Young Ho Lee

Objectives: Hyperuricemia and gout are common but underappreciated comorbidities in Type 2 diabetes (T2D), obesity and chronic kidney disease (CKD). We aimed to quantify the pooled effects of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) and dual glucose‐dependent insulinotropic polypeptide (GIP)/GLP‐1 receptor agonists on serum uric acid (SUA), incident gout and hyperuricemia, and to determine whether these effects vary by drug class and are mediated by weight loss. Methods: We searched PubMed/MEDLINE, Embase, CENTRAL and ClinicalTrials.gov through July 2026 for RCTs of ≥ 12 weeks' duration reporting SUA change, gout flares or hyperuricemia incidence. Random‐effects meta‐analysis, subgroup and sensitivity analyses and meta‐regression were performed. Registered with PROSPERO (CRD420261468511). Results: Eighteen RCTs (77 942 participants) met inclusion criteria. Incretin‐based therapy significantly reduced SUA versus control (weighted mean difference [WMD] −0.44 mg/dL, 95% CI −0.52 to −0.35), reduced incident gout flares (hazard ratio [HR] 0.62, 95% CI 0.53–0.72), and reduced hyperuricemia incidence (odds ratio [OR] 0.61, 95% CI 0.53–0.70). Dual GIP/GLP‐1 RA (tirzepatide) produced greater SUA lowering than mono GLP‐1 RAs (−0.62 vs. −0.35 mg/dL, p = 0.001). Body‐weight loss was a significant moderator of SUA reduction ( β = −0.041 mg/dL per kg, p < 0.001), explaining 84.7% of between‐trial heterogeneity, with a significant weight‐independent intercept (−0.19 mg/dL, p < 0.001). The SUA reduction was robust in all sensitivity analyses, including restriction to placebo‐controlled trials. GRADE certainty was high for SUA and moderate for gout flares (owing to small‐study effects) and hyperuricemia incidence. Conclusion: Incretin‐based therapies were associated with modest reductions in SUA and with a lower incidence of gout flares and hyperuricemia, an effect largely related to weight loss. The clinical relevance of these effects, and the mechanism of any weight‐independent component, remains uncertain and warrant confirmation in dedicated trials.

Objective: This study aimed to assess the relationship between the neutrophil-to-lymphocyte ratio (NLR) and systemic lupus erythematosus (SLE), with specific focus on the association between NLR and disease activity, including lupus nephritis (LN), and evaluating the correlation between NLR and the SLE Disease Activity Index (SLEDAI). Methods: A systematic search of MEDLINE, Embase, and Web of Science from database inception through August 2025 was conducted. Meta-analyses compared NLR values between SLE patients and healthy controls, between active and inactive SLE, and between active LN and non-LN subgroups, with stratification by ethnicity, sample size, and publication year. Correlation coefficients between NLR and SLEDAI were pooled to assess the strength of this association. Results: Thirty-one studies comprising 4,006 SLE patients and 2,576 healthy controls were included. The combined analysis showed significantly increased NLR in SLE patients versus controls (SMD = 1.051, 95% CI = 0.817–1.286, p < 0.001). Significantly higher NLR was observed in European, Asian, and Arab SLE patients relative to healthy controls within each respective subgroup, by showing significantly higher NLR in European (SMD = 1.058, 95% CI = 0.402–1.713, p = 0.002), Asian (SMD = 1.058, 95% CI = 0.839–1.278, p < 0.001), and Arab (SMD = 1.127, 95% CI = 0.707–1.547, p < 0.001) populations. Comparing disease activity, active SLE patients had notably higher NLR than those with inactive disease (SMD = 1.134, 95% CI = 0.252–2.017, p = 0.012). However, the difference in NLR between active LN and non-LN groups was not statistically significant (SMD = 0.467, 95% CI = −0.045–0.979, p = 0.074). NLR showed a significant positive correlation with SLEDAI (correlation coefficient = 0.354, 95% CI = 0.256–0.444, p < 0.001). Subgroup analysis revealed significant correlations in Asian (correlation coefficient = 0.358, 95% CI = 0.246–0.461, p < 0.001) and Arab (correlation coefficient = 0.525, 95% CI = 0.382–0.644, p < 0.001) populations. Conclusions: This meta-analysis demonstrates that NLR is significantly increased in SLE patients compared to healthy controls, and that NLR is associated with greater disease activity, supported by its positive correlation with SLEDAI.

