BACKGROUND:Metabolic syndrome (MetSyn) is associated with frailty in older adults, with few data among midlife women. We examined MetSyn, including duration, for associations with the development of prefrailty and frailty. METHODS:The Study of Women's Health Across the Nation is a multiethnic, longitudinal cohort study of women aged 42-52 years at the time of enrollment (1996-1997). MetSyn was measured longitudinally, using ATP III criteria, starting at baseline. Pre-frailty and frailty were measured at two later visits (2012/13 and 2015/16) using Fried criteria. Associations of pre-frailty and frailty with prevalent MetSyn, the cumulative number of prior visits with MetSyn, and individual MetSyn criteria were examined using multivariable models. RESULTS:A total of 1769 women were included (mean age 59.7 years, SD 3.3). The adjusted odds ratios (aOR) for having pre-frailty or frailty in women with MetSyn compared to those without were 2.77 (95% CI, 2.19-3.50) and 8.73 (95% CI, 5.89-12.95), respectively. Each additional visit a woman met criteria for MetSyn was associated with a higher odds of pre-frailty and frailty (aOR 1.20; 95% CI: 1.14-1.26, and aOR: 1.41; 95% CI: 1.33-1.50, respectively). Individual MetSyn criteria were also associated with the risk of frailty. CONCLUSIONS:Among women in this multiethnic cohort, MetSyn was common during midlife and strongly associated with future development of pre-frailty and frailty while women were in their early 60s. Measurement of MetSyn during midlife can help identify women at high risk for developing frailty early in the aging process.

Adoption of mobile health applications (“apps”) that collect patient-reported outcomes (PROs) into clinical practice remains limited, and studies about patient usage preferences are lacking. Our aim was to characterize adherence to a PRO app designed for patients with rheumatoid arthritis (RA). We performed a post hoc analysis of a non-randomized trial of a PRO app for patients with RA seen at an academic medical center. The 12-month trial enrolled 149 participants with RA. The app collected one of four PROs every other day. We calculated adherence using two methods: (1) percent of PROs completed, and (2) time until app non-use. These calculations used different intervals for PRO completion and different periods of non-use to define adherence. We also investigated the association of potential predictors on the outcome using multivariable regression models. The percentage of completed PROs was 43.5

