment group responded to non-menstrual pelvic discomfort, compared to 87 (43%) of 204 participants in the placebo group.

5. Nasopharyngitis, Headache, and hot flushes were the most prevalent side effects.

6. There were no recorded deaths. The least-squares mean percentage decrease in lumbar spine bone mineral density in the relugolix combination therapy vs placebo groups was -0.70% versus 0.21% in SPIRIT 1 and -0.78% compared to 0.02% in SPIRIT 2, and it was -2.0% in SPIRIT 1 and -1.9% in SPIRIT 2.

In conclusion, "This oral medicine has the potential to meet an unmet clinical need for long-term medical treatment of endometriosis, thereby minimizing the requirement for opioids or recurrent surgical treatment," said the Authors.

Reference:

Giudice, L. C., As-Sanie, S., Arjona Ferreira, J. C., Becker, C. M., Abrao, M. S., Lessey, B. A., Brown, E., Dynowski, K., Wilk, K., Li, Y., Mathur, V., Warsi, Q. A., Wagman, R. B., & Johnson, N. P. (2022). Once daily oral relugolix combination therapy versus placebo in patients with endometriosis-associated pain: two replicate phase 3, randomised, double-blind, studies (SPIRIT 1 and 2). In The Lancet (Vol. 399, Issue 10343, pp. 2267–2279). Elsevier BV. https://doi.org/10.1016/s0140-6736(22)00622-5