Leukocyte telomere length (LTL) is a biomarker of replicative history of cells and has been posited to be an indicator of biological aging. LTL may yield insight into immunomodulatory disorders, including systemic lupus erythematosus (SLE), an immune-mediated inflammatory disease that disproportionately affects Black/African American women. This study examined the association between LTL and mortality among 422 Black/African American women in the Black Women's Experiences Living with Lupus (BeWELL) Study. Participants were recruited from metropolitan Atlanta, Georgia between April 2015 and May 2017, and followed for a mean of 1.98 years (SD=0.38). LTL was measured as the telomere to single copy gene ratio (T/S). Mortality was assessed prospectively. Cox proportional hazards regression models adjusting for sociodemographic, health, and disease characteristics were specified. A total of 19 participants died during the follow-up period. Adjusting for demographic, socioeconomic, and health-related covariates, longer LTL was associated with lower risk of mortality (Hazard Ratio=0.13, 95% Confidence Interval=0.02, 0.83, P=0.03). This study is the first to report an association between LTL and subsequent mortality among Black/African American women with SLE. Findings may be particularly relevant for this population, which has been shown to experience severe disease consequences. Future research may further explore LTL in mechanistic studies of SLE and assess the utility of LTL for monitoring disease progression and outcomes.

Despite advances in targeted therapies, treatment with glucocorticoids remains a mainstay in the management of various immune-mediated diseases. High cumulative doses of exogenous glucocorticoids lead to a spectrum of side-effects, in particular increased fracture risk. Fragility fractures might result in immobility, frequent admission to hospitals, and loss of quality of life. Glucocorticoid excess impairs bone microarchitecture and bone strength and can cause multiple vertebral fractures. Fracture risk at other skeletal sites is also enhanced and triggered by an increased risk for falls. Glucocorticoid-induced osteoporosis results from direct suppression of osteoblast and osteocyte function, a transient stimulation of osteoclast formation and activity, catabolic effects on bone matrix and muscle protein, and metabolic alterations. Assessment of fracture risk using the Fracture Risk Assessment Tool (FRAX) with dual-energy X-ray absorptiometry represents the first diagnostic step; its predictive value can be improved by applying specific adjustments such as the trabecular bone score. This Review highlights how the bone microenvironment responds to supraphysiological glucocorticoid concentrations, and discusses the basis for skeletal fragility and fractures. We review the use and limitations of current and emerging imaging technologies and prediction tools, and discuss bone-forming and antiresorptive treatment strategies and their use to prevent and treat glucocorticoid-induced osteoporosis.

OBJECTIVE:Controversy persists regarding the optimal management of gout in routine primary care. There is a lack of clarity on whether treating to a target serum urate (TTT-SU) versus treating to avoid symptoms (TTASx) is more effective. METHODS:We designed a randomized controlled comparative effectiveness trial aimed at patients in primary care who have known gout, have elevated SU levels, and had at least one flare in the previous 12 months. The trial was designed to be pragmatic and incorporated structured input from primary care physicians, rheumatologists, and patients. The TTASx strategy group will receive weeklong courses of typical therapies for gout flares, such as colchicine, naproxen, or an oral glucocorticoid. The TTT-SU strategy group will receive urate-lowering therapy (primarily allopurinol) with dose titration to maintain an SU level <6 mg/dL, colchicine (or naproxen) prophylaxis for the first six months of urate-lowering therapy, and access to the same flare therapies as the TTASx group. Two clinicians (nurses or physicians) per site will be trained in each strategy to manage the patients in each arm without contamination. Gout flares are the primary outcome and are assessed every two weeks by trained study staff masked to treatment assignment using a validated questionnaire. The secondary outcome is quality of life. Blood pressure control, kidney function, glycemic control, and coronary atherosclerosis are exploratory secondary outcomes. RESULTS:Several sites have started prescreening using automated search strategies in their patients' electronic health records. Of the first 1,381 patients found in primary care practices with a history of gout, 691 patients (50%) passed prescreening checks. These potentially eligible participants have a median age of 67 years, 85% are men, median SU levels are 7.2 mg/dL, and 18% are taking low dosages of allopurinol. These patients have been targeted for recruitment efforts that are underway now. CONCLUSION:This randomized controlled active comparator strategy trial will answer a key question in the treatment of patients with gout in primary care: the comparative effectiveness of TTT-SU versus TTASx in gout. Secondary and exploratory outcomes will add important information regarding the broader extra-articular and quality-of-life effects of lowering SU levels.