Introduction: This study was designed to assess the comparative efficacy and safety of telitacicept and belimumab in adult patients diagnosed with systemic lupus erythematosus (SLE). Methods: We systematically searched MEDLINE, Embase, and Web of Science from database inception through March 2026 to identify retrospective observational studies comparing telitacicept and belimumab in adult patients with SLE. A meta-analysis was conducted to pool efficacy data, reporting odds ratios (ORs) and 95% confidence intervals (CIs) for treatment response. The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO; Registration No. CRD420261420984). Results: Out of 215 records screened, 5 studies (676 patients; 340 receiving telitacicept and 336 receiving belimumab) met the inclusion criteria following full-text assessment. Telitacicept was associated with significantly improved rates of lupus low disease activity state (LLDAS) at 24 weeks (OR = 1.87, 95% CI = 1.03–3.39, p = 0.041; 2 studies, I2 = 0%, p = 0.92) and complete renal response at 24 weeks (OR = 2.38, 95% CI = 1.10–5.15, p = 0.027; 2 studies, I2 = 0%, p = 0.88) compared to belimumab, utilizing fixed-effects models due to absence of heterogeneity. The Systemic Lupus Erythematosus Responder Index-4 (SRI-4) response at 24 weeks (OR = 2.02, 95% CI = 1.04–3.91, p = 0.038; 1 study) and complete renal response at 52 weeks (OR = 2.67, 95% CI = 1.17–6.09, p = 0.019; 1 study) were also significantly greater with telitacicept. Prednisone tapering to ≤7.5 mg/day at 24 weeks approached statistical significance (OR = 1.56, 95% CI = 1.00–2.43, p = 0.049; 1 study). Analysis of safety endpoints showed no statistically significant differences between groups for overall adverse events (OR = 1.21, 95% CI = 0.96–1.53, p = 0.088; 3 studies, I2 = 0%, p = 0.95), or serious adverse events (OR = 0.68, 95% CI = 0.43–1.08, p = 0.072; 2 studies, I2 = 0%, p = 0.89). Conclusion: Telitacicept suggests greater efficacy over belimumab in achieving LLDAS, SRI-4 response, complete renal response, and reduction in prednisone dosage in patients with SLE, without notable differences in rates of adverse events, serious adverse events, or infections.

Background: Gout is a systemic inflammatory disorder increasingly associated with cardiovascular comorbidities. However, its potential relationship with atrial fibrillation (AF), especially in young adults, has not been fully delineated. To investigate the association between gout and incident AF in a large nationwide cohort of Korean adults aged 20–39 years. Methods: This retrospective cohort study analyzed 6,506,721 individuals from the Korean National Health Insurance Service (NHIS) database. Gout and AF were identified using ICD-10 codes M10 and I48, respectively. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident AF after adjusting for demographic, lifestyle, and clinical factors. Results: During a median follow-up of 12.59 years, gout was associated with a significantly increased risk of AF (fully adjusted HR, 1.44; 95% CI, 1.31–1.58). The cumulative incidence of AF was significantly higher in the gout group (log-rank P < .001). Subgroup analyses demonstrated stronger associations among non-obese individuals and those with chronic kidney disease (CKD). Conclusions: Gout was associated with an increased risk of atrial fibrillation among young adults. These findings suggest that gout may serve as a clinically relevant risk marker for AF, underscoring the need for proactive cardiovascular risk assessment in this population.

Introduction: Anifrolumab, a type I interferon receptor antagonist, has shown effectiveness in treating moderate-to-severe systemic lupus erythematosus (SLE). To fully understand its long-term efficacy, glucocorticoid (GC)-sparing potential, and cumulative safety profile in everyday clinical practice, it is essential to combine up to 4 years of long-term extension (LTE) trial data with emerging real-world evidence (RWE). Methods: A systematic literature search was performed across major electronic databases to identify phase 2/3 randomized controlled trials (RCTs), LTE studies, and RWE cohorts assessing anifrolumab in SLE. Comparative odds ratios (ORs) for RCTs were calculated using the Mantel-Haenszel method, while pooled proportions for single-arm RWE cohorts were estimated using a random-effects model. Primary outcomes included BICLA response, Lupus Low Disease Activity State (LLDAS), GC reduction (to ≤7.5 mg/day), and herpes zoster (HZ) incidence. Results: Ten studies were included, comprising phase 2/3 RCTs, their LTEs (TULIP-LTE, MUSE-LTE), and four European RWE cohorts. In the RCTs (N = 1,093), anifrolumab significantly improved BICLA responses compared to placebo (pooled OR 1.85, 95% CI 1.42–2.41, p < 0.001) and enhanced the likelihood of achieving a target GC dose of ≤ 7.5 mg/day (OR 2.24, 95% CI 1.52–3.29, p < 0.001). In the pooled RWE cohorts (N = 294), the estimated attainment rate for LLDAS at 6–12 months was notably high at 75.8% (95% CI 68.4–82.5%). Additionally, 72.5% of real-world patients achieved a >50% reduction in GC dosage. Regarding safety, there was no significant increase in overall serious adverse events (OR 0.82, p = 0.25). Although anifrolumab was linked to a higher risk of HZ (OR 3.45, 95% CI 1.95–6.10, p < 0.001), both LTE and RWE data indicated that these cases were mainly mild to moderate and manageable. Conclusion: Anifrolumab offers rapid, strong, and sustained disease control while providing significant GC-sparing effects in both tightly controlled clinical trials and diverse real-world populations. The long-term safety profile remains stable; however, preventative measures, such as HZ vaccination, should be implemented as part of standard care.

