The Environmental Law Institute (ELI) is a non-profit, non-partisan organization, headquartered in Washington, D.C., that seeks to "make law work for people, places, and the planet" through its work as an environmental law educator, convener, publisher, and research engine. ELI's primary audience includes legal practitioners, business leaders, land managers, land use planners, environmentalists, journalists, and lawmakers. The Institute also convenes conferences to promote the exchange of ideas; holds seminars to educate legal practitioners and business leaders; and publishes original research, both as monographs and in its periodicals, the Environmental Law Reporter and The Environmental Forum..
1001 Background: Imlunestrant (imlu) is a next-generation, brain-penetrant, oral selective estrogen receptor degrader. The EMBER-3 trial, in patients (pts) with ER+, HER2- ABC who had disease progression on or after aromatase inhibitor-based therapy, showed significant progression free survival (PFS) improvement with imlu vs standard therapy (SOC, fulvestrant or exemestane) in pts with ESR1 mutations ( ESR1 m), and with imlunestrant+abemaciclib (imlu+abema) vs imlu in all pts, regardless of ESR1 m. Exploratory PRO analyses are presented here. Methods: EORTC QLQ-C30 was administered at baseline (BL) and every 8 weeks until treatment discontinuation. Prespecified QLQ-C30 analysis used a longitudinal mixed model for repeated measures to calculate mean change from BL in pts with BL and ≥1 post-BL score. PRO-CTCAE (diarrhea frequency) was administered weekly, reporting 0 (never) to 4 (almost constantly). PRO-CTCAE (injection site reaction [ISR]) was administered to fulvestrant recipients weekly for 2 weeks post-injection, reporting yes/no (pain, swelling, redness). Descriptive analysis was used for PRO-CTCAE. Results: In pts with ESR1 m, imlu monotherapy was associated with many improved or maintained EORTC QLQ-C30 scores, whereas scores with SOC were declined or maintained. Specifically, pts with ESR1 m on imlu had improved global health status (GHS)/quality of life (QOL) and physical function (PF) scores, while scores with SOC declined (mean change differences between treatments: 9.9 [0.1, 19.7] and 6.2 [-0.8, 13.1], respectively). These PRO findings mirror the PFS findings in this group. In the overall population, GHS/QOL scores declined similarly with imlu vs SOC (mean change differences: 0.5 [-4.7, 5.7]), while PF scores were maintained with imlu vs a slight decline with SOC (mean change difference: 2.5 [-1.1, 6.1]). Most fulvestrant recipients (72%) reported ISR at any time while on treatment, with a mean of 31% during the first week of the first 6 cycles. Imlu+abema vs imlu showed broadly similar declines in all pts, with minimal mean change differences in GHS/QOL and PF scores (0.8 [-7.4, 5.9]; -2.2 [-6.6, 2.2], respectively). Pts reported similarly low rates of “frequent” or “almost constant” diarrhea with imlu (3%) and SOC (2%) and higher rates with imlu+abema (22%). Conclusions: PROs from EMBER-3 demonstrated that patients with ESR1 m had better GHS/QOL and PF with imlu vs SOC, mirroring efficacy results. While the frequency of CTCAE defined ISRs was low, the high rate of PRO-CTCAE ISR demonstrates that this clinically relevant adverse event is underappreciated by physicians. Additionally, all pts had generally comparable GHS/QOL and PF with imlu+abema vs imlu. Overall, these results support the efficacy and safety of imlu compared to existing SOC. Clinical trial information: NCT04975308 .
Offshore fresh or freshened groundwater (OFG) is an important but under-represented component of coastal hydrogeological and climate systems. Recent advances in geophysical imaging, offshore drilling, numerical modelling, and machine learning have improved understanding of OFG distribution, dynamics, and connectivity with onshore aquifers. Remaining challenges include volumetric quantification, recharge history, ecological implications, and governance. OFG may complement coastal water-resource portfolios, but sustainable utilisation requires integrated management, environmental safeguards, and updated legal frameworks at national and international levels.