Higher area socioeconomic level was associated with a decreased risk of romosozumab discontinuation during COVID-19 lockdown among U.S. Medicare beneficiaries. Patients in these areas were more likely to restart osteoporosis treatment post-discontinuation. Timely support for vulnerable patients is crucial for improving adherence during public health crises. To evaluate the association between area socioeconomic (SES) vulnerability and the discontinuation of romosozumab and the impact of the COVID lockdown on osteoporosis treatment among women enrolled in the U.S. Medicare who initiated romosozumab. Female Medicare beneficiaries aged 65 and older who initiated romosozumab between April 2019 and September 2020 were included. Discontinuation was defined as a > 60-day gap between doses. SES vulnerability was assessed using the county-level Social Vulnerability Index SES theme. A Discontinuation Risk Score (DcRS) was calculated to control for individual characteristics. A Cox proportional hazards model evaluated the association between county SES and discontinuation. Secondary analyses examined treatment restart within six months post-discontinuation. The study included 6,777 new romosozumab users. Higher area SES level (lower vulnerability) was associated with a reduced risk of discontinuation during the COVID-19 lockdown (adjusted HR = 0.79 [0.68, 0.92] for the highest vs. lowest SES). Of 2,937 patients who discontinued, 1,816 restarted osteoporosis treatments within 6 months, including 661 switching to other medications. Patients in the highest SES group were more likely to restart osteoporosis treatment during lockdown (adjusted HR = 1.14 [1.01—1.30]) comparing with the lowest SES group, which is primarily driven by treatment switch (adjusted HR = 1.30 [1.06—1.60]). Medicare beneficiaries in counties with higher SES level (lower vulnerability) were less likely to discontinue romosozumab during the COVID-19 lockdown and more likely to switch treatments if discontinued, resulting in shorter treatment gaps. Providing timely support to vulnerable patients is vital for maintaining treatment adherence during future public health emergencies.

