Comparative risk of serious infections and tuberculosis in Korean patients with inflammatory bowel disease treated with non-anti-TNF biologics or anti-TNF-α agents: a nationwide population-based cohort study.

Background: The risk of serious infection and active tuberculosis in patients with inflammatory bowel disease (IBD) has not been concurrently evaluated based on the use of anti-tumor necrosis factor (TNF)-α agents versus non-anti-TNF biologics (vedolizumab/ustekinumab) in the Korean population. Objectives: We compared the risk of serious infection and active tuberculosis in Korean patients with IBD treated with non-anti-TNF biologics (vedolizumab/ustekinumab) or anti-TNF-α agents. Design: This study was a population-based cohort analysis of nationwide administrative claims data. Methods: Health Insurance Review and Assessment Service claims data (representing 97% of the South Korean population) from between January 2007 and February 2021 were reviewed, and adults with IBD who initiated vedolizumab/ustekinumab or anti-TNF-α treatment (n = 6123) between 2017 and 2020 were enrolled. Intergroup differences in the risk of serious infection requiring hospitalization/emergency department visits or active tuberculosis during the follow-up period were analyzed. Results: In the patients treated with anti-TNF-α agents or vedolizumab/ustekinumab during a mean follow-up of 1.55 ± 1.05 and 0.84 ± 0.69 years, the incidence rates of serious infection were 9.43/100 and 6.87/100 person-years, respectively. Multivariable analysis showed no significant intergroup difference in the risk of serious infection with vedolizumab/ustekinumab or anti-TNF-α treatment; the adjusted relative risk of vedolizumab/ustekinumab compared with anti-TNF-α agents was 0.81 (95% confidence interval 0.46-1.44, p = 0.478). Among patients treated with anti-TNF-α agents and vedolizumab/ustekinumab, the incidence rates of active tuberculosis were 0.87 and 0.37 per 100 person-years, respectively. The relative risk of vedolizumab/ustekinumab compared with anti-TNF-α agents was 0.31 (95% confidence interval 0.07-1.26, p = 0.101). In a subset analysis comparing vedolizumab and ustekinumab with anti-TNF-α agents, similar results were observed. Conclusion: In Korean patients with IBD, non-anti-TNF biologics (vedolizumab/ustekinumab) tended to be associated with a lower risk of serious infection or active tuberculosis than anti-TNF-α agents.

Expression of CD163 and major histocompatibility complex class I as diagnostic markers for idiopathic inflammatory myopathies.

BACKGROUND: To develop an inflammation-related immunohistochemistry marker-based algorithm that confers higher diagnostic ability for idiopathic inflammatory myopathies (IIMs) than IIM-related histopathologic features. METHODS: Muscle biopsy tissues from 129 IIM patients who met the 2017 EULAR/ACR criteria and 73 control tissues from patients with non-inflammatory myopathies or healthy muscle specimens were evaluated for histological features and immunostaining results of CD3, CD4, CD8, CD20, CD68, CD163, MX1, MHC class I, MHC class II, and HLA-DR. Diagnostic algorithms for IIM were developed based on the results of the classification and regression tree (CART) analysis, which used immunostaining results as predictor variables for classifying patients with IIMs. RESULTS: In the analysis set (IIM, n = 129; control, n = 73), IIM-related histopathologic features had a diagnostic accuracy of 87.6% (sensitivity 80.6%; specificity 100.0%) for IIMs. Notably, muscular expression of CD163 (99.2% vs. 20.8%, p < 0.001) and MHC class I (87.6% vs. 23.1%, p < 0.001) was significantly higher in the IIM group than in controls. Based on the CART analysis results, we developed an algorithm combining CD163 and MHC class I expression that conferred a diagnostic accuracy of 95.5% (sensitivity 96.1%; specificity 94.5%). In addition, our algorithm was able to correctly diagnose IIM in 94.1% (16/17) of patients who did not meet the 2017 EUALR/ACR criteria but were diagnosed as having IIMs by an expert physician. CONCLUSIONS: Combination of CD163 and MHC class I muscular expression may be useful in diagnosing IIMs.

Prognostic factors for chronic thrombocytopenia in systemic lupus erythematosus with immune thrombocytopenia.

