Purpose: This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non–small cell lung cancer (NSCLC). Materials and Methods: Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS). Results: In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment–related AEs occurred with lazertinib than gefitinib. Conclusion Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.

In this review, we will explore the intricate roles of cytokines and vascular endothelial growth factors in autoimmune diseases (ADs), with a particular focus on rheumatoid arthritis (RA) and multiple sclerosis (MS). AD is characterized by self-destructive immune responses due to auto-reactive T lymphocytes and Abs. Among various types of ADs, RA and MS possess inflammation as a central role but in different sites of the patients. Other common aspects among these two ADs are their chronicity and relapsing-remitting symptoms requiring continuous management. First factor inducing these ADs are cytokines, such as IL-6, TNF-α, and IL-17, which play significant roles in the pathogenesis by contributing to inflammation, immune cell activation, and tissue damage. Secondly, vascular endothelial growth factors, including VEGF and angiopoietins, are crucial in promoting angiogenesis and inflammation in these two ADs. Finally, placental growth factor (PlGF), an emerging factor with bi-directional roles in angiogenesis and T cell differentiation, as we introduce as an "angio-lymphokine" is another key factor in ADs. Thus, while angiogenesis recruits more inflammatory cells into the peripheral sites, cytokines secreted by effector cells play critical roles in the pathogenesis of ADs. Various therapeutic interventions targeting these soluble molecules have shown promise in managing autoimmune pathogenic conditions. However, delicate interplay between cytokines, angiogenic factors, and PlGF has more to be studied when considering their complementary role in actual pathogenic conditions. Understanding the complex interactions among these factors provides valuable insights for the development of innovative therapies for RA and MS, offering hope for improved patient outcomes.

Background/Aims: We aimed to clarify the clinical characteristics of psoriatic arthritis (PsA) in Korean patients focusing on PsA with axial involvement. Methods: A retrospective medical chart review was performed to identify PsA patients at a single tertiary center. Cases of AS patients with psoriasis were recruited from a prospective AS registry of the same center. Demographics, laboratory findings, and radiologic characteristics were assessed. Results: A total of 69 PsA patients were identified. In PsA patients, spondylitis (46.4%) was the most common form. Compared to AS patients with psoriasis, PsA patients with radiographic axial involvement were older (50.9 vs. 32.4 years; p < 0.001) and showed greater peripheral disease activity (peripheral arthritis 78.1 vs. 12.5%, p < 0.001; enthesitis 50.0 vs. 6.3%, p = 0.003). AS patients with psoriasis presented a higher rate of HLA-B*27 positivity (81.3 vs. 17.2%; p < 0.001) and a more frequent history of inflammatory back pain (100.0 vs. 75.0%; p = 0.039) than PsA patients with radiographic axial involvement. Significant proportions of PsA patients with radiographic axial involvement had cervical spine involvement (10/18, 55.6%) and spondylitis without sacroiliitis (10/23, 43.5%). Conclusions We demonstrate that axial involvement is common in Korean PsA patients, and its characteristics can be distinct from those of AS.

Background/Aims: Renal relapse has known to be a poor prognostic factor in patients with lupus nephritis (LN), but there were few studies that identified the risk factors of renal relapse in real world. We conducted this study based on 35-years of experience at a single center to find out predictors of renal relapse in Korean patients with LN after achieving complete response (CR). Methods: We retrospectively analyzed the clinical, laboratory, pathologic and therapeutic parameters in 296 patients of LN who reached CR. The cumulative risk and the independent risk factors for renal relapse were examined by Kaplan-Meier methods and Cox proportional hazards regression analyses, respectively. Results: The median follow-up period from CR was 123 months. Renal relapse had occurred in 157 patients. Renal relapse occurred in 38.2%, 57.6% and 67.9% of patients within 5-, 10-, and 20-year, respectively. The age at diagnosis of SLE and LN were significantly younger, and the proportions of severe proteinuria and serum hypoalbuminemia were higher in patients with renal relapse. Interestingly, the proportion of receiving cytotoxic maintenance treatment was higher in patients with renal relapse. In Cox proportional hazards regression analyses, only young-age onset of LN (by 10 years, HR = 0.779, p = 0.007) was identified to independent predictor of renal relapse. Conclusions Young-age onset of LN was only independent predictor and the patients with severe proteinuria and serum hypoalbuminemia also tended to relapse more, despite of sufficient maintenance treatment. Studies on more effective maintenance treatment regimens and duration are needed to reduce renal relapse.