BACKGROUND:Chronic kidney disease is a common comorbidity of rheumatoid arthritis. Because there has been scarce and conflicting evidence on the use of biological and targeted synthetic therapy in patients with rheumatoid arthritis and chronic kidney disease, we aimed to examine the effectiveness and persistence of biological and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) for patients with rheumatoid arthritis and chronic kidney disease. METHODS:This multicentre, prospective cohort study used data from the CorEvitas Rheumatoid Arthritis registry on patients with rheumatoid arthritis who initiated each type of biological and targeted synthetic DMARD (TNF inhibitors, CTLA4 immunoglobulin, IL-6 inhibitors, B-cell depletion therapy, and JAK inhibitors) recruited from 160 rheumatology practices in the USA. Patients were required to have moderate or high disease activity according to the Clinical Disease Activity Index (CDAI; score >10). Chronic kidney disease was defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1·73 m2 at biological or targeted synthetic DMARD initiation. The primary outcome was the attainment of remission according to CDAI score. Propensity scores were used for overlap weighting to improve the balance of characteristics for patients with and without reduced eGFR. Cox regressions estimated the unadjusted and adjusted hazard ratio (HR) of reduced eGFR for CDAI-based remission. People with lived experience of rheumatoid arthritis were not involved in the study design or conduct. FINDINGS:Between Oct 1, 2001, and Dec 31, 2023, 12 123 biological and targeted synthetic DMARD treatment initiations in 9601 patients with rheumatoid arthritis, with 51 931 person-years of follow-up, were identified. Of 12 123 eligible biological and targeted synthetic DMARD treatment initiations, 10 857 (89·6%) were in patients with preserved eGFR and 1266 (10·4%) were in patients with reduced eGFR. Across both groups, median age was 59·0 years (IQR 50·0-67·0), 9720 (80·2%) of 12 123 treatment initiations were in female patients and 2403 (19·8%) were in male patients, and 9908 (81·7%) were in non-Hispanic White patients. 3025 (27·9%) of 10 857 treatment initiations in patients with preserved eGFR resulted in CDAI-based remission versus 246 (19·4%) of 1266 treatment initiations in patients with reduced eGFR. Reduced eGFR was associated with a lower likelihood of attaining CDAI-based remission (unadjusted HR 0·71 [95% CI 0·62-0·82], adjusted HR 0·76 [0·66-0·88]) compared with preserved eGFR. INTERPRETATION:Although biological and targeted synthetic DMARDs are generally well tolerated and effective options, patients with rheumatoid arthritis and reduced eGFR have lower likelihood of attaining remission. Tailored treatment strategies for this high-risk population should be established. FUNDING:National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Objective Most trials in gout focus on serum urate changes because assessing gout flares is difficult. We evaluated the reliability of an electronic, self-reported gout flare assessment compared to a staff-conducted telephone questionnaire.Methods A convenience sample of participants from the Treat-to-Target Serum Urate Versus Treat-to-Avoid Symptoms in Gout (TRUST) randomized clinical trial, which examines gout flares as a primary outcome, completed biweekly electronic surveys reporting gout flares. Study staff blinded to treatment assignment conducted a gout flare assessment at standard biweekly telephone visits to confirm electronic reports. We assessed agreement between flare assessment modalities using multiple assessments such as percent agreement, Cohen's kappa, Gwen's AC1 statistic, McNemar's test of equivalence, and intraclass correlation coefficient (ICC). In addition, we accounted for repeated measures within patients using mixed effects models, presenting a mixed effects ICC. Where necessary, 95% confidence intervals were calculated using nonparametric bootstrapping.Results A total of 28 patients (mean age 60.5 years, SD 13; 93% male) participated in the 12-week pilot, completing 109 flare periods with 108 electronic and 99 phone assessments. Patients reported 23 flares on electronic surveys and 22 flares on phone surveys. We observed a raw percent agreement between survey types of 96%. All measures of agreement consistently demonstrated strong concordance, with an ICC of 0.880 and a mixed effects ICC of 0.746.Conclusion The pilot study shows strong agreement between electronic and telephone gout flare assessments across multiple equivalence tests, supporting electronic surveys as an accurate and efficient alternative to phone assessments.

OBJECTIVE:Hyperuricemia (HU) and gout are common in postmenopausal women. We aimed to identify the longitudinal changes in serum urate (SU) levels during and after the menopausal transition and its interaction with coexisting SU-modifying conditions. METHODS:This longitudinal study included Japanese women who underwent annual medical examinations from April 2004 to September 2024 and had at least one visit before and after self-reported menopause. Menopausal transition stages were categorized into premenopause, perimenopause (5 years before and up to the menopause), and postmenopause. Longitudinal changes in SU and HU (SU ≥6.8 mg/dL or taking medications for gout or HU) were examined by interrupted time-series analyses and evaluated across stratified subgroups. RESULTS:We analyzed 8,169 eligible participants with 93,511 visits over a median follow-up of 13.8 years. SU levels gradually increased during premenopause, rose sharply over perimenopause, and stabilized in postmenopause. Compared to premenopause, the mean SU level was 0.41 mg/dL (95% confidence interval: 0.38-0.43) higher in postmenopause. HU prevalence increased from <1.0% during premenopause to 4% to 5% during postmenopause. Compared to premenopause, the associations of a low estimated glomerular filtration rate (<60 mL/min per 1.73 m2) and a high body mass index (≥25) with HU were greater in postmenopause; HU was observed in approximately 18% of overweight or obese women at menopause. CONCLUSION:SU levels rapidly increase during perimenopause and are already elevated by the time of menopause. Maintaining a normal body weight and preserving kidney function before menopause may decrease postmenopausal HU and potentially prevent subsequent gout in women.