INTRODUCTION: We aimed to identify the clinical characteristics and risk factors for chronic immune thrombocytopenia (ITP) in patients with systemic lupus erythematosus (SLE). METHODS: We retrospectively reviewed patients diagnosed with SLE-associated ITP between January 2000 and December 2021. Patient characteristics were analyzed according to the progression of chronic thrombocytopenia. No response was defined as a platelet count < 30 ×109/L or less than double the baseline count after treatment. Factors associated with chronic ITP were evaluated by logistic regression analysis. RESULTS: Among the 121 patients with SLE-associated ITP, 27 progressed to chronic ITP lasting more than one year after initial diagnosis. The median initial platelet count was significantly lower in patients with chronic thrombocytopenia than in those without the disease (16 vs. 51 × 109/L). Patients who did not achieve a response within one month of treatment exhibited a high probability of progressing to chronic ITP (55.6% vs. 22.3%, p <0.001). Multivariable analysis revealed that severe thrombocytopenia at baseline (<20 × 109/L) (adjusted odds ratio [aOR] = 13.628, 95% confidence interval [CI] = 3.976-46.791) and no response within one month (aOR=9.171, 95% CI=2.776-30.298) were significantly associated with the risk of progression to chronic ITP in patients with SLE. Approximately one-quarter of the patients with SLE-associated ITP progressed to chronic ITP. CONCLUSION: Severe thrombocytopenia, and failure to achieve a response within one month were risk factors for the development of chronic ITP in those patients.

Progression to ANCA-associated vasculitis in patients with idiopathic interstitial pneumonia and positive ANCA.

OBJECTIVE: This study explored the development of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and its risk factors in patients with idiopathic interstitial pneumonia (IIP) and positive ANCA results. METHODS: Data of patients diagnosed with IIP with positive ANCA results at a single tertiary center in South Korea were retrospectively reviewed from January 2013 to August 2023. Cox regression analysis was performed to identify variables associated with AAV occurrence following IIP diagnosis. Kaplan-Meier curves were employed to investigate the relationship between autoantibodies and the occurrence of AAV. RESULTS: In a cohort of 154 IIP-diagnosed patients with positive ANCA results but without AAV, 10.4 % of them eventually developed AAV. The AAV and non-AAV groups did not significantly differ by sex, age, smoking status, urinalysis, or chest computed tomography findings. All the patients who subsequently developed AAV were anti-myeloperoxidase (MPO) positive, while 48.8 % of the non-AAV patients were anti-MPO positive (P < 0.001). Rheumatoid factor (RF) positivity differed significantly (62.5 % vs. 29.2 %, P = 0.007) between the AAV and non-AAV groups. Multivariate Cox regression and Kaplan-Meier analyses revealed RF (HR 4.02; P = 0.004) and anti-MPO (HR 38.10; P < 0.001) positivity as risk factors associated with AAV occurrence. CONCLUSION: Approximately 10 % of ANCA-positive IIP patients developed AAV after an IIP diagnosis. Anti-MPO or co-occurring positive RF poses a significant risk for subsequent AAV occurrence. This emphasizes the importance of careful monitoring in patients with high-risk antibody profiles, even if the complete features of AAV are not present at IIP diagnosis.

Drug survival and change of disease activity using a second janus kinase inhibitor in patients with difficult-to-treat rheumatoid arthritis who failed to a janus kinase inhibitor and subsequent biologics.

BACKGROUND: To assess the drug survival and change of disease activity using a second Janus kinase inhibitor (JAKi) after failure to a JAKi and subsequent biologic disease-modifying anti-rheumatic drugs (bDMARDs) in patients with difficult-to-treat rheumatoid arthritis (RA). METHODS: This retrospective cohort study included 32 patients with difficult-to-treat RA who failed to a JAKi and subsequently to one or more bDMARDs and then switched to a second JAKi. To assess drug survival, electronic medical records of each patient were reviewed. Data on whether the second JAKi was discontinued, and the reasons for discontinuation were collected. The change of disease activity was assessed by analyzing changes in tender joint count (TJC), swollen joint count (SJC), patient's global assessment of disease activity on a visual-analogue scale (VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Disease Activity Score for 28 joints with ESR (DAS28-ESR), and DAS28-CRP from baseline to that at six months from initiation of the second JAKi. RESULTS: Overall, discontinuation of the second JAKi occurred in 20 (62.5%) patients. Primary failure, secondary failure, adverse events, and insurance coverage issues were the reasons for discontinuation in 9 (45.0%), 5 (25.0%), 2 (10.0%), and 4 (20.0%) patients, respectively. The estimated 2-year drug survival rate was 39.3%. In terms of change of disease activity, the second JAKi significantly improved TJC (p < 0.001), SJC (p < 0.001), VAS (p < 0.001), CRP (p = 0.026), DAS28-ESR (p < 0.001), and DAS28-CRP (p < 0.001) at 6-month compared with that at the baseline. CONCLUSIONS: Second JAKi could be a therapeutic option in patients with difficult-to-treat RA who have failed to a JAKi and subsequent bDMARDs.