Background/Aims: The aim of this study was to compare the short- and long-term retention rates of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) in Korean patients with seropositive rheumatoid arthritis. Methods: This study was conducted with 1,538 treatment courses of 1,063 patients, including adalimumab (n = 332), etanercept (n = 369), infliximab (n = 146), abatacept (n = 152), tocilizumab (n = 299), tofacitinib (n = 136), and baricitinib (n = 104), in patients with seropositive rheumatoid arthritis who started b/tsDMARD treatment between 2008 and 2020 at Seoul St. Mary’s Hospital. Discontinuation 1 and 3 years after the first prescription of each drug was investigated. Kaplan– Meier estimates of time to discontinuation were calculated to compare the difference in drug retention rate for each drug. Patient-level predictors of drug discontinuation were evaluated using a Cox proportional hazards model. Results: The overall 1-year drug retention rate was from 60.1% for adalimumab to 90.0% for tofacitinib in the b/tsDMARD-naïve group, and from 55.2% for infliximab to 84.8% for tofacitinib in the b/tsDMARD-experienced group. The 3-year drug retention rate was from 36.9% for infliximab to 86.5% for tofacitinib in the b/tsDMARD-naïve group, and from 31.0% for infliximab to 65.4% for tocilizumab in the b/tsDMARD-experienced group. Drug discontinuation appeared to be affected by specific types of b/tsDMARDs. Conclusions Tocilizumab and tofacitinib are less commonly discontinued compared to tumor necrosis factor-α inhibitors at 1 and 3 years. Specifically, tofacitinib in the b/tsDMARD-naïve group and tocilizumab in the b/tsDMARD-experienced group showed the highest 3-year retention rates.

Objective: To assess the effects of biological and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) on lipid profiles in patients with moderate-to-severe rheumatoid arthritis (RA). Methods: This retrospective single-center observational study included patients with RA taking a tumor necrosis factor-α inhibitor (TNFi), abatacept, tocilizumab, or a Janus kinase inhibitor (JAKi) for at least 6 months. Changes in lipid profile were assessed at 6 months after the start of treatment, and associations between changes in lipid profiles and clinical efficacy, concomitant medications, and comorbidities were evaluated. Results: This study included 114 patients treated with TNFi, 81 with abatacept, 103 with tocilizumab, and 89 with JAKi. The mean percentage change (from baseline to 6 months) in total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and non-HDL-C levels was higher in those taking tocilizumab and JAKi than in those taking TNFi and abatacept. A significant change in non-HDL-C was associated with JAKi (versus TNFi: odds ratio [OR], 3.228; 95% confidence interval [CI], 1.536~6.785), tocilizumab (versus TNFi: OR, 2.203; 95% CI, 1.035~4.689), and statins (OR, 0.487; 95% CI, 0.231~1.024). However, changes in disease activity in 28 joints were not associated with a significant change in non-HDL-C. Conclusion Tocilizumab- and JAKi-associated increases in serum non-HDL-C levels were observed regardless of changes in disease activity. Statins are recommended for RA patients showing a significant increase in cholesterol levels after initiating biological and targeted synthetic DMARDs.

