Stepwise Approach to the Management of Endometriosis-Related Dysmenorrhea: A Cost-Effectiveness Analysis.

OBJECTIVE: To evaluate the cost effectiveness of sequential medical and surgical therapy for the treatment of endometriosis-related dysmenorrhea. METHODS: A cost-effectiveness model was created to compare three stepwise medical and surgical treatment strategies compared with immediate surgical management for dysmenorrhea using a health care payor perspective. A theoretical study cohort was derived from the estimated number of reproductive age (18-45) women in the United States with endometriosis-related dysmenorrhea. The treatment strategies modeled were: strategy 1) nonsteroidal antiinflammatory drugs (NSAIDs) followed by surgery; strategy 2) NSAIDs, then short-acting reversible contraceptives or long-acting reversible contraceptives (LARCs) followed by surgery; strategy 3) NSAIDs, then a short-acting reversible contraceptive or LARC, then a LARC or gonadotropin-releasing hormone modulator followed by surgery; strategy 4) proceeding directly to surgery. Probabilities, utilities, and costs were derived from the literature. Outcomes included cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios. Univariate, bivariate, and multivariate sensitivity analyses were performed. RESULTS: In this theoretical cohort of 4,817,894 women with endometriosis-related dysmenorrhea, all medical and surgical treatment strategies were cost effective at a standard willingness-to-pay threshold of $100,000 per QALY gained when compared with surgery alone. Strategy 2 was associated with the lowest cost per QALY gained ($1,155). Requiring a trial of a third medication before surgery would cost an additional $257 million, compared with proceeding to surgery after failing two medical treatments. The probability of improvement with surgery would need to exceed 83% for this to be the preferred first-line approach. CONCLUSION: All sequential medical and surgical management strategies for endometriosis-related dysmenorrhea were cost effective when compared with surgery alone. A trial of hormonal management after NSAIDs, before proceeding to surgery, may provide cost savings. Delaying surgical management in an individual with pain refractory to more than three medications may decrease quality of life and increase cost.

The impact of high-risk and chronic opioid use among commercially insured endometriosis patients on health care resource utilization and costs in the United States.

OBJECTIVES: Evaluate all-cause and endometriosis-related health care resource utilization and costs among newly diagnosed endometriosis patients with high-risk versus low-risk opioid use or patients with chronic versus non-chronic opioid use. METHODS: A retrospective analysis of IBM MarketScan® Commercial Claims data from 2009 to 2018 was performed for females aged 18 to 49 with newly diagnosed endometriosis (International Classification of Diseases, Ninth Edition code: 617.xx; International Classification of Diseases, Tenth Edition code: N80.xx). Two sub-cohorts were identified: high-risk (⩾1 day with ⩾90 morphine milligram equivalents per day or ⩾1-day concomitant benzodiazepine use) or chronic opioid utilization (⩾90-day supply prescribed or ⩾10 opioid prescriptions). High-risk or chronic utilization was evaluated during the 12-month assessment period after the index date. Index date was the first opioid prescription within 12 months following endometriosis diagnosis. All outcomes were assessed over 12-month post-assessment period while adjusting for demographic and clinical characteristics. RESULTS: Out of 61,019 patients identified, 18,239 had high-risk opioid use and 5001 chronic opioid use. Health care resource utilization drivers were outpatient visits and pharmacy fills, which were higher among high-risk versus low-risk patients (outpatient visits: 17.49 vs 15.51; pharmacy fills: 19.58 vs 16.88, p < 0.0001). Chronic opioid users had a higher number of outpatient visits (19.53 vs 15.00, p < 0.0001) and pharmacy fills (23.18 vs 16.43, p < 0.0001) compared to non-chronic opioid users. High-risk opioid users had significantly higher all-cause health care costs compared to low-risk opioid users (US$16,377 vs US$13,153; p < 0.0001). Chronic opioid users also had significantly higher all-cause health care costs compared to non-chronic opioid users (US$20,930 vs US$12,272; p < 0.0001). Similar patterns were observed among endometriosis-related HCRU, except pharmacy fills among high-risk and chronic sub-cohorts. CONCLUSION: This analysis demonstrates significantly higher all-cause and endometriosis-related health care resource utilization and total costs for high-risk opioid users compared to low-risk opioid users among newly diagnosed endometriosis patients over 1 year. Similar trends were observed for comparing chronic opioid users with non-chronic opioid users, except for endometriosis-related pharmacy fills and associated costs.