Continued JAK inhibitor treatment on the risk of recurrent herpes zoster reactivation in patients with immune-mediated inflammatory diseases: A nationwide population-based study in South Korea.

BACKGROUND: To investigate the risk of recurrent herpes zoster (HZ) reactivation under continued Janus kinase inhibitor (JAKi) therapy in patients with immune-mediated inflammatory diseases (IMID) who developed HZ reactivation. METHODS: Data from the Korean Health Insurance Review and Assessment Service (HIRA) of patients with rheumatoid arthritis (RA) or ulcerative colitis (UC) gathered from 2007 to 2021 were analyzed. RESULTS: A total of 3947 (RA 3540, UC 407) receiving JAKi were included. After median 0.95 years (IQR, 0.93-2.58) of therapy, 611 (15.5%) patients developed HZ reactivation (incidence rate: 8.38/100 person-years [PY]). After excluding 151 patients with lack of data after HZ reactivation, 460 patients (JAKi continuation group, n = 386 [83.9%]; JAKi discontinuation group, n = 74 [16.1%]) were analyzed for the risk of subsequent recurrent HZ reactivation. During further follow-up of median 1.11 years (IQR, 0.53-1.91), 36 (9.3%) and 6 (8.1%) patients in the JAKi continuation group and JAKi discontinuation group experienced a recurrence of HZ, respectively. The incidence rate of subsequent recurrent HZ reactivation was not significantly different between the two groups (5.3/100 vs. 5.9/100 PY; P = 0.52). After adjusting for age, sex, usage of corticosteroids, and antiviral agents, continued use of JAKi was not a significant risk factor for subsequent HZ reactivation (adjusted hazard ratio, 0.71 [CI, 0.29-1.72], P = 0.45). CONCLUSION: In this nationwide population-based study on patients with RA or UC, continued use of JAKi was not associated with a significant risk of subsequent recurrent HZ reactivation. JAKi therapy may be maintained in patients with IMID even after HZ reactivation.

Effect of belimumab in patients with systemic lupus erythematosus treated with low dose or no corticosteroids.

BACKGROUND/AIMS: Systemic lupus erythematosus (SLE) responder index (SRI)-4 response has been achieved with belimumab treatment in patients with moderate disease activity in cornerstone clinical trials and following studies. However, most studies involved patients treated with a mean prednisolone-equivalent dose of approximately 10 mg/d and focused on the steroid-sparing effect of belimumab. We aimed to identify the effect of belimumab in patients with mild-to-moderate SLE who were treated with low-dose or no corticosteroids. METHODS: We retrospectively reviewed the electronic medical records of patients treated with belimumab for at least 6 months between May 2021 and June 2022. The primary endpoint was SRI-4 response at 6 months. RESULTS: Thirty-one patients were included (13 low dose- and 18 steroid non-users). The mean age was 39.2 ± 11.4 years, and 90.3% of patients were female. The baseline Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score was 6.0 (4.0-9.0). The primary endpoint was achieved in 32.3% (10/31) of patients. Significant improvements in anemia, C4 levels, and SELENA-SLEDAI score were observed during treatment. Univariate analysis showed that the baseline SELENA-SLEDAI and arthritis were significantly associated with SRI-4 response at 6 months, and only the SELENA-SLEDAI remained significant (p = 0.014) in multivariate analysis. CONCLUSION: This cohort study is the first to report the efficacy of belimumab after minimizing the effect of corticosteroids. Belimumab showed efficacy in improving the SELENA-SLEDAI score, anemia, and low C4 in patients who did not receive corticosteroids or received only low doses.

Febuxostat dose requirement according to renal function in patients who achieve target serum urate levels: A retrospective cohort study.

OBJECTIVES: To determine the febuxostat dose requirement according to renal function in patients who achieve target serum urate (SU) levels. METHODS: Of 3153 gout patients who underwent febuxostat treatment, 873 patients with an initial SU level>6mg/dL were included and categorized by the estimated glomerular filtration rate: normal, chronic kidney disease (CKD) stage 3, and stages 4-5. Ninety-five patients with insufficient follow-up were further excluded. The dose of febuxostat in patients who achieved the SU target (< 6mg/dL) was defined as the average daily dosage at the time of SU target achievement. RESULTS: The cohort of 778 gout patients had a median age of 52.0 years (IQR, 41.0-63.0) and comprised 711 (91.4%) men. The mean SU at febuxostat initiation was higher in the CKD 4-5 (9.6 [± 3.1] mg/dL) than in the other groups (CKD 3, 8.7 [± 1.7]; normal, 8.4 [± 1.7]; P<0.001). Patients achieved target SU at a median of 4.0 (1.9-9.6) months and in those who achieved target SU, the dose of febuxostat at the time of SU target achievement was significantly lower in the CKD 4-5 group (50.0 [± 16.5] mg) than in the other groups (vs. CKD stage 3, 60.0 [± 19.5] mg; P<0.01, vs. normal, 60.0 [± 19.8] mg; P<0.01). Furthermore, CKD stage 4-5 had a negative correlation with the febuxostat dose requirement (Beta: -2.334, P<0.05). CONCLUSION: Among patients who achieved SU target, those with severely decreased renal function (CKD 4-5) required a lower febuxostat dose to achieve the target SU level compared to patients with normal or mild renal impairment.

