BACKGROUND Uterine fibroids are hormone-responsive neoplasms that are associated with heavy menstrual bleeding. Elagolix, an oral gonadotropin-releasing hormone antagonist resulting in rapid, reversible suppression of ovarian sex hormones, may reduce fibroidassociated bleeding. METHODS We conducted two identical, double-blind, randomized, placebo-controlled, 6-month phase 3 trials (Elaris Uterine Fibroids 1 and 2 [UF-1 and UF-2]) to evaluate the efficacy and safety of elagolix at a dose of 300 mg twice daily with hormonal "add-back" therapy (to replace reduced levels of endogenous hormones; in this case, estradiol, 1 mg, and norethindrone acetate, 0.5 mg, once daily) in women with fibroid-associated bleeding. An elagolix-alone group was included to assess the impact of add-back therapy on the hypoestrogenic effects of elagolix. The primary end point was menstrual blood loss of less than 80 ml during the final month of treatment and at least a 50% reduction in menstrual blood loss from baseline to the final month; missing data were imputed with the use of multiple imputation. RESULTS A total of 412 women in UF-1 and 378 women in UF-2 underwent randomization, received elagolix or placebo, and were included in the analyses. Criteria for the primary end point were met in 68.5% of 206 women in UF-1 and in 76.5% of 189 women in UF-2 who received elagolix plus add-back therapy, as compared with 8.7% of 102 women and 10% of 94 women, respectively, who received placebo (P<0.001 for both trials). Among the women who received elagolix alone, the primary end point was met in 84.1% of 104 women in UF-1 and in 77% of 95 women in UF-2. Hot flushes (in both trials) and metrorrhagia (in UF-1) occurred significantly more commonly with elagolix plus addback therapy than with placebo. Hypoestrogenic effects of elagolix, especially decreases in bone mineral density, were attenuated with add-back therapy.

Background/Aims: To estimate the prevalence of diagnosed endometriosis (DE) in women in the United States and assess the associated symptomatic burden. Methods: An online, cross-sectional survey of women aged 18-49 years was conducted from August 6, 2012, through November 14, 2012. Survey data (weighted by age, race, education, income, geographical distribution, and propensity score) were used to estimate the prevalence and symptomatic burden of DE in women in the United States. Weighted logistic regressions were used to assess differences in symptom burden between women with and without endometriosis. Results: The prevalence of DE was estimated at 6.1% (2,922 of 48,020 women surveyed); 52.7% of women were 18-29 years of age when they were diagnosed with endometriosis. Most (86.2%) women experienced symptoms before diagnosis. More women with (vs. without) DE had menstrual pelvic pain/cramping (52.7 vs. 45.2%), non-menstrual pelvic pain/cramping (36.7 vs. 14.3%), infertility (11.6 vs. 3.4%), and dyspareunia (29.5 vs. 13.4%). Women with endometriosis were also more likely to report severe symptoms (OR (95% CI) 2.7 (2.3-3.1) for menstrual pelvic pain/cramping, 2.2 (1.7-2.9) for non-menstrual pelvic pain/cramping, and 2.4 (1.8-3.2) for dyspareunia). Conclusion: The prevalence of DE among US women is notable, and affected women experience a substantial symptom burden.

Experiencing endometriosis symptoms is associated with lower HRQL. Importantly, as symptom severity and number of symptoms increase, HRQL further deteriorates.

Introduction:The clinical benefits of biologic and oral treatments for moderate-to-severe plaque psoriasis are well-established, but efficacy outcomes can vary across therapies. Comparative efficacy analysis can be highly informative in clinical settings with multiple therapeutic options. This study assessed the short-term and long-term comparative efficacy of biologic and oral treatments for moderate-to-severe psoriasis. Methods: A systematic literature review identified phase 2/3/4 randomized controlled trials (RCTs) through to 1 July 2020 for Food and Drug Administration-or European Medicines Agency-licensed treatments for moderate-tosevere psoriasis. Psoriasis Area and Severity Index (PASI) 75/90/100 response rates at the end of the primary response (short-term: 10--16 weeks from baseline) and maintenance periods (long-term: 48-52 weeks from baseline) were estimated using Bayesian network metaanalysis. Surfaces under the cumulative ranking curves (SUCRA) were estimated to present the relative ranking of treatments. Results: In the short term (N = 71 RCTs), the PASI 90 response rates were highest for ixekizumab (72.

NCT01441635.

This study was funded by AbbVie, which also develops the oral GnRH antagonist elagolix (in collaboration with Neurocrine Biosciences) for the management of endometriosis and uterine fibroids. A.M.S. is an employee of AbbVie and currently owns AbbVie stocks. H.Y., E.X.D. and C.K. are employees of Analysis Group, Inc., which has received consultancy fees from AbbVie. C.W. is a Clinical Professor at the Department Obstetrics and Gynecology at Georgetown University in Washington, DC, USA and has served in a consulting role to AbbVie for this project.

IntroductionThe 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.MethodsWomen 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.ResultsOverall, 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).ConclusionsEndometriosis patients incurred significantly higher direct and indirect healthcare costs than non-endometriosis patients.FundingAbbVie Inc.Electronic supplementary materialThe online version of this article (10.1007/s12325-018-0667-3) contains supplementary material, which is available to authorized users.

Background:The comparative safety and benefit-risk profiles of moderate-to-severe psoriasis treatment have not been well studied.Objective: To compare the short-term (12-16 weeks) and long-term (48-56 weeks) safety and benefit-risk profiles of moderate-to-severe psoriasis treatments.Methods: A systematic literature review of phase II-IV randomized controlled trials of moderate-to-severe psoriasis treatments was conducted (cutoff: July 1, 2020). Any adverse events (AEs), any serious AEs, and AEs leading to treatment discontinuation were compared using Bayesian network meta-analyses (NMAs).Results: Fifty-two and 7, respectively, randomized controlled trials were included in the short-and longterm NMAs, respectively. In the short-term NMA, the rates of any AEs were the lowest for tildrakizumab (posterior median: 46.0%), certolizumab (46.2%), and etanercept (49.1%). The rates of any serious AE were the lowest for certolizumab (0.8%), risankizumab (1.2%), and etanercept (1.6%). The rates of AEs leading to treatment discontinuation were the lowest for risankizumab (0.5%), tildrakizumab (1.0%), and guselkumab (1.5%). In the long-term NMA, risankizumab had the lowest rates of all 3 outcomes (67.5%, 4.4%, and 1.0%, respectively) and the most favorable benefit-risk profile. Limitations:The results may not be generalizable to real-world populations.Conclusions: Antieinterleukin 23 agents were associated with low rates of safety events. Risankizumab had the most favorable benefit-risk profile in the long term.