Achieving clinically meaningful response in endometriosis pain symptoms is associated with improvements in health-related quality of life and work productivity: analysis of 2 phase III clinical trials

Pokrzywinski, Robin; Soliman, Ahmed M.; Chen, Jun; Snabes, Michael C.; Coyne, Karin S.; Surrey, Eric S.; Taylor, Hugh S.

doi:10.1016/j.ajog.2019.11.1255

Cited by 30 publications

(32 citation statements)

References 18 publications

(37 reference statements)

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“…Although there are dissenting views, 28 recent studies support the use of this new, orally active modality. [29][30][31][32][33] The aim of this review is to provide a practical guide for use of elagolix based on available evidence and clinical experience. It is anticipated that with ongoing experience, expertise will continue to develop regarding the best use of pharmaceutical agents for the management of endometriosis symptomatology.…”

Section: Introductionmentioning

confidence: 99%

A Clinician's Guide to the Treatment of Endometriosis with Elagolix

Leyland

Estes

Lessey³

et al. 2021

Journal of Women's Health

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Pain associated with endometriosis is a considerable burden for women, permeating all aspects of their lives, from their ability to perform daily activities to their quality of life. Although there are many options for endometriosis-associated pain management, they are often limited by insufficient efficacy, inconvenient routes of administration, and/or intolerable side effects. Elagolix, a nonpeptide, small-molecule gonadotropinreleasing hormone (GnRH) receptor antagonist, is the first new oral therapy to be approved for the treatment of endometriosis-associated pain in the United States in more than a decade. Modulation of estradiol with elagolix is dose dependent and ranges from partial to full suppression. Clinical evidence has shown that elagolix at both approved doses (150 mg once daily and 200 mg twice daily) is effective for reducing symptoms of pelvic pain (dysmenorrhea, nonmenstrual pelvic pain, and dyspareunia), improving quality of life, and decreasing use of rescue analgesics (nonsteroidal anti-inflammatory drugs and/or opioids). The availability of two dosing options allows for individualization of treatment based on baseline clinical factors and response to therapy. Elagolix is well tolerated, with less pronounced hypoestrogenic effects compared with GnRH agonists. This review provides an overview of elagolix, highlighting currently available treatment options and the application of this new treatment for women with endometriosis-associated pain.

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Section: Introductionmentioning

confidence: 99%

A Clinician's Guide to the Treatment of Endometriosis with Elagolix

Leyland

Estes

Lessey³

et al. 2021

Journal of Women's Health

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“…This may indicate that pelvic pain is more strongly associated with peritoneal macrophage dysfunction than the presence of active endometriosis lesions per se. Current treatment approaches for endometriosis focus on either surgical removal of disease or hormonal suppression of lesion growth but this does not improve pain symptoms in all women (22,33,34). Our new data suggest that divergence in pain responses may be influenced by the direct response of peritoneal macrophages to a given treatment.…”

Section: Discussionmentioning

confidence: 85%

“…For example, GnRH agonists are reported to reduce pelvic pain in women with endometriosis (35) and, notably, this treatment has been shown to increase PMφ cytotoxicity (36) and reduce peritoneal fluid concentrations of the pain-correlated cytokine IL6 in women with endometriosis (37). Large-scale clinical trials have shown that the non-peptide GnRH antagonist Elagolix has a clinically meaningful reduction in the pain domain of EHP30 but only in around half of the women tested (22,34). To the best of our knowledge, the impact of Elagolix on peritoneal macrophage function has not been investigated but baseline differences in peritoneal macrophage phenotype could account for some of the reported differences in pain response.…”

Section: Discussionmentioning

confidence: 99%

Peritoneal macrophage phenotype correlates with pain scores in women with suspected endometriosis

Gibson

Collins

Leo

et al. 2020

Preprint

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Objective: To characterise peritoneal macrophage populations in women with suspected endometriosis and assess if they are correlated with severity of pelvic pain symptoms. Design: Flow cytometry analysis of peritoneal fluid samples and clinical data. Setting: University Research Institute. Patients: Clinical questionnaires, surgical data and peritoneal fluid were collected with informed consent from women undergoing diagnostic laparoscopy for suspected endometriosis (n=54). Intervention(s): None Main Outcome Measure(s): Severity of pelvic pain symptoms was assessed by the EHP-30 questionnaire. Immune cells recovered from peritoneal fluid were analysed by flow cytometry. Results: Pain scores (pain domain of EHP30) did not differ according to endometriosis diagnosis, stage of endometriosis or whether or not women were receiving hormone treatment. Analysis of immune cells in peritoneal fluid revealed two populations of peritoneal macrophages: CD14high and CD14low which were not altered by menstrual cycle phase or hormone treatment. CD14high peritoneal macrophages were increased in women with endometriosis compared to those without but were not altered by coincident reproductive health issues such as infertility or heavy menstrual bleeding. Peritoneal macrophage phenotype correlated with pelvic pain symptoms in women with suspected endometriosis. Notably, CD14high peritoneal macrophages negatively correlated with pain scores whereas CD14low peritoneal macrophages were positively correlated. This association was independent of endometriosis diagnosis. Conclusion: Peritoneal macrophage phenotypes correlate with pelvic pain symptoms in women with suspected endometriosis and are altered by presence of disease. These results provide new insight into the association between endometriosis pathophysiology and pelvic pain symptoms.