Healthcare Resource Use and Costs Associated with Opioid Initiation Among Patients with Newly Diagnosed Endometriosis with Commercial Insurance in the USA.

INTRODUCTION: To compare all-cause and endometriosis-related healthcare resource utilization (HCRU) and healthcare costs by service categories (outpatient, inpatient, emergency room [ER], pharmacy) among patients with newly diagnosed endometriosis using opioids compared to patients with endometriosis not using opioids. METHODS: A retrospective analysis of IBM® MarketScan® Commercial Claims data from 2009 to 2018 was performed for women aged 18-49 with newly diagnosed endometriosis (International Classification of Diseases (ICD)-9 code 617.xx; ICD-10 code N80.xx) over 24 months follow-up. Patients were stratified on the basis of opioid use within 12 months post first endometriosis diagnosis date. Patients with opioid use were 1:1 matched to patients without opioid use using propensity score matching. RESULTS: A total of 85,329 female patients with a new endometriosis diagnosis were identified and 48,470 patients (24,235 opioid and 24,235 non-opioid users) remained after inclusion-exclusion criteria and matching. Opioid patients had an estimated mean 30.33 outpatient visits, 29.59 pharmacy fills, 0.28 inpatient visits, 0.65 ER visits, and total length of stay (LOS) was 1.01 days. Non-opioid patients had an estimated mean 27.94 outpatient visits, 22.06 pharmacy fills, 0.23 inpatient visits, 0.42 ER visits, and total LOS was 0.82 days. On average, opioid patients had significantly greater all-cause HCRU compared to non-opioid patients (all p < 0.0001). Among endometriosis-related healthcare utilization, there were similar ER visits, but lower outpatient visits, inpatient visits, and total LOS and higher pharmacy fills among opioid and non-opioid patients. Estimated mean all-cause costs were higher among opioid ($26,755) vs. non-opioid ($19,302) users (p < 0.0001). A similar trend was observed for estimated mean endometriosis-related costs. CONCLUSION: This analysis observed significantly higher all-cause HCRU and costs for opioid users compared to non-opioid users among patients with newly diagnosed endometriosis. While observed endometriosis-related costs were significantly higher in opioid users compared to non-opioid users during a 24-month follow-up period, endometriosis-related HCRU varied by service categories for these two populations over this time period.

Healthcare Consumption and Cost Estimates Concerning Swedish Women with Endometriosis.

INTRODUCTION: Endometriosis is known for its substantial effect on women's wellbeing and quality of life. In order to evaluate disease burden, treatments and health services, assessments of healthcare consumption and cost estimates are necessary. OBJECTIVES: The aim of this study was to estimate healthcare consumption and annual cost per woman with endometriosis in Sweden and to examine healthcare consumption and costs in different age groups. METHODS: A questionnaire was distributed to 400 members of the Endometriosis Association and to 400 randomly selected women with surgically confirmed endometriosis. Official statistics were obtained via correspondence, publications, and database searches. RESULTS: Analysis of the 431 returned questionnaires showed that women under 30 years utilized more inpatient and outpatient care than older women. The mean annual cost among all women was EUR 8,768/woman. The direct healthcare cost of managing the disease was EUR 4,282, while the indirect cost was EUR 4,486. Absence from work was reported by 32% of the women, while 36% reported reduced time at work because of endometriosis. CONCLUSION: Our results confirm the substantial negative effect of endometriosis upon women's lives and their relatively high healthcare consumption.

A Longitudinal Assessment of the Impact of Endometriosis on Patients' Salary Growth and Risk of Leaving the Workforce.

INTRODUCTION: This retrospective cohort study evaluated the impact of endometriosis on the risks of work loss events and salary/growth over a 5-year period. METHODS: Women aged 18-49 years with ≥ 1 endometriosis diagnosis were identified in a claims database and matched 1:1 to women without endometriosis (controls). The index date was the first endometriosis diagnosis date (endometriosis cohort) or a random date during the period of continuous eligibility (controls). Baseline characteristics were compared between cohorts descriptively. Average annual salaries were compared over the 5 years post-index using generalized estimating equations accounting for matching. Time-to-event analyses assessed risk of short-term disability, long-term disability, leave of absence, early retirement, and any event of leaving the workforce (Kaplan-Meier curves with log-rank tests). RESULTS: A total of 6851 matched pairs (mean age at index date: 38.7 years) were included in the salary growth analysis, with a subset of 1981 pairs in the risk of leaving the workforce analysis. In year 1, the endometriosis cohort had a lower average annual salary ($61,322) than controls ($64,720); salaries were lower in years 2-5 by $3697-$6600 (all p < 0.01). The endometriosis cohort experienced smaller salary growth than controls in all years, ranging from $438 vs. $1058 in year 1 to $4906 vs. $7074 in year 5 (all p < 0.05). In the Kaplan-Meier analyses, patients with endometriosis were significantly more likely than controls to leave the workforce for any reason, take a leave of absence, and use short-term disability (all log-rank tests p < 0.001). Additionally, the median number of years to each of these events was lower for the endometriosis cohort relative to the matched controls. Sensitivity analyses among patients with moderate-to-severe endometriosis and by salary brackets confirmed the primary analyses. CONCLUSIONS: Patients with endometriosis experienced lower annual salary and salary growth, as well as higher risks of work loss events, compared with matched controls.