Disclosure: R.J. Auchus: Has been involved in contracted research with companies such as Neurocrine Biosciences/Neurocrine UK, LTD, Spruce Biosciences, Corcept Therapeutics, Crinetics Pharmaceuticals, Recordati Rare Diseases, Adrenas Therapeutics, and Mineralys Pharmaceuticals, Served as consultant for organizations like Quest Diagnostics, Corcept Therapeutics, Xeris Pharmaceuticals, Crinetics Pharmaceuticals, Novo Nordisk, Neurocrine Biosciences/Neurocrine UK, LTD, Recordati Rare Diseases, H Lundbeck A/S, Sparrow Pharmaceuticals, Astellas Pharmaceuticals, and Acerand Therapeutics. O. Hamidi: Advisory board member for Neurocrine Biosciences, Corcept Therapeutics, Recordati Rare Diseases, Crinetics Pharmaceuticals, Inc, Camurus, Xeris Pharmaceuticals, Inc, Educational speaking engagement with Recordati Rare Diseases. I. Bancos: None. K. Saag: Recieved grants or contracts from Amgen, Arthrosi, Horizon, LG Pharma, Radius, and Olatec, Received consulting fees from Amgen, Anthrosi, Atom Bioscience, Horizon, LG Pharma, Angitia, and Gruenthal. H. Falhammar: None. U. Srirangalingam: Consulting fees from Crinetics Pharmaceuticals, Diurnal Ltd and H Lundbeck A/S. M. Calanchini: None. E. Jen: Full-time employee of Neurocrine Biosciences, Inc. V.H. Lin: Full-time employee of Neurocrine Biosciences, Inc. J. Sturgeon: Full-time employee of Neurocrine Biosciences, Inc. J.L. Chan: Full-time employee of Neurocrine Biosciences, Inc. Background: Crinecerfont, a corticotropin releasing factor type 1 receptor (CRF1) antagonist, is a first-in-class medication that is FDA-approved for adjunctive treatment to glucocorticoid (GC) replacement to control androgens in patients with classic congenital adrenal hyperplasia (CAH). In the Phase 3 CAHtalyst™ Adult study (NCT04490915), crinecerfont (100 mg BID) significantly reduced adrenal androgens, enabling substantial GC dose reductions from Day 1 baseline (BL) at the end of double-blind placebo-controlled (DBPC) treatment at Week 24, with a least-squares (LS) mean percent change of -27.3% vs. -10.3% for placebo (LS mean difference [LSMD] -17.0%, P<0.0001). At the end of open-label (OL) treatment at Month 12, mean percent decreases from BL in GC dose were -24.6% in participants who continued on crinecerfont (CFT/CFT) and -29.7% in those who switched from placebo (PBO/CFT). Objective: To evaluate clinical outcomes in adults with CAH who received up to 1 year of crinecerfont, in the context of substantial GC dose reductions. Methods: Outcomes related to excess adrenocorticotropic hormone (ACTH)/androgens (e.g., hirsutism in female participants) and GC exposure (e.g., body mass index [BMI], insulin resistance, hyperlipidemia) were analyzed at the end of DBPC treatment (Week 24) and the end of OL treatment (Month 12). DBPC outcomes with P-values are presented as LS mean changes with LSMD. Results: In female participants, mean hirsutism visual analog scale scores (out of 0 [no symptoms] to 100 [very severe symptoms]) were 40.6 (crinecerfont) and 37.4 (placebo) at BL. Changes from BL at end of DBPC (Week 24) and OL (Month 12) were: Week 24 (-9.8 for crinecerfont [n=58] vs -2.8 placebo [n=27], LSMD -7.0, P=0.1564); Month 12 (-11.5 CFT/CFT [n=56], -12.9 PBO/CFT [n=27]). Mean BMI at BL was 30.1 kg/m2 (crinecerfont) and 29.0 kg/m2 (placebo). Changes from BL were: at Week 24 (-0.4 vs. -0.02 for crinecerfont [n=118] vs. placebo [n=57], LSMD -0.40, P=0.1068); at Month 12 (-0.8 CFT/CFT [n=114], -0.4 PBO/CFT [n=56]). Mean homeostatic model assessment of insulin resistance values were high at BL (crinecerfont 3.2, placebo 3.0). Changes from BL were: at Week 24 (-0.6 vs. -0.4 for crinecerfont [n=61] vs placebo [n=29], LSMD -0.29, P=0.3454); at Month 12 (-0.5 CFT/CFT [n=107], -0.9 PBO/CFT [n=54]). Mean values for cholesterol (total, LDL, and HDL) and triglycerides were within normal range or near optimal at BL and remained stable. Conclusion: Adults with CAH who received up to 1 year of crinecerfont continued to show improvements in BMI and insulin resistance, as expected with lower GC doses. Moreover, despite substantial GC dose reductions, hirsutism in female participants improved with crinecerfont. Given the known adverse effects of ACTH/androgen excess and chronic supraphysiologic GC exposure, these results represent a promising therapeutic advancement in CAH. Presentation: Sunday, July 13, 2025