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“…Dyspareunia, dysmenorrhea, and non-menstrual pelvic pain symptom severity were determined, and pain severity was recorded by patients throughout the study using an Endometriosis Daily Pain Impact eDiary, which consists of pain impact items and uses a scoring system that have both been validated, as previously described. 12,15,16 For dyspareunia, women were asked to choose the item that best described their pain during sexual intercourse during the last 24 hours. Options given for women to rank their dyspareunia were none (score 0, no discomfort during sexual intercourse), mild (score 1, I was able to tolerate the discomfort during sexual intercourse), moderate (score 2, intercourse was interrupted because of pain), severe (score 3, I avoided sexual intercourse because of pain), or not applicable (I was not sexually active for reasons other than my endometriosis or did not have sexual intercourse).…”

Section: Discussionmentioning

confidence: 99%

“…Moderate to severe endometriosisassociated pain was based on the mean pain scores during the month before baseline in the self-reported Endometriosis Daily Pain Impact eDiary with endometriosis-associated pain diagnosed by the investigator, as described previously. 12,15,16 Women were randomized 3:2:2 to receive placebo, elagolix 150 mg once daily (150-mg cohort), or elagolix 200 mg twice daily (200-mg cohort), for 6 months with a 12-month follow-up period. The coprimary endpoints for both studies were the proportion of women who achieved a clinical response for dysmenorrhea and non-menstrual pelvic pain at month 3 of treatment.…”

Section: Methodsmentioning

confidence: 99%

Clinically Meaningful Reduction in Dyspareunia Is Associated with Significant Improvements in Health-Related Quality of Life Among Women with Moderate to Severe Pain Associated with Endometriosis: A Pooled Analysis of Two Phase III Trials of Elagolix

Agarwal

Soliman

Pokrzywinski

et al. 2020

The Journal of Sexual Medicine

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Background: Dyspareunia experienced by women diagnosed with endometriosis is associated with a decreased health-related quality of life (HRQoL). Aim: We evaluated the relationship of clinically meaningful improvements in dyspareunia with HRQoL changes among women with endometriosis. Methods: This was a post hoc analysis of pooled data from the phase III ELARIS-I and ELARIS-II clinical trials. Women aged 18e49 years with moderate to severe endometriosis-associated pain were randomized to placebo, elagolix 150 mg once daily, or elagolix 200 mg twice daily. HRQoL was measured using the validated Endometriosis Health Profile-30 questionnaire (EHP-30), consisting of 5 core domains and a sexual intercourse modular domain. Dyspareunia was ranked 0e3 (none, mild, moderate, or severe) or not applicable using a daily eDiary and averaged monthly. A woman with a clinically meaningful dyspareunia response (dyspareunia responder) was defined as a woman with a reduction from the baseline in dyspareunia score greater than or equal to a predetermined cutoff while maintaining stable/decreased analgesic use. Outcomes: Dyspareunia response impact on EHP-30 scores was determined at 3 and 6 months using multivariate linear regression controlling for age, baseline EHP-30 scores, and dysmenorrhea and non-menstrual pelvic pain symptom severity. Results: Analysis included 1,368 women with a mean age of 32.2 years. Dyspareunia responders had significant improvements vs non-responders in all adjusted mean EHP-30 domain scores at months 3 and 6 (control and powerlessness: À17.8 and À18.5; emotional well-being: À10.0 and À10.4; pain: À15.3 and À15.7; selfimage: À11.4 and À12.8; social support: À14.3 and À14.0; and sexual intercourse: À18.1 and À19.7; all P < .0001). Clinical Implications: Dyspareunia improvements are associated with both personal and psychological benefits. Strengths & Limitations: This study involved a large sample of women from a well-defined patient population to provide statistical power in evaluating the results. As such, the findings may not be generalizable in a real-world setting. Although the perception of dyspareunia and its severity and the associated effect on HRQoL was subjective, the use of a large patient sample was used to minimize potential issues with this limitation. Conclusion: Clinically meaningful responses in dyspareunia are associated with improvements across multiple HRQoL domains among women with endometriosis. Agarwal SK, Soliman AM, Pokrzywinski RM, et al.

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Achieving clinically meaningful response in endometriosis pain symptoms is associated with improvements in health-related quality of life and work productivity: analysis of 2 phase III clinical trials

Cited by 30 publications

References 18 publications

A Clinician's Guide to the Treatment of Endometriosis with Elagolix

A Clinician's Guide to the Treatment of Endometriosis with Elagolix

Peritoneal macrophage phenotype correlates with pain scores in women with suspected endometriosis

Clinically Meaningful Reduction in Dyspareunia Is Associated with Significant Improvements in Health-Related Quality of Life Among Women with Moderate to Severe Pain Associated with Endometriosis: A Pooled Analysis of Two Phase III Trials of Elagolix

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