Abstract Background/Aims Psoriasis vulgaris (PsO) and psoriatic arthritis (PsA), (together, psoriatic disease [PsD]) are chronic inflammatory conditions that significantly impair quality of life (QoL). Obesity is a prevalent condition amongst people with PsD. Comorbid obesity and PsD can exacerbate each other. Weight control is vital for improving health outcomes for patients with PsD, which can be achieved through diet, exercise, medications, and surgery. The real-world experiences of individuals receiving advanced therapies for PsD and overweight/obesity, with the more recently approved incretin hormones remain largely unexplored.This study qualitatively summarized the experiences of adults with PsD and overweight/obesity receiving concomitant treatment for both conditions. Methods Adults with PsD and overweight/obesity were invited to participate in a survey followed by virtual semi-structured interviews. Eligible participants self-reported taking a biologic or advanced therapy for PsD for ≥1 year, initiating an incretin hormone ≥3 months after PsO/PsA treatment, and using it for at least 6 months but no longer than 12 months to mitigate recall bias. Interview transcripts were coded for emergent concepts using NVivo v12.0, and thematic analysis was conducted to assess patterns across responses. Results Twenty U.S. adults (PsO and PsA:N=9; PsO only:N=6, PsA only:N=5) were recruited from market research panels (N = 19) and the National Psoriasis Foundation (N = 1). Participants (mean age: 50±12.4; 60% female) discussed impaired QoL across physical health and social engagement (100%), daily functioning (90%), and mental health (90%) prior to initiating incretin hormone therapy. Joint pain (50%) and skin symptoms (35%) were cited as most distressing symptoms during interviews. Participants primarily initiated incretin hormone therapy to lose weight (90%), with 20% seeking improvement in PsD symptoms. Following initiation, all reported physical health improvements, including weight loss (95%), PsO/PsA symptom relief (90%), and improved ability to exercise (80%). Participants discussed improvements in mental health, ability to perform daily activities, and social engagement. Most participants (60%) initiated the conversations about weight-loss medications with their healthcare providers; 40% recalled providers discussing the potential connection between PsD and weight. Many (80%) wished these discussions had occurred earlier, with 25% specifically wishing these occurred at PsO/PsA diagnosis. Additionally, 30% sought for more information from providers about weight-loss treatment options. Four key themes were identified: 1) impact of living with PsD and overweight/obesity before weight-loss medications was largely negative; 2) weight-loss medications contributed to meaningful improvements in QoL, including physical and mental health; 3) individuals wanted more interaction and information from providers of weight-loss medications and PsD; and 4) individuals perceived a relationship between weight and health, but not always between weight and PsD. Conclusion Individuals with PsD and overweight/obesity reported physical health and QoL improvement after incretin hormone therapy. Early and proactive provider engagement around PsD and weight management options may enhance health outcomes. Disclosure U. Desai: Corporate appointments; Employee of Analysis Group. B. Mitchell: Corporate appointments; Employee and shareholder of Eli Lilly and Company. A. Cohee: Corporate appointments; Employee and shareholder of Eli Lilly and Company. Y. Wang: Corporate appointments; Employee of Analysis Group. A. Holub: Corporate appointments; Employee of Analysis Group. M. Mattera: Corporate appointments; Employee of Analysis Group. E. Sears: Corporate appointments; Employee of Analysis Group. C. Bakewell: Consultancies; Novartis, Lilly, Pfizer, Johnson & Johnson, AbbVie, Sanofi, Sobi, BMS, UCB. T. Bhutani-Jacques: Corporate appointments; Owner and CEO of Synergy Health. N. Kirson: Corporate appointments; Employee of Analysis Group. H. Stuckey-Peyrot: None. J. Swift: Corporate appointments; Employee and shareholder of Eli Lilly and Company.
