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Objective: Gout is associated with a higher risk of fracture; however, findings on the associations of hyperuricemia and urate‐lowering therapy (ULT) with the risk of fracture have been inconsistent. We examined whether lowering serum urate (SU) levels with ULT to a target level (i.e., <360 μmoles/liter) reduces the risk of fracture among individuals with gout. Methods: We emulated analyses of a hypothetical target trial using a "cloning, censoring, and weighting" approach to examine the association between lowering SU with ULT to the target levels and the risk of fracture using data from The Health Improvement Network, a UK primary care database. Individuals with gout who were age 40 years or older and for whom ULT was initiated were included in the study. Results: Among 28,554 people with gout, the 5‐year risk of hip fracture was 0.5% for the "achieving the target SU level" arm and 0.8% for the "not achieving the target SU level" arm. The risk difference and hazard ratio for the "achieving the target SU level" arm was –0.3% (95% confidence interval [95% CI] –0.5%, –0.1%) and 0.66 (95% CI 0.46, 0.93), respectively, compared with the "not achieving the target SU level" arm. Similar results were observed when the associations between lowering SU level with ULT to the target levels and the risk of composite fracture, major osteoporotic fracture, vertebral fracture, and nonvertebral fracture were assessed. Conclusion: In this population‐based study, lowering the SU level with ULT to the guideline‐based target level was associated with a lower risk of incident fracture in people with gout. [ABSTRACT FROM AUTHOR]

Background: Two recent randomized clinical trials of escalating doses of allopurinol for the progression of chronic kidney disease (CKD) reported no benefits but potentially increased risk for death. Whether the risk could occur in patients with gout and concurrent CKD remains unknown.Objective: To examine the relation of allopurinol initiation, allopurinol dose escalation, and achieving target serum urate (SU) level after allopurinol initiation to all-cause mortality in patients with both gout and CKD.Design: Cohort study.Setting: The Health Improvement Network U.K. primary care database (2000 to 2019).Participants: Patients aged 40 years or older who had gout and concurrent moderate-to-severe CKD.Measurements: The association between allopurinol initiation and all-cause mortality over 5-year follow-up in propensity score (PS)-matched cohorts was examined. Analysis of hypothetical trials were emulated: achieving target SU level (<0.36 mmol/L) versus not achieving target SU level and dose escalation versus no dose escalation for mortality over 5-year follow-up in allopurinol initiators.Results: Mortality was 4.9 and 5.8 per 100 person-years in 5277 allopurinol initiators and 5277 PS-matched noninitiators, respectively (hazard ratio [HR], 0.85 [95% CI, 0.77 to 0.93]). In the target trial emulation analysis, the HR of mortality for the achieving target SU level group compared with the not achieving target SU level group was 0.87 (CI, 0.75 to 1.01); the HR of mortality for allopurinol in the dose escalation group versus the no dose escalation group was 0.88 (CI, 0.73 to 1.07).Limitation: Residual confounding cannot be ruled out.Conclusion: In this population-based data, neither allopurinol initiation, nor achieving target SU level with allopurinol, nor allopurinol dose escalation was associated with increased mortality in patients with gout and concurrent CKD.Primary Funding Source: Project Program of National Clinical Research Center for Geriatric Disorders. [ABSTRACT FROM AUTHOR]