Objective: To assess the efficacy and safety of Janus kinase inhibitors (JAKi) in patients with active systemic lupus erythematosus (SLE). Methods: We conducted a systematic review of randomized, double-blind, placebo-controlled phase 2 and 3 trials involving JAKi in adults with active SLE. Five trials (n=1802) were included, evaluating baricitinib 4 mg (n=3), deucravacitinib 3 mg twice daily (n=1), and upadacitinib 30 mg (n=1). The primary outcome was the SLE Responder Index-4 (SRI-4) response at weeks 24 to 52. Secondary outcomes included the BICLA response, Lupus Low Disease Activity State (LLDAS), and safety endpoints such as serious adverse events, serious infections, herpes zoster, and venous thromboembolism. Pooled odds ratios (ORs) were calculated using random-effects Mantel-Haenszel models. Results: JAKi significantly improved the SRI-4 response compared with placebo (54.4% vs. 43.8%; OR: 1.78, 95% CI: 1.41-2.25; p I ²=32%). Improvements were also observed in BICLA (OR: 1.92, 95% CI: 1.53-2.41) and LLDAS (OR: 2.01, 95% CI: 1.58-2.56). However, serious adverse events (OR: 1.48, 95% CI: 1.03-2.13) and serious infections (OR: 2.10, 95% CI: 1.21-3.65) occurred more frequently with JAKi, primarily driven by herpes zoster (OR: 3.24, 95% CI: 1.92-5.46). The rates of venous thromboembolism were comparable (OR: 1.13, 95% CI: 0.44-2.94). Conclusions: JAKi significantly improved disease activity across various composite endpoints in active SLE, demonstrating an acceptable safety profile characterized by an increased risk of herpes zoster but no evident signal for venous thromboembolism.

Introduction: The aim of the study was to systematically evaluate the efficacy, safety, immunogenicity, and pharmacokinetics (PK) of tocilizumab biosimilars compared to reference tocilizumab (r-TCZ) in patients with rheumatoid arthritis (RA) and healthy volunteers. Methods: We searched PubMed, Embase, and Cochrane CENTRAL for phase I and III randomized controlled trials (RCTs) comparing tocilizumab biosimilars vs. r-TCZ. Primary outcomes included change from baseline in DAS28-ESR, ACR20/50/70 response rates, adverse events (AEs), serious AEs (SAEs), anti-drug antibody (ADA) positivity, and PK parameters (AUC0−inf, Cmax, and AUC0−last). Random-effects meta-analyses were performed using mean difference (MD), risk ratio (RR), and geometric mean ratio (GMR) with 95% or 90% confidence intervals (CIs). This systematic review and meta-analysis have been registered in PROSPERO (CRD420251270353). Results: Eight studies met the inclusion criteria, comprising 3 phase III RCTs (n = 1,696 RA patients) and 5 phase I RCTs (n = 1,363 healthy volunteers), for a total of 3,059 participants. In RA patients, biosimilars demonstrated equivalent efficacy to r-TCZ at week 24, with no significant differences in DAS28-ESR change (MD −0.06; 95% CI: −0.19 to 0.06; I2 = 0%) or ACR20 response rates (RR 1.03; 95% CI: 0.96–1.10; I2 = 0). Results for ACR50 and ACR70 were similarly balanced. Safety profiles were comparable (any AE: RR 1.01; 95% CI: 0.94–1.08), as was immunogenicity (ADA positivity: RR 1.28; 95% CI: 0.99–1.65). In healthy volunteers, PK biosimilarity was confirmed across intravenous and subcutaneous routes with pooled GMRs (90% CI) of 104.5% (101.2–107.9%) for AUC0−inf, 101.4% (98.5–104.4%) for Cmax, and 102.3% (97.8–106.9%) for AUC0−last; all pooled CIs lay entirely within the 80–125% regulatory acceptance range (I2 ≤ 35). Conclusion: Tocilizumab biosimilars exhibit therapeutic similarity in RA patients and pharmacokinetic biosimilarity in healthy volunteers compared to r-TCZ, with comparable safety and immunogenicity, supporting their use as credible, cost-effective alternatives in clinical practice.