Impact of Endometriosis Diagnostic Delays on Healthcare Resource Utilization and Costs.

INTRODUCTION: Endometriosis symptoms are nonspecific and overlap with other gynecologic and gastrointestinal diseases, leading to long diagnostic delays. The burden of endometriosis has been documented; however, little is known about the impact of diagnostic delays on healthcare costs leading up to diagnoses. The purpose of this study was to examine the economic impact of diagnostic delays on pre-diagnosis healthcare utilization and costs among patients with endometriosis. METHODS: This was a retrospective database study of adult patients with a diagnosis of endometriosis from 1 January 2004 to 31 July 2016. Patients had continuous health plan enrollment 60 months prior to and 12 months following the earliest endometriosis diagnosis and ≥ 1 pre-diagnosis endometriosis symptom (dyspareunia, generalized pelvic pain, abdominal pain, dysmenorrhea, or infertility). Patients were assigned to short (≤ 1 year), intermediate (1-3 years), or long (3-5 years) delay cohorts based on the length of their diagnostic delay (time from first symptom to diagnosis). Healthcare resource utilization and costs were calculated and compared by cohort in the 60-month pre-diagnosis period. RESULTS: A total of 11,793 patients were included in the study, of which 37.7% (4446/11,793), 27.0% (3179/11,793), and 35.3% (4168/11,793) had short, intermediate, and long delays, respectively. Patients with intermediate or long diagnostic delays had consistently more all-cause and endometriosis-related emergency visits and inpatient hospitalizations in the pre-diagnosis period than patients with short delays. Pre-diagnosis all-cause healthcare costs were significantly higher among patients with longer diagnostic delays, averaging $21,489, $30,030, and $34,460 among patients with a short, intermediate, and long delay, respectively (p < 0.001 for all pairwise comparisons). Endometriosis-related costs accounted for 12.5% ($3553/$28,376) of all-cause costs and followed a similar pattern. CONCLUSION: Patients with endometriosis who had longer diagnostic delays had more pre-diagnosis endometriosis-related symptoms and higher pre-diagnosis healthcare utilization and costs compared with patients who were diagnosed earlier after symptom onset, providing evidence in support of earlier diagnosis.

Hospital-Associated Cost of Endometriosis in Canada: A Population-Based Study.

STUDY OBJECTIVE: To describe the hospital-associated cost of endometriosis in Canada from April 2008 to March 2013. DESIGN: Population-based descriptive study. SETTING: Canada, with the exception of the province of Quebec. PATIENTS: All women aged 15 to 59 years discharged with endometriosis between April 2008 and March 2013. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Over 5 years, 47 021 women were admitted for endometriosis, resulting in a total hospital cost of Canadian dollars (CaD) $152.21 million (US dollars [US $] 147.79 million) and per-case cost of CaD $3237 (US $3143). Uterine endometriosis accounted for 28.29% of cases, ovarian endometriosis 27.44%, and other endometriosis 44.27%. Cost for uterine endometriosis was the highest at CaD $4137 (US $4017) per case, followed by ovarian endometriosis (CaD $3506; US $3404) and other endometriosis (CaD $2495; US $2422). The highest number of cases were in the groups aged 35 to 39 years (20.77%) and 40 to 44 years (20.44%). Hysterectomy accounted for 29.57% of surgical procedures. Encounters with hysterectomy were the costliest at CaD $5062 (US $4915) per case, followed by the ones with other surgical procedures at CaD $2477 (US $2405) per case, and admissions with no surgical procedure at CaD $2164 (US $2101) per case. CONCLUSION: The hospital cost associated with endometriosis was approximately CaD $30 million (US $29.56 million) per year, whereas uterine endometriosis, hysterectomy, and older age were found to have a higher average cost per case. Although this study focuses specifically on hospital admission and does not account for outpatient costs or indirect costs, it nonetheless highlights the economic burden of this debilitating disease on Canadian society during the study period.