Primary care physicians (PCPs) play a critical role in the management of gout worldwide. However, significant gaps in gout care persist, underscoring the need for improved approaches to its management. While some guidelines, such as those from the American College of Physicians (ACP) published in 2016, support a more reactive treat-to-symptoms approach, others from the American College of Rheumatology (ACR) and the European Alliance Of Associations For Rheumatology advocate for a proactive treat-to-target (TTT) strategy—focused on achieving optimal serum urate levels through urate lowering therapy (ULT). This divergence reflects differing clinical priorities and differential interpretation of the evidence and it may contribute to variability in care delivery. Improving gout management requires greater engagement from both patients and healthcare providers, with particular emphasis on increasing adherence to ULT. Patients need enhanced support to better understand the importance of sustained urate lowering treatment, while healthcare providers may benefit from clearer guidance aligned with evidence-based strategies to foster greater patient trust and confidence. This article provides an overview of the current state of guidelines, highlights areas of agreement and discordance between them, and identifies key areas for improving care delivery. It additionally offers insight into alternative care delivery strategies, such as those involving non-physician health professionals, which have shown promise in enhancing patient outcomes. Future research should focus on continued development of innovative, multi-modal interventions to improve ULT adherence, including health system-based initiatives and collaborative care models.

OBJECTIVE:Gout follow-up after an emergency department (ED) visit for gout flare may improve outcomes, which could be influenced by demographics and social determinants of health. We aimed to determine the factors associated with outpatient gout follow-up within our health care system within 6 months following an ED visit for a gout flare. METHODS:This historical cohort study was conducted at an academic medical center that includes 3 EDs and 1 urban urgent care. Among patients with a gout flare during their ED visit, we determined the presence/absence of an outpatient visit for gout within 6 months of the ED visit. We reported the proportion of patients who received outpatient gout follow-up. We used multivariable logistic regression to test the association between key covariates and outpatient follow-up for gout. RESULTS:From September 2021 to August 2022, we analyzed 159 patients with gout flare at the ED visit, of whom 56 (35.2%) had an outpatient visit addressing gout within 6 months. Being married (odds ratio [OR], 2.66; confidence interval [CI], 1.25-5.68; p = 0.01), absence of comorbidities (OR, 3.86; CI, 1.01-14.71; p = 0.048), use of colchicine at the ED visit or discharge (OR, 2.67; CI, 1.18-6.02; p = 0.02), and increased age (OR, 1.44; CI, 1.15-1.82; p = 0.002, for each 5-year increase) were associated with increased odds of gout follow-up. CONCLUSIONS:Among a cohort of patients seeking urgent/emergent care for gout flare, only one-third followed up for gout in the outpatient setting. Modifiable factors such as colchicine prescription use were associated with gout follow-up, which may represent areas to target in future studies focused on promoting improved outpatient follow-up for gout.

BACKGROUND:Gout is a chronic disease of monosodium urate crystal deposition caused by elevated serum urate (SU). Gout may progress from acute episodic attacks to a disabling chronic deforming arthropathy. Allopurinol and febuxostat are the most widely prescribed urate-lowering drugs, however, these agents have potential adverse events and are seldom titrated to achieve a target SU level. Tigulixostat is a novel non-purine selective xanthine oxidase inhibitor for gout with hyperuricemia which has demonstrated potent in vitro and in vivo urate lowering activity and is being further investigated in humans for regulatory approvals. METHODS:The Phase 3 program for tigulixostat consists of two clinical trials: EURELIA 1 and EURELIA 2. EURELIA 1 is a randomized, multi-regional, double-blind, parallel-group, placebo-controlled study to assess the safety and efficacy of 6 months of tigulixostat (100, 200, or 300 mg) in gout patients with hyperuricemia (n = 350). EURELIA 2 is a randomized, multi-regional, double-blind, double-dummy, parallel-group, active comparator (allopurinol titrated up to 800 mg) and placebo-controlled study to assess the safety and efficacy of tigulixostat (100, 200, or 300 mg) up to 12 months in gout patients with hyperuricemia (n = 2542). The primary endpoint for both studies is to determine the proportion of patients with SU levels <6.0 mg/dL sustained at for 3 months (Months 4, 5, and 6). CONCLUSIONS:EURELIA 1 and EURELIA 2 studies will be able to adequately determine the efficacy and safety of tigulixostat compared to both placebo and allopurinol. TRIAL REGISTRATION NUMBER:For EURELIA 1, the clinicaltrials.gov identifier is NCT05586958. For EURELIA 2, the clinicaltrials.gov identifier is NCT05586971 and the EU CT number is 2022-501421-20-00. The sponsor for both trials is LG Chem, Ltd. (Seoul, South Korea).