OBJECTIVES:The objective of this paper is to examine whether patients with newly diagnosed rheumatoid arthritis (RA) can discontinue prednisolone after short-term bridging therapy. METHODS:Patients naïve to disease-modifying antirheumatic drugs with recent-onset RA in the ARCTIC (Aiming for Remission in rheumatoid arthritis: a randomised trial examining the benefit of ultrasound in a Clinical TIght Control regimen) trial were followed for 24 months, with initial methotrexate monotherapy and prednisolone bridging therapy (tapering doses from 15 mg to 0 over 7 weeks). We explored the proportion of patients successfully discontinuing prednisolone, defined as no prednisolone use after bridging therapy, and for at least 4 subsequent months. Discontinuation was assessed after cessation of bridging therapy at 2, 3, 6, 12, 20, and 24 months. Additionally, we examined how many patients used prednisolone continuously for ≥3 months. RESULTS:Of 230 patients, 227 started prednisolone bridging therapy and were included for analyses. At baseline, mean (SD) age was 52 (13.7) years, mean (SD) disease activity score was 3.47 (1.17), 62% patients were female, and 82% patients were anticitrullinated peptide antibody positive. After 7 weeks, 84% (191/227) had discontinued prednisolone, 89% (203/227) had discontinued at 3 months, and 95% (216/227) within 24 months. Five percent (11/227) used prednisolone at every visit. The median number of days (IQR) of prednisolone use during 2 years was 55 (48-90). Among those who discontinued after 7 weeks, 80% (152/191) did not restart prednisolone. Continuous use for at least 3 months was observed in 22%. CONCLUSIONS:In newly diagnosed patients with RA using bridging therapy when starting methotrexate, over 80% successfully discontinued prednisolone. This supports that tapering to discontinuation is achievable in most patients after short-term bridging with prednisolone, in line with current European Alliance of Associations for Rheumatology recommendations.

OBJECTIVE:Studying rare diseases requires assembling robust, correctly classified cohorts. We compared the performance of seven published International Classification of Diseases, Ninth Revision (ICD-9) and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) code rule-based algorithms in the electronic health record (EHR) to identify cases of idiopathic inflammatory myopathies (IIM). METHODS:We identified patients seen at a multihospital academic medical center with one or more ICD-9 or ICD-10 codes for IIM (2000-2024). From this cohort, a random sample of 250 cases was selected for chart review for IIM based on the 2017 EULAR/American College of Rheumatology IIM classification criteria. Review was performed by two reviewers and adjudicated by a third. The performance of the algorithms was compared against (1) definite and (2) definite and probable cases of IIM. Positive predictive value (PPV), specificity, sensitivity, and negative predictive value were calculated. RESULTS:Of 250 charts, 87 definite and 28 probable IIM cases were identified. The algorithm with the highest PPV (84%) relied on ICD 9/10 codes obtained during hospitalizations but excluded ≥80% of cases with a sensitivity of 14%. Use of two or more ICD codes ≤60 days apart obtained the second highest PPV (79%) and identified 82 cases. Use of two or more ICD codes between 30 and 365 days apart obtained the third highest PPV (78%). These top-performing algorithms included definite and probable cases of IIM. CONCLUSION:Several rule-based ICD code algorithms had PPVs ranging from 77% to 84% but had lower sensitivity (14%-63%). Limitations of this study include modifications to some of the original algorithms. Future algorithms may benefit from incorporating additional EHR data and natural language processing methods.

OBJECTIVES:Clonal haematopoiesis of indeterminate potential (CH), somatic genetic mutations conferring stem cells selective advantage, are associated with increased inflammatory cytokine production, cardiovascular disease (CVD), and malignancy. We investigated whether CH was related to risk of rheumatoid arthritis (RA), an inflammatory autoimmune disease. METHODS:Within the UK Biobank, we studied 186,577 unrelated individuals with baseline data collection, genome-wide genotyping, whole exome sequencing (WES) read for CHIP, and linked general practice (GP) data for identification of incident RA in follow-up. We excluded those with prevalent RA or taking RA medications at baseline. We tested for associations between variant allele fraction (VAF) >2% and >10% for the 8 most common CHIP mutations in the general population, and incident RA, identified by billing code algorithms. Cox regression models estimated hazard ratios (HR, 95% confidence interval) for incident RA. RESULTS:594 participants developed incident RA over median follow-up 7.1 years (IQR 6.4-8.0); median time to RA was 3.9 years (IQR 2.0-5.6). Incident RA cases were slightly older at enrolment, more likely to be female, have smoked, have higher body mass index (BMI), and have prevalent CVD, and hypercholesterolaemia at baseline. However, there was no difference in the presence of CHIP mutations at baseline; 6.3% vs. 6.4% of those who did and did not develop incident RA in follow-up had any CHIP mutation at >2% VAF. CONCLUSIONS:Common CHIP mutations, including TET2, TP53, and SF3B1 mutations, were not associated with risk of incident RA when restricted to those with most complete general outpatient and hospital record follow-up in the UK Biobank.