Healthcare utilization and cost burden among women with endometriosis by opioid prescription status in the first year after diagnosis: a retrospective claims database analysis.

Aims: Opioids do not represent standard therapy for endometriosis; however, women with endometriosis are frequently prescribed an opioid to manage related abdominal or pelvic pain. The aim of this study was to evaluate the impact of opioid use on endometriosis-related economic and healthcare burden in the United States.Materials and methods: We performed a retrospective, propensity-matched cohort analysis of the Truven MarketScan Commercial database from 1 January 2011 to 31 December 2016. Eligible women had at least 1 inpatient or 2 outpatient codes for endometriosis and 12 months of continuous enrollment before and after the index date (i.e. first recorded endometriosis diagnosis). The primary analysis examined healthcare costs and utilization for 12 months after the index date in women who filled at least 1 opioid prescription versus those who did not. The secondary analysis examined healthcare costs and utilization by the pattern of opioid use.Results: The primary analysis matched 43,516 women across 2 groups and the secondary analysis matched 13,230 women across 5 groups. In the primary analysis, total 12-month healthcare costs were significantly higher in the opioid group compared to the non-opioid group ($29,236.00 vs. $18,466.00, respectively; p < .001); the same pattern was observed for all healthcare utilization parameters. In the secondary analysis, higher morphine equivalent daily dose and proportion of days covered were associated with the highest healthcare costs and utilization compared to the non-opioid group.Limitations: Retrospective design and inability to confirm whether filled opioid prescriptions were actually taken.Conclusions: Filling an opioid prescription within 1 year after an endometriosis diagnosis was associated with significant excess healthcare burden. Patients prescribed an opioid may experience inadequate symptom management and benefit from the use of disease-specific, non-opioid therapies.

The cost of illness and economic burden of endometriosis and chronic pelvic pain in Australia: A national online survey.

INTRODUCTION: Endometriosis has a significant cost of illness burden in Europe, UK and the USA, with the majority of costs coming from reductions in productivity. However, information is scarce on if there is a differing impact between endometriosis and other causes of chronic pelvic pain, and if there are modifiable factors, such as pain severity, that may be significant contributors to the overall burden. METHODS: An online survey was hosted by SurveyMonkey and the link was active between February to April 2017. Women aged 18-45, currently living in Australia, who had either a confirmed diagnosis of endometriosis via laparoscopy or chronic pelvic pain without a diagnosis of endometriosis were included. The retrospective component of the WERF EndoCost tool was used to determine direct healthcare costs, direct non-healthcare costs (carers) and indirect costs due to productivity loss. Estimates were extrapolated to the Australian population using published prevalence estimates. RESULTS: 407 valid responses were received. The cost of illness burden was significant in women with chronic pelvic pain (Int $16,970 to $ 20,898 per woman per year) irrespective of whether they had a diagnosis of endometriosis. The majority of costs (75-84%) were due to productivity loss. Both absolute and relative productivity costs in Australia were higher than previous estimates based on data from Europe, UK and USA. Pain scores showed the strongest relationship to productivity costs, a 12.5-fold increase in costs between minimal to severe pain. The total economic burden per year in Australia in the reproductive aged population (at 10% prevalence) was 6.50 billion Int $. CONCLUSION: Similar to studies in European, British and American populations, productivity costs are the greatest contributor to overall costs. Given pain is the most significant contributor, priority should be given to improving pain control in women with pelvic pain.

National trends in inpatient endometriosis admissions: Patients, procedures and outcomes, 2006-2015.

INTRODUCTION: Despite guidance towards minimally invasive, outpatient procedures for endometriosis, many patients nonetheless receive inpatient care. Our objective was to assess trends in patient and hospital characteristics, surgical complications and hospital charges for women with an endometriosis-related inpatient admission in the United States. METHODS: We conducted a pooled cross-sectional analysis of Healthcare Cost and Utilization Project Nationwide Inpatient Sample data. Visits were stratified into three time-period-defined cohorts (2006-2007, 2010-2011, and 2014 through the first three quarters of 2015). Visits were included if the patient was aged 18-49 years and the primary diagnosis code was for endometriosis (International Classification of Diseases, 9th Revision code 617.xx). We evaluated counts of inpatient admissions and rates of patient and hospital characteristics. RESULTS: The number of inpatient admissions with a primary diagnosis code for endometriosis decreased by 72.8% from 2006 to 2015. At the same time, among those admitted for inpatient care for endometriosis, the proportions who had Medicaid insurance and multiple documented comorbidities increased. From 2006 to 2015, mean total hospital charges increased by 75% to $39,662 in 2015 US dollars, although average length of stay increased by <1 day. CONCLUSIONS: The number of inpatient admissions with a primary diagnosis of endometriosis decreased over the past decade, while surgical complications and associated hospital charges increased. The share of patients with multiple comorbidities increased and an increasing proportion of inpatient endometriosis admissions were covered by Medicaid and occurred at urban teaching hospitals. These findings suggest a demographic shift in patients receiving inpatient care for endometriosis towards more complex, vulnerable patients.