Purpose: To evaluate the two-year longitudinal changes in subfoveal choroidal thickness (CT) following sulodexide treatment in patients with diabetic retinopathy. Methods: Thirty-eight eyes from patients with diabetic retinopathy, followed for a minimum of two years after sulodexide administration, were included. Subfoveal CT, measured using optical coherence tomography, was analyzed prospectively. Variables including age, sex, duration of diabetes mellitus, HbA1c, blood pressure, sulodexide treatment duration, refractive error, axial length, central macular thickness (CMT), visual acuity, laser photocoagulation, and intravitreal anti-vascular endothelial growth factor injections were evaluated for potential effects on CT. CMT, subfoveal CT, and choroidal vascularity index were compared at baseline and at 6, 12, and 24 months after sulodexide. Results: Of the 38 eyes, 10 belonged to males and 28 to females. The mean data were as follows: age, 67.18 ± 8.87 years; duration of diabetes, 18.11 ± 7.57 years; HbA1c, 8.76 ± 1.60 mmol/L; systolic blood pressure, 134.69 ± 14.68 mmHg; diastolic blood pressure, 73.72 ± 11.90 mmHg; duration of sulodexide, 25.79 ± 3.17 months; refractive error, 0.22 ± 2.19 diopters (D); and axial length, 23.32 ± 0.89 mm. During the observation period, 15 eyes underwent laser photocoagulation and 17 eyes received intravitreal anti-vascular endothelial growth factor injections. The mean subfoveal CT was 216.00 ± 64.23 μm before sulodexide administration and increased to 223.87 ± 62.18 μm, 225.53 ± 62.02 μm, and 225.76 ± 63.62 μm at 6, 12, and 24 months, respectively (p = 0.0377, p = 0.0159, p = 0.0135). The CMT was 318.14 ± 102.28 μm initially and changed to 313.08 ± 77.47 μm, 314.97 ± 88.32 μm, and 320.03 ± 97.36 μm at the aforementioned intervals, with no significant variation (p = 0.904, p = 0.736, p = 0.892). Conclusions Sulodexide administration led to a significant rise in subfoveal CT over a 2-year follow-up. This change in CT was not mirrored in the CMT.

Objective: With many chronic inflammatory diseases, outcomes are determined by assessing both disease activity at presentation and cumulative activity over time. Here, we investigated whether cumulative activity better reflects the radiographic progression (RP) of rheumatoid arthritis (RA) than measurement of activity at a single time point. Methods: From a prospective cohort of RA patients, most of whom were treated with anti-rheumatic drugs, we selected 117 subjects for whom laboratory, clinical, and radiographic parameters potentially influencing RP were monitored serially for more than 1 year. X-ray images of both hands and both feet were scored using the van der Heijde modified total Sharp score (mTSS). In addition to cross-sectional values at baseline, longitudinal and cumulative values for each parameter were calculated in a timeintegrated and averaged manner. Results: Among the values measured at baseline, mTSS, but not the baseline erythrocyte sedimentation rate (ESR) or C-reactive protein level, was associated with RP. By contrast, multivariate analyses identified cumulative values such as the cumulative ESR, cumulative tender joint count, cumulative swollen joint count (SJC), and cumulative Disease Activity Score 28-ESR as major determinants of RP. In particular, the cumulative SJC showed the best predictive performance for RP. Conclusion This study highlights the importance of cumulative indices for predicting progression of RA. Specifically, dynamic and cumulative values of RA activity-related factors, particularly the cumulative SJC, may be the major determinants of RP in the current practice.

In the past few decades, biological drugs and small molecule inhibitors targeting inflammatory cytokines, immune cells, and intracellular kinases have become the standard-of-care to treat autoimmune diseases. Inhibition of TNF, IL-6, IL-17, and IL-23 has revolutionized the treatment of autoimmune diseases, such as rheumatoid arthritis, ankylosing spondylitis, and psoriasis. B cell depletion therapy using anti-CD20 mAbs has shown promising results in patients with neuroinflammatory diseases, and inhibition of B cell survival factors is approved for treatment of systemic lupus erythematosus. Targeting co-stimulatory molecules expressed on Ag-presenting cells and T cells is also expected to have therapeutic potential in autoimmune diseases by modulating T cell function. Recently, small molecule kinase inhibitors targeting the JAK family, which is responsible for signal transduction from multiple receptors, have garnered great interest in the field of autoimmune and hematologic diseases. However, there are still unmet medical needs in terms of therapeutic efficacy and safety profiles. Emerging therapies aim to induce immune tolerance without compromising immune function, using advanced molecular engineering techniques.