RATIONALE & OBJECTIVE:Creatinine-based estimated glomerular filtration rate (eGFRcr) and cystatin C-based eGFR (eGFRcys) may be inaccurate for patients with rheumatoid arthritis (RA) due to sarcopenia and inflammation. This study characterized changes in eGFRcys and eGFRcr after 2 RA treatment regimens and their association with RA disease activity biomarkers. STUDY DESIGN:Secondary observational analysis of randomized controlled trial of tumor necrosis factor (TNF) inhibitor plus methotrexate (MTX) versus triple therapy (MTX, sulfasalazine, and hydroxychloroquine). SETTING & PARTICIPANTS:Patients with active RA enrolled at multiple US institutions into an immunomodulatory treatment trial. EXPOSURE:RA disease activity biomarkers. OUTCOME:eGFRcys and eGFRcr at baseline and weeks 6, 18, and 24. ANALYTICAL APPROACH:Describing eGFRcys and eGFRcr at baseline and during the follow-up period in the overall cohort and by treatment arm. Adjusted mixed-effects linear models to estimate the associations of RA activity biomarkers with eGFR. RESULTS:The study included 157 eligible trial participants (median age, 58 years; 75% female). At baseline, the mean eGFRcys was lower than the eGFRcr (63.3 vs 84.2; difference, -20.9 mL/min/1.73 m2 [95% CI, -24.7 to -17.0]). Over 24 weeks, neither eGFRcys nor eGFRcr changed overall (1.74 mL/min/1.73 m2 [95% CI, -0.77 to 4.24] and -0.28 mL/min/1.73 m2 [95% CI, -3.71 to 3.15], respectively). Multiple disease activity biomarkers, including vascular cell adhesion protein 1, interleukin 6, tumor necrosis factor receptor 1 (TNFR1), leptin, and resistin, were inversely associated with eGFRcys and/or eGFRcr at baseline in adjusted models. During the follow-up period, only TNF-RI change was inversely associated with eGFRcys change (-2.91 mL/min/1.73 m2 [95% CI, -4.48 to -1.33]) in adjusted models whereas no biomarker change was significantly related to eGFRcr change. LIMITATIONS:No measured GFR, a relatively short follow-up period, and potential false discovery because of the large number of associations examined. CONCLUSIONS:Among patients with actively treated RA, eGFRcys is consistently lower than eGFRcr. Overall, neither eGFRcys nor eGFRcr demonstrated a significant change following RA treatments, despite reductions in disease activity biomarkers. Further studies incorporating directly measured GFR are warranted. PLAIN-LANGUAGE SUMMARY:Rheumatoid arthritis (RA) is a chronic inflammatory joint disease that can also affect the kidneys. Doctors often check kidney function using blood tests for creatinine or cystatin C, but inflammation and RA medications may influence these tests differently. We studied patients with RA who began either a conventional drug combination (triple therapy) or a tumor necrosis factor (TNF) inhibitor. We measured kidney function and inflammation markers over a 6-month period after the treatment. We found that both cystatin C-based and creatinine-based estimates of kidney function were unchanged overall. An analysis of trial participants who received triple therapy showed an increase in cystatin C-based kidney function, along with a decrease in 1 inflammatory biomarker, TNF receptor 1 (TNFR1); however, the creatinine-based estimates remained unchanged. Understanding how RA treatment and inflammation affect kidney function tests may help develop better ways to monitor kidney function in people with inflammatory diseases.