Deep endometriosis transvaginal ultrasound in the workup of patients with signs and symptoms of endometriosis: a cost analysis.

OBJECTIVE: Deep endometriosis transvaginal ultrasound (DE TVS) is accurate in the detection of ovarian endometriosis and DE; however, realisation of its full potential and utilisation remains variable. As such, patients may require a two-step surgical approach (diagnostic followed by therapeutic laparoscopy) or experience incomplete surgical treatment. Besides the clinical implications, the economic impact of a two-step approach to diagnosis and treatment on the healthcare system is likely to be significant. We aim to compare the economic costs of two diagnostic models of care for patients with potential endometriosis. DESIGN: Cost analysis using Markov model with 12-month time horizon comparing the economic costs of two diagnostic models. SETTING: The study used a hypothetical population of 1000 women visiting a public tertiary gynaecology clinic. POPULATION: Women with potential endometriosis. Estimates for endometriosis prevalence and severity were drawn from local Australian hospital data. METHODS: The conventional model (M1) includes the basic TVS and diagnostic laparoscopy. The novel model (M2) includes the DE TVS. Probabilistic sensitivity analysis was conducted to capture the uncertainty in the information used to populate the models. MAIN OUTCOME MEASURE: Changes to government, health-service and patient costs with the adoption of the DE TVS compared with standard diagnostic methods. Costs are given in Australian dollars (AU$) and also in pound sterling (£). RESULTS: The total annual cost of the novel model (M2) is AU$12,547,724.03 (£6,826,673.63), cheaper than the conventional model (M1), which cost AU$13,472,161.67 (£7,329,620.15). CONCLUSIONS: For a population of 1000 women, the integration of the DE TVS may save healthcare costs of AU$924,437 (£502,946.17) annually. TWEETABLE ABSTRACT: An endometriosis-focused ultrasound may negate a two-step surgery pathway, including diagnostic surgery, and save healthcare money.

Health Care Utilization and Costs Associated with Endometriosis Among Women with Medicaid Insurance.

BACKGROUND: Endometriosis is a painful chronic inflammatory disease caused by endometrial tissue implanting and growing outside the uterus, resulting in pelvic pain symptoms and subfertility. Treatment imposes a substantial economic burden on the patient and health care system. OBJECTIVE: To evaluate direct health care utilization and costs among women newly diagnosed with endometriosis compared with age-matched controls in a U.S. Medicaid population. METHODS: This retrospective cohort study used deidentified health care claims from the 2007-2015 MarketScan Multi-State Medicaid Database. Women (aged 18-49 years) newly diagnosed with endometriosis (ICD-9-CM 617.xx) during January 2008 through September 2014 were identified (date of first diagnosis = index date). Age-matched women without endometriosis (controls) were selected from the database and assigned index dates matching the distribution for endometriosis patients. Direct health care resource utilization (HCRU) and costs (medical and pharmacy) over the 12-month post-index period (2015 U.S. dollars) were computed by service category (hospitalization, emergency room visits, outpatient services, and prescriptions) and compared between study cohorts using the chi-square test for proportions and t-test for continuous variables. RESULTS: The final sample included 15,615 endometriosis patients and 86,829 matched controls. HCRU during the 12-month post-index follow-up period was significantly higher for endometriosis cases compared with controls in all measured categories. Hospital admissions occurred among 33.1% of cases and 7.2% of controls, and 65.8% of endometriosis patients were admitted for endometriosis-related surgery. Emergency room visits occurred in 71.5% of cases, and 42.2% of controls. Mean (SD) office visits were 10.4 (8.5) for endometriosis patients and 5.1 (6.9) for controls. Endometriosis patients had significantly more prescription claims than controls, 45.9 (42.0) versus 25.1 (39.1). Mean total direct health care costs were $13,670 ($29,843) for cases versus $5,779 ($23,614) for controls. All differences between cases and controls were significant at P < 0.001. CONCLUSIONS: Health care costs and resource utilization in all measured categories were higher among endometriosis cases than controls. The economic burden of endometriosis among patients with Medicaid insurance is substantial, underscoring the unmet medical need for earlier diagnosis and cost-effective treatments. DISCLOSURES: This study was funded by AbbVie and conducted by Truven Health Analytics, an IBM Company. AbbVie participated in developing the study design, data analysis and interpretation, manuscript writing and revisions, and approval for publication. Soliman and Vora are employees of AbbVie and may own AbbVie stock/stock options. Surrey has served in a consulting role on research to AbbVie and is on the speaker bureau for Ferring Laboratories. Bonafede and Nelson are employees of Truven Health Analytics, an IBM Company, which received compensation from AbbVie for the overall conduct of the study and preparation of the manuscript. Agarwal has served in a consulting role on research to AbbVie. Preliminary results of this study were previously presented in a podium session at the 2017 American Society for Reproductive Medicine Scientific Congress and Expo; October 28-November 1, 2017; San Antonio, TX.