Objective: Observational data facilitate examination of treatment-effect heterogeneity, but the risk of bias is substantial. The present study was undertaken to highlight methodologic considerations through an analysis of whether smoking affects response to tumor necrosis factor inhibitors (TNFi) in axial spondyloarthritis (SpA).Methods: We used longitudinal data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis. Participants fulfilling the Assessment of SpondyloArthritis international Society criteria for axial SpA who started their first TNFi were eligible for analysis. In comparing the impact of smoking status, weighted generalized estimating equations were used to examine changes in several continuous outcome measures, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS). Inverse probability weights were used to account for differences in baseline covariates and excluded participants. We separately assessed response in the first 3 months to account for nonrandom dropout.Results: For 840 participants who started on TNFi, 1,641 assessments from 627 individuals were analyzed (69% male, mean age 46 years). A total of 33% were current smokers and 30% ex-smokers. Ex-smokers and current smokers had worse disease than never smokers at baseline. Accounting for these differences, response did not differ according to smoking status. Compared to never smokers, ex-smokers (β = -0.6, 95% confidence interval [95% CI] -1.4, 0.3) and current smokers (β = -0.4, 95% CI -1.1, 0.4) had a similar response according to the BASDAI and ASDAS (ex-smokers β = -0.1, 95% CI -0.5, 0.3; current smokers β = -0.01, 95% CI -0.4, 0.4) at 3 months.Conclusion: TNFi response did not differ according to baseline smoking status in this UK cohort. Conflicting results from previous studies were likely due to methodologic differences. This analysis highlights potential sources of bias that should be addressed in future studies. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to compare comorbidities and biologic DMARD (bDMARD) use between AS and non-radiographic axial SpA (nr-axSpA) patients, using a large cohort of patients from routine clinical practice in the United States. Methods We performed a cross-sectional study using electronic medical records from two academic hospitals in the United States. Data were extracted using automated searches (⩾3 ICD codes combined with text searches) and supplemented with manual chart review. Patients were categorized into AS or nr-axSpA according to classification criteria. Disease features, comorbidities (from a list of 39 chronic conditions) and history of bDMARD prescription were compared using descriptive statistics. Results Among 965 patients identified, 775 (80%) were classified as having axSpA. The cohort was predominantly male (74%) with a mean age of 52.5 years (s. d. 16.8). AS patients were significantly older (54 vs 46 years), more frequently male (77% vs 64%) and had higher serum inflammatory markers than those with nr-axSpA (median CRP 3.4 vs 2.2 mg/dl). Half of all patients had at least one comorbidity. The mean number of comorbidities was 1.5 (s. d. 2.2) and similar between AS and nr-axSpA groups. A history of bDMARD-use was seen in 55% of patients with no difference between groups. The most commonly prescribed bDMARDs were adalimumab (31%) and etanercept (29%). Ever-prescriptions of individual bDMARDs were similar between AS and nr-axSpA. Conclusion Despite age differences, nr-axSpA patients had similar comorbidity burdens as those with AS. Both groups received comparable bDMARD treatment in this United States clinic-based cohort. [ABSTRACT FROM AUTHOR]

• SII is associated with 2-year all-cause mortality in elderly hip fracture patients. • There is a U-shaped association between SII and 2-year all-cause mortality. • SII can serve as a biomarker to identify patients at high-risk for death. To assess the association between systemic immune-inflammation index (SII) and 2-year all-cause mortality in elderly patients with hip fractures. We performed a cohort study of hip fracture patients aged 65 years or older who received hip fracture surgery at a tertiary hospital from January 2005 to March 2022. The SII was calculated as: SII = (neutrophil count * platelet count) / lymphocyte count, based on the latest blood test before discharge. Patients were categorized into 3 groups according to SII tertiles: low SII group (≤770.92 × 109/L), medium SII group (770.92 × 109/L -1293.03 × 109/L), and high SII group (>1293.03 × 109/L). The primary outcome was 2-year all-cause mortality. We evaluated the association between SII and 2-year all-cause mortality using the multivariate Cox regression model. Among 2766 patients, 296 patients died during the 2-year follow-up period. The incidence of 2-year all-cause mortality per 1000 persons was 90.0 (95 % CI: 73.2–110.2) in the low SII group, 86.8 (95 % CI: 70.3–106.7) in the medium SII group, and 144.3 (95 % CI: 123.1–168.5) in the high SII group. Compared with patients in the low SII group, the hazard ratio for 2-year all-cause mortality was 0.97 (95 % CI: 0.69–1.37) in the medium SII group and 1.47 (95 % CI: 1.07–2.01) in the high SII group (P for trend, 0.010). SII is significantly associated with 2-year all-cause mortality in elderly patients with hip fracture. SII may be used to identify patients at high risk of mortality after hip fracture surgery. [ABSTRACT FROM AUTHOR]