Objectives: The association between age of rheumatoid arthritis (RA) onset and joint erosions remains unclear. We investigated the effects of age of RA onset on incident joint erosion and the progression of radiographic findings. Methods: Patients diagnosed with RA within 2 years of enrollment in a large single-center RA registry were included. The age of RA onset was categorized into young- (<= 44 years of age), middle- (45-65), and late-onset (>= 66). Modified total Sharp scores (mTSS) were obtained at baseline, year 2, and year 5, and incident joint erosion was defined as an erosion score >0. Adjusted odds ratio (aOR) of incident joint erosions and adjusted change in mTSS by age category were evaluated over a 5-year follow-up period. Results: Among 1,581 participants with RA, 284 patients within 2 years of RA diagnosis were identified. The mean mTSS were 0.54 in the young-, 3.12 in the middle-, and 4.77 in the late-onset group. The aOR of incident joint erosion in the middle-, aOR 4.0 (95 % CI 2.2 - 7.5), and the late-onset groups, 8.2 (95 % CI 3.6 - 19.2), were elevated compared with the young-onset group. Compared with the young-onset group, the adjusted changes in mTSS in the middle- group, 2.8 (95 % CI 0.20 - 5.4), and the late-onset groups, 1.9 (95 % CI -0.26 - 4.1), were elevated. Conclusion: The odds of incident joint erosion and change in the mTSS were increased among patients with later RA onset. Age of RA onset should be considered when determining optimal management strategies.

OBJECTIVE:Calcium pyrophosphate deposition (CPPD) disease is associated with an increased risk for cardiovascular (CV) events. We examined the atherosclerotic burden by coronary artery calcium (CAC) scores (Agatston score) and compared 10-year atherosclerotic CV disease (ASCVD) risk scores in patients with vs without chondrocalcinosis, a radiographic marker of CPPD. METHODS:We performed a cross-sectional analysis at an academic medical centre, 1991-2022. Among all patients with an Agatston score in routine care, we defined a cohort with chondrocalcinosis detected before the CAC scan. Comparators without chondrocalcinosis were matched 2:1 on age and sex-the primary analysis excluded statin users. We compared Agatston scores between the chondrocalcinosis cohort and comparators. We also tested for differences between cohorts in 10-year ASCVD risk score frequencies (low, borderline/intermediate or high). RESULTS:756 patients with chondrocalcinosis were matched to 1554 comparators (mean age 68 years, 53% female). CV risk factor burden was high in both cohorts, and statin use was infrequent. The unadjusted Agatston score was non-significantly higher in the chondrocalcinosis cohort (mean 359.1, s.d. 737.9) than in matched comparators (mean 297.1, s.d. 644.9) (P = 0.08). High 10-year ASCVD risk scores were significantly more common in the chondrocalcinosis cohort than comparators (P < 0.01). CONCLUSION:Coronary atherosclerosis burden by CAC was not significantly different between patients with chondrocalcinosis and matched comparators, though 10-year ASCVD risk scores were higher in the chondrocalcinosis cohort, suggesting that factors beyond coronary artery calcification contribute to the increased CV event rate in patients with CPPD disease.

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.

Increased fracture risk has been reported in patients using selective serotonin reuptake inhibitors (SSRIs). However, prior studies have had limited information regarding BMD and symptoms of depression, both potentially important confounders. We examined a longitudinal cohort of women who initiated SSRIs, other antidepressant (AD) medications, or no AD to estimate the risk of fracture associated with start of SSRIs. The Study of Women’s Health Across the Nation (SWAN) is a longitudinal cohort of diverse women from across the US transitioning across the menopause. Study visits are approximately yearly, with reporting of medication use, fracture incidence (any and non-traumatic), mental health scales (CES-D), and BMD (the latter occurring in selected SWAN sites). We estimated fracture incidence and relative risk among women starting SSRIs or other AD, and compared them with women not starting SSRIs or other AD. Multivariable Cox regression models with increasing adjustment were constructed. As well, secondary analyses focused on non-traumatic fractures and women with BMD measurements. The Study of Women’s Health Across the Nation includes 3302 total women, of which 286 were excluded because of prevalent AD use and 1167 because they did not have adequate follow-up time, had a fracture prior to start of an AD, or could not be matched; this left 1849 women for analysis. The incidence rates for any fracture (per 100 person-years) for SSRI users was 2.64 (95% CI: 1.82-3.71), other AD users 0.80 (95% CI: 0.22-2.04), and non-users 1.21 (95% CI: 1.07-1.36). Fully adjusted regression models found an increased hazard ratio for any fracture among women starting SSRIs compared with no AD (HR 1.77, 95% CI: 1.15-2.74). These results were consistent for non-traumatic fractures and in subgroups with BMD included as a covariate. Initiation of SSRI among women in mid-life was associated with an increased risk of fracture.