Does endometriosis affect professional life? A matched case-control study in Switzerland, Germany and Austria.

OBJECTIVES: Endometriosis is a gynaecological disease most commonly causing severe and chronic pelvic pain as well as an impaired quality of life. The aim of this study was to investigate if and how endometriosis affects choices regarding professional life as well as the quality of daily working life. DESIGN, SETTING AND PARTICIPANTS: In the context of a multicentre case-control study, we collected data from 505 women with surgically/histologically confirmed diagnosis of endometriosis and 505 matched controls. Study participants were recruited prospectively in hospitals and doctors' practices in Switzerland, Germany and Austria. Using a detailed questionnaire, the study investigated work-life and career choices of study participants. MAIN OUTCOME MEASURES: Associations between endometriosis/disease symptoms and limitations in career development as well as ability to work. RESULTS: Women with endometriosis were less often able to work in their desired profession than women from the control group (adjusted OR=1.84, 95% CI: 1.15 to 2.94, R2=0.029, p=0.001) and they had to take health-related limitations into consideration in their career decisions to a significantly higher degree than women in the control group (OR=4.79, 95% CI: 2.30 to 9.96, R2=0.063, p<0.001). Among women with endometriosis, chronic pain was significantly associated with increased sick leave (OR=3.52, 95% CI: 2.02 to 6.13, R2=0.072, p<0.001) as well as with loss of productivity at work (OR=3.08, 95% CI: 2.11 to 4.50, R2=0.087, p<0.001). CONCLUSIONS: Endometriosis is associated with impairment of professional life, in particular with regard to career choices. Further research to develop strategies to support endometriosis-affected women in realising professional opportunities is recommended. TRIAL REGISTRATION NUMBER: NCT02511626; Pre-results.

Elagolix for endometriosis: all that glitters is not gold.

Elagolix, an orally active non-peptidic GnRH antagonist, has been approved by the Food and Drug Administration for the management of moderate to severe pain associated with endometriosis. As the degree of ovarian suppression obtained with elagolix is dose-dependent, pain relief may be achieved by modulating the level of hypo-oestrogenism while limiting side effects. Elagolix may thus be considered a novelty in terms of its endocrine and pharmacological properties but not for its impact on the pathogenic mechanisms of endometriosis, as the target of this new drug is, yet again, alteration of the hormonal milieu. Given the oestrogen-dependent nature of endometriosis, a reduction of side effects may imply a proportionate decrease in pain relief. Furthermore, if low elagolix doses are used, ovulation is not consistently inhibited, and patients should use non-hormonal contraceptive systems and perform serial urine pregnancy tests to rule out unplanned conception during periods of treatment-induced amenorrhoea. If high elagolix doses are used to control severe pain for long periods of time, add-back therapies should be added, similar to that prescribed when using GnRH agonists. To date, the efficacy of elagolix has only been demonstrated in placebo-controlled explanatory trials. Pragmatic trials comparing elagolix with low-dose hormonal contraceptives and progestogens should be planned to verify the magnitude of the incremental benefit, if any, of this GnRH antagonist over currently used standard treatments. The price of elagolix may impact on patient adherence and, hence, on clinical effectiveness. In the USA, the manufacturer AbbVie Inc. priced elagolix (OrilissaTM) at around $10 000 a year, i.e. $845 per month. When faced with unaffordable treatments, some patients may choose to forego care. If national healthcare systems are funded by the tax payer, the approval and the use of a new costly drug to treat a chronic condition, such as endometriosis, means that some finite financial resources will be diverted from other areas, or that similar patients will not receive the same level of care. Thus, defining the overall 'value' of a new drug for endometriosis also has ethical implications, and trade-offs between health outcomes and costs should be carefully weighed up.