OBJECTIVES:We tested whether a rheumatology telemedicine visit was noninferior to an in-person visit for patient satisfaction and care effectiveness, including for subgroups of age, sex, race and ethnicity, income, and employment status. METHODS:This multicenter noninferiority trial randomised patients to 1 in-person or telemedicine visit. The primary outcome was the proportion of high visit satisfaction (9 or 10 on a 0-10 scale). The primary analysis tested whether patient satisfaction with telemedicine was noninferior to in-person care (10% noninferiority margin). Secondary and exploratory outcomes included preference for next visit type, satisfaction in subgroups, and immunosuppressant toxicity monitoring. We performed modified intent-to-treat (mITT) and per-protocol analyses. RESULTS:Among 651 randomised patients (in-person, n = 323; telemedicine n = 328), 500 (76.8%) had a visit defining the mITT population. Satisfaction with telemedicine was not noninferior to in-person; 77.0% telemedicine, 90.1% in-person, difference 13.1% (90% CI, 7.7%-18.5%). Per-protocol analysis results were consistent. More participants in the in-person group compared with those in telemedicine preferred the same visit type for their next visit vs a different visit type/no preference (55.6% in-person, 19.1% telemedicine, P < .0001, mITT analysis). Men were equally satisfied with both visit types (90.0%), while women were more likely to be satisfied with in-person visits (90.2% vs 74.7%). Toxicity monitoring rates were higher in in-person vs telemedicine (eg, hepatic function: 92.1% vs 66.3%, P = .0001, per-protocol analysis). CONCLUSIONS:Among a large group of diverse patients, satisfaction with telemedicine was not noninferior to in-person rheumatology visits. More participants preferred in-person visits in the mITT and per-protocol analyses. Appropriate toxicity monitoring was lower in telemedicine vs in-person groups.

Background. Hyperuricemia and gout are associated with poor outcomes in kidney transplant (KT) recipients, including graft failure. The PROspective sTudy of pEglotiCase in Transplant patients (PROTECT) trial showed high urate-lowering efficacy of pegloticase in immunosuppressed KT recipients with uncontrolled gout. Here, we report serial dual-energy computed tomography (DECT) findings in PROTECT participants. Methods. KT recipients with uncontrolled gout (serum urate [SU] ≥7 mg/dL, refractory to/intolerant of oral urate-lowering therapy, and symptoms [≥2 flares per year, tophi, and/or gouty arthritis]) and serial DECT imaging were included. Patients were required to have an estimated glomerular filtration rate ≥15 mL/min/1.73 m2 >1 y posttransplant. All patients received pegloticase for ≤24 wk (8 mg infusion every 2 wk) and underwent imaging (screening, week 14, week 24). DECT images were acquired with standard protocols and postprocessed for monosodium urate (MSU) volume (VMSU) using default settings. Regions (bilateral hands/wrists, feet/ankles, knees) with paired screening/week 24 images and screening VMSU ≥0.5 cm3 (minimized DECT-artifact influence) were included. Results. Eight patients underwent DECT imaging (all men; age: 52.3 ± 11.2 y, time since KT: 18.7 ± 6.9 y, estimated glomerular filtration rate: 45.6 ± 12.4 mL/min/1.73 m2, SU: 10.4 ± 2.1 mg/dL). Six patients (75%) completed the study and received 24 wk of pegloticase therapy, and 2 prematurely discontinued because of COVID-exposure concerns. Of the 6 patients, 4 met imaging inclusion criteria and were included in the analysis. All 4 patients had sustained SU-lowering during month 6 with marked VMSU reduction at week 24 (mean change in VMSU: –98.9%±1.7% [5 imaging regions]). Numerous bone erosions were present in all patients with MSU-adjacent, unknown mineral deposit-adjacent, and deposit-independent erosions. Imaging suggested osteopenia/osteomalacia in 5 patients (83%). After pegloticase treatment, MSU-adjacent erosions decreased in size in a single patient with no DECT evidence of osteopenia/osteomalacia. Conclusions. Consistent with prior studies in nontransplant populations, marked depletion of deposited MSU occurred in KT recipients with uncontrolled gout after pegloticase therapy. However, unlike transplant-naive patients, subsequent bone erosion remodeling was not widely observed in urate-adjacent erosions, perhaps due to overall poor bone health in this patient population. Clinical Trial Registration. ClinicalTrials.gov: NCT04087720.