Rationale: Obstructive sleep apnea (OSA) is a breathing disorder associated with cardiovascular comorbidity and mortality. Obesity represents a major modifiable risk factor for OSA. SURMOUNT-OSA is a master protocol guiding 2 placebo-controlled trials investigating the efficacy and safety of tirzepatide in participants with OSA and obesity. Each trial had the primary endpoint of change in apnea-hypopnea index (AHI) measured by laboratory polysomnography (PSG).1 In this pre-specified analysis of SURMOUNT-OSA, we also report the change in peripheral apnea-hypopnea index (pAHI) measured using WatchPAT, a home sleep study device which uses peripheral arterial tone technology, and the corresponding change in body weight. Methods: SURMOUNT-OSA master protocol guided two double-blind, randomized, placebo-controlled phase 3 clinical studies including participants with moderate-to-severe OSA and obesity to determine the efficacy and safety of once-weekly (QW) tirzepatide at the maximum tolerated dose (MTD). Study 1 included those unable or unwilling to use PAP therapy and Study 2 included those on PAP therapy at study entry. WatchPAT measurements were collected at Week 0, 4, 12, 20, and 52 for participants in Study 1 (n=117 at baseline, n=59 assigned to tirzepatide and n=58 on placebo). The mixed model repeated measures (MMRM) statistical analysis was conducted based on the data points from modified intent-to-treat (mITT) participants, collected on treatment and not on PAP for Study 1. Results: Figure 1 shows the change from baseline in pAHI and percent change from baseline in body weight for participants in Study 1. A statistically significant change in pAHI versus placebo was observed from Week 20, namely, Week 4 (-2.2, p=0.455), Week 12 (-6.5, p=0.064), Week 20 (-10.8, p<0.001) and Week 52 (-15.1, p<0.001) in participants treated with tirzepatide. Even with a smaller sample size (n=31 and n=32 for tirzepatide and placebo at Week 52, respectively), the effect size is comparable to previously reported PSG data collected at baseline, Week 20 and Week 52.1 Reductions in pAHI with tirzepatide treatment were accompanied by a statistically significant and clinically relevant decreases in body weight at all timepoints measured (p<0.001 versus placebo). Conclusions: Treatment with tirzepatide reduced pAHI in participants with moderate-to-severe OSA and obesity as early as in Week 4 after treatment initiation, with statistical significance from Week 20. Reductions in pAHI were accompanied by a statistically significant decrease in body weight. 1. Malhotra, A. et al. Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity. N Engl J Med 2024;391:1193-1205.
Background: Baricitinib (Bari), an oral, selective, Janus kinase inhibitor, is approved for severe alopecia areata (AA) in adults and is being studied in children. Methods: BRAVE-AA-PEDS is a phase 3 trial of pediatric subjects (6 to <18 years [y]) with severe AA (Severity of Alopecia Tool [SALT] score ≥50); BRAVE-AA1 and -AA2 are trials in adults. In BRAVE-AA-PEDS (adolescents, 12 to <18y) and BRAVE-AA1/AA2, subjects were randomly assigned to once-daily Bari 4mg, Bari 2mg, or placebo. Primary endpoint was % of patients with SALT score ≤20 at Week (W) 36. We compared baseline (BL) characteristics and W36 efficacy and safety in adolescents (N=257) vs adults (N=1200). Results: BL characteristics of adolescents and adults, respectively: female, 49.4% vs 60.7%; mean age(y), 14.7 vs 37.5; mean onset age(y), 7.9 vs 25.3, mean disease duration(y), 6.4 vs 12.2; mean current AA episode duration(y), 3.2 vs 3.9; BL SALT score 95-100, 63.8% vs 53.2%. In adolescents and adults, respectively, SALT score <20 was achieved by 42.4% vs 34% of patients on Bari 4mg, 27.4% vs 19.7% on Bari 2mg, and 4.5% vs 4.1% on placebo. Of patients with BL SALT score 50-94, 68% of adolescents vs 48% of adults achieved the primary endpoint. Common adverse events: headache, acne, and upper respiratory tract infection. Conclusion: Bari is effective and safe for severe AA in both adolescents and adults. Adolescents had higher W36 response rates despite higher BL severity, suggesting benefits of early intervention.