Preliminary insights on the relation between endometriosis, pelvic pain, and employment.

AIMS: The economic burden of endometriosis and pelvic pain involves direct and indirect healthcare costs due to work loss and decreased productivity. However, the relation between endometriosis, pelvic pain, and employment remains underinvestigated. This study aimed at providing preliminary insights into this topic. METHODS: We compared the employment status (having vs. not having a job) in 298 consecutive endometriosis patients and in 332 women without a history of endometriosis (control group). We also examined the association between pelvic pain and employment status. RESULTS: Women with endometriosis were less likely to be employed compared to women without endometriosis (OR 0.508; 95% CI 0.284-0.908; p = 0.022). Women with symptomatic endometriosis were less likely to be employed relative to controls (OR 0.345; 95% CI 0.184-0.650; p = 0.001), as well as to asymptomatic endometriosis patients (OR 0.362; 95% CI 0.167-0.785; p = 0.01). No significant differences emerged between asymptomatic endometriosis and the control group (p > 0.05). Greater severity of dysmenorrhea, dyspareunia, chronic pelvic pain, and dyschezia was found in unemployed endometriosis patients (vs. employed endometriosis participants). CONCLUSION: Endometriosis symptoms may significantly affect women's professional life, with important socioeconomic, legal, and political implications. Community-based participatory research is encouraged.

Real-World Evaluation of Direct and Indirect Economic Burden Among Endometriosis Patients in the United States.

INTRODUCTION: The prevalence of endometriosis and the need for treatment in the USA has led to the need to explore the contemporary cost burden associated with the disease. This retrospective cohort study compared direct and indirect healthcare costs in patients with endometriosis to a control group without endometriosis. METHODS: Women aged 18-49 years with endometriosis (date of initial diagnosis = index date) were identified in the Truven Health MarketScan® Commercial database between 2010 and 2014 and female control patients without endometriosis were matched by age and index year. The following outcomes were compared: healthcare resource utilization (HRU) during the 12-month pre- and post-index periods (including inpatient admissions, pharmacy claims, emergency room visits, physician office visits, and obstetrics/gynecology visits), annual direct (medical and pharmacy) and indirect (absenteeism, short-term disability, and long-term disability) healthcare costs during the 12-month post-index period (in 2014 US$). Multivariate analyses were conducted to estimate annual total direct and indirect costs, controlling for demographics, pre-index clinical characteristics, and pre-index healthcare costs. RESULTS: Overall, 113,506 endometriosis patients and 927,599 controls were included. Endometriosis patients had significantly higher HRU during both the pre- and post-index periods compared to controls (p < 0.0001, all categories of HRU). Approximately two-thirds of endometriosis patients underwent an endometriosis-related surgical procedure (including laparotomy, laparoscopy, hysterectomy, oophorectomy, and other excision/ablation procedures) in the first 12 months post-index. Mean annual total adjusted direct costs per endometriosis patient during the 12-month post-index period was over three times higher than that for a non-endometriosis control [$16,573 (standard deviation (SD) = $21,336) vs. $4733 (SD = $14,833); p < 0.005]. On average, incremental direct and indirect 12-month costs per endometriosis patient were $10,002 and $2132 compared to their matched controls (p < 0.005). CONCLUSIONS: Endometriosis patients incurred significantly higher direct and indirect healthcare costs than non-endometriosis patients. FUNDING: AbbVie Inc.

Medical therapy for preventing recurrent endometriosis after conservative surgery: a cost-effectiveness analysis.