Epidural steroid injections (ESIs) are a common and often effective treatment for radicular back pain. While oral glucocorticoids increase fracture incidence, little is known regarding fracture risk after ESI. This study investigated the incidence of fractures among individuals who received ESI and those who did not. We hypothesized that ESI exposure would be associated with an increased incidence of osteoporotic fractures and specifically vertebral fractures. Using 2005-2018 5% Medicare data, individuals with radicular pain who had ≥1 ESI and those who did not (non-ESI) were matched 1:10 by age, sex, and month of radicular pain diagnosis using exposure density sampling (EDS). Using a high-dimensional propensity score (HDPS) calculated based on the top 500 covariates across multiple data dimensions, ESI and non-ESI individuals were matched 1:1. Fractures were identified using validated ICD-9/10 diagnosis codes. Fracture incidence rate (IR) was calculated by group, and hazard ratios (HR) compared using Cox regression. 25 062 ESI patients and 221 735 non-ESI patients who met eligibility criteria were identified using EDS. Mean age was 76 yr (74% female). Among ESI-treated individuals, there were 2296 fractures, IR 49.1 (95% CI: 47.2-51.2) per 1000 person yr. For non-ESI individuals, there were 11 917 fractures, IR 35.2 (95% CI: 34.5-35.8). Individuals who received ESI had a greater hazard of fracture at typical osteoporotic sites, HR 1.39 (95% CI 1.33-1.46) by EDS and 1.32 (1.12-1.54) by HDPS, and a greater hazard of vertebral fracture, 1.54 (1.45-1.64) by EDS and 1.69 (1.38-2.07) by HDPS. Patients who received greater cumulative ESI doses (≥3 in 1 yr) had a higher risk of fractures within the first 6 mo of follow-up. ESI exposure in older individuals is associated with an increased risk of fracture, suggesting there may be lasting detrimental skeletal effects of ESI. Further research into strategies to reduce fracture risk in this population is warranted.

Osteoporosis in men is an underdiagnosed and undertreated condition that leads to significant morbidity and mortality, particularly in the aging population. This consensus report provides tailored guidelines for diagnosing, preventing, and treating male osteoporosis in the Asia–Pacific region by integrating global best practices with regional adaptations. To establish evidence-based, region-specific guidelines for the management of male osteoporosis in the Asia–Pacific region, addressing demographic and lifestyle factors. Expert feedback was gathered through premeeting reviews, consensus conferences, and collaborative discussions. A life-course approach was employed to align international best practices with Asia–Pacific-specific needs, emphasizing continuous monitoring and intervention from middle age onward. The 12 consensus strategies systematically approach male osteoporosis management, addressing screening, diagnosis, treatment, and long-term follow-up. Recommendations include the assessment of fracture risk for men aged 50 years and above, use of dual-energy X-ray absorptiometry (DXA) testing for men aged 70 years and above, lifestyle modifications, and pharmacological interventions such as bisphosphonates, denosumab, and anabolic agents for high-risk patients. Secondary causes of osteoporosis were highlighted, along with the establishment of fracture liaison services (FLSs) to improve long-term care. A life-course approach was proposed to optimize bone health throughout men’s lives. This consensus provides a comprehensive framework tailored to the Asia–Pacific region for diagnosing, preventing, and managing osteoporosis in men. By addressing region-specific challenges and promoting evidence-based interventions, the latest guidelines incorporating the consensus may depict the conceptual direction in reducing fracture risk and improving long-term bone health outcomes for osteoporosis in men.