OBJECTIVE: To assess the cost-effectiveness of different strategies, including gonadotropin-releasing hormone agonist (GnRH-a) and oral contraceptive therapy, for the prevention of endometriosis recurrence after conservative surgery. DESIGN: Cost-effectiveness analysis from a health care perspective. SETTING: A health-resource-limited setting in China. POPULATION: Patients who underwent conservative laparoscopic or laparotomic surgery for endometriosis. METHODS: A Markov model was developed for the endometriosis disease course. Clinical data were obtained from published studies. Direct medical costs and resource utilization in the Chinese health care setting were taken into account. The health and economic outcomes were evaluated over a period from treatment initiation to menopause onset. Sensitivity analyses were carried out to test the impact of various parameters and assumptions on the model output. MAIN OUTCOME MEASURES: Quality-adjusted life years (QALYs) gained and costs from a health care perspective. RESULTS: The incremental cost-effectiveness ratio of 6-month GnRH-a therapy compared with no therapy ranged from $6,185 per QALY in deep endometriosis to $6,425 with peritoneal endometriosis. A one-way sensitivity analysis showed considerable influential factors, such as remission rates and utility values. Probabilistic sensitivity analysis indicated that 6-month GnRH-a therapy is cost-effective in most cases at a threshold of $7,400/QALY, regardless of the type of endometriosis. CONCLUSION: Six months of therapy with GnRH-a can be a highly cost-effective option for the prevention of endometriosis recurrence. TWEETABLE ABSTRACT: Gonadotropin-releasing hormone agonist is cost effective for the prevention of endometriosis recurrence.

Incremental direct and indirect cost burden attributed to endometriosis surgeries in the United States.

OBJECTIVE: To compare direct and indirect costs between endometriosis patients who underwent endometriosis-related surgery (surgery cohort) and those who have not received surgery (no-surgery cohort). DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): Endometriosis patients (aged 18-49 years) with (n = 124,530) or without (n = 37,106) a claim for endometriosis-related surgery were identified from the Truven Health MarketScan Commercial and Health and Productivity Management databases for 2006-2014. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Primary outcomes were healthcare utilization during 12-month pre- and post-index periods, annual direct (healthcare) and indirect (absenteeism and short- and long-term disability) costs during the 12-month post-index period (in 2014 US dollars). Indirect costs were assessed for patients with available productivity data. RESULT(S): Patients in the surgery cohort had significantly higher healthcare resource utilization during the post-index period and had mean annual total adjusted post-index direct costs approximately three times the costs among patients in the no-surgery cohort ($19,203 [SD $7,133] vs. $6,365 [SD $2,364]; average incremental annual direct cost = $12,838). The mean cost of surgery ($7,268 [SD $7,975]) was the single largest contributor to incremental annual direct cost. Mean estimated annual total indirect costs were $8,843 (surgery cohort) vs. $5,603 (no-surgery cohort); average incremental annual indirect cost = $3,240. CONCLUSION(S): Endometriosis patients who underwent surgery, compared with endometriosis patients who did not, incurred significantly higher direct costs due to healthcare utilization and indirect costs due to absenteeism or short-term disability. Regardless of the surgery type, the cost of index surgery contributed substantially to the total healthcare expenditure.

Randomized Trial on Fast Track Care in Colorectal Surgery for Deep Infiltrating Endometriosis.

STUDY OBJECTIVE: To study the application of a fast-track care protocol in colorectal surgery for deep infiltrating endometriosis. Bowel endometriosis is an infrequent but not rare condition that often needs intestinal surgery and imposes a high economic burden on society. DESIGN: Prospective randomized trial (Canadian Task Force classification I). SETTING: Tertiary referral center. PATIENTS: Two hundred twenty-seven patients with preoperative evidence of bowel endometriosis. INTERVENTIONS: We randomly assigned 227 patients with preoperative evidence of bowel endometriosis to a fast-track protocol (no preoperative bowel preparation, early restoration of diet, no postoperative antibiotics, and early postoperative mobilization) or conventional care for laparoscopic intestinal surgery. Randomization was obtained on a double-blind, date-based schedule, and all procedures were performed by a homogenous group of expert surgeons. Surgical outcomes and a health economic evaluation were assessed. MEASUREMENTS AND MAIN RESULTS: The primary outcome was hospital stay. Patient's well-being and intraoperative and postoperative complications up to 30 days after surgery were also assessed. Subsequently, direct medical costs were analyzed. Patients assigned to the fast-track protocol were discharged earlier (median 3 vs 7 days, p < .001) with no significant differences in subjective well-being (p = .55). Operative details, postoperative complications, and need of temporary ileostomy were similar (p = .89) between groups as well as readmission rates within 30 days (p = .69). The application of a fast-track protocol resulted in an overall significant reduction of costs (USD 6699 vs 8674, p < .01), and differences were more evident in cases of protective stoma (7652 vs 8793, p < .05) and surgery with postoperative complications (10 835 vs 14 005, p < .01). CONCLUSION: The application of a fast-track care protocol for laparoscopy in cases of pelvic and intestinal endometriosis does not increase the risk of complications and ensures a reduction of medical costs.