Relapse in patients with antineutrophil cytoplasmic antibody-associated vasculitis undergoing dialysis: a single-centre retrospective study in South Korea.

OBJECTIVES: The disease activity of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) can decrease after dialysis, and relapse after dialysis is not well-studied. We investigated the clinical manifestations and factors associated with relapse in patients with AAV undergoing dialysis. METHODS: This retrospective study included data of patients with AAV undergoing dialysis due to renal involvement from July 2005 to March 2021 in a single tertiary centre in Seoul, Korea. Cox regression analysis was performed to identify relapse-associated factors. RESULTS: The study cohort included 38 patients with a median age of 64.0 years; 28 (73.7%) were female, and 35 (92.1%) patients were diagnosed with microscopic polyangiitis (MPA). At diagnosis, the mean Birmingham vasculitis activity score (BVAS) was 18.3 and 66.3% of the patients exhibited pulmonary manifestations. During follow-up, 12 patients experienced AAV relapse, including nine patients with diffuse alveolar haemorrhage (DAH), two patients with aggravated interstitial lung disease, and one patient with DAH accompanied with neuropathy. Clinical features including age, sex, and baseline BVAS did not significantly differ between the relapse and non-relapse groups. By univariable analysis, lung infiltration, DAH, corticosteroid pulse therapy for induction, and mean corticosteroid dose were significantly associated with relapse. Multivariable analysis revealed that DAH (adjusted hazard ratio 5.509, 95% CI 1.569-19.339; P=0.008) and mean corticosteroid dose (adjusted hazard ratio 1.381, 95% CI 1.161-1.642; P<0.001) were significantly associated with relapse. CONCLUSIONS: In patients with AAV undergoing dialysis, DAH and mean corticosteroid dose were significantly associated with relapse, highlighting the importance of close monitoring.

Drug survival and change of disease activity using a second janus kinase inhibitor in patients with difficult-to-treat rheumatoid arthritis who failed to a janus kinase inhibitor and subsequent biologics

Abstract Background To assess the drug survival and change of disease activity using a second Janus kinase inhibitor (JAKi) after failure to a JAKi and subsequent biologic disease-modifying anti-rheumatic drugs (bDMARDs) in patients with difficult-to-treat rheumatoid arthritis (RA). Methods This retrospective cohort study included 32 patients with difficult-to-treat RA who failed to a JAKi and subsequently to one or more bDMARDs and then switched to a second JAKi. To assess drug survival, electronic medical records of each patient were reviewed. Data on whether the second JAKi was discontinued, and the reasons for discontinuation were collected. The change of disease activity was assessed by analyzing changes in tender joint count (TJC), swollen joint count (SJC), patient's global assessment of disease activity on a visual-analogue scale (VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Disease Activity Score for 28 joints with ESR (DAS28-ESR), and DAS28-CRP from baseline to that at six months from initiation of the second JAKi. Results Overall, discontinuation of the second JAKi occurred in 20 (62.5%) patients. Primary failure, secondary failure, adverse events, and insurance coverage issues were the reasons for discontinuation in 9 (45.0%), 5 (25.0%), 2 (10.0%), and 4 (20.0%) patients, respectively. The estimated 2-year drug survival rate was 39.3%. In terms of change of disease activity, the second JAKi significantly improved TJC (p < 0.001), SJC (p < 0.001), VAS (p < 0.001), CRP (p = 0.026), DAS28-ESR (p < 0.001), and DAS28-CRP (p < 0.001) at 6-month compared with that at the baseline. Conclusions Second JAKi could be a therapeutic option in patients with difficult-to-treat RA who have failed to a JAKi and subsequent bDMARDs.

Clinical features of systemic lupus erythematosus patients with splenomegaly: focussed on the cytopenias.

This study aimed to investigate the clinical features of splenomegaly, mainly focussing on cytopenia, in patients with systemic lupus erythematosus (SLE). Cytopenia was commonly observed in 111 SLE patients with splenomegaly (n = 79, 71.2%). During the follow-up period, two patients developed haematologic malignancy after the diagnosis of SLE and splenomegaly, but no patients experienced severe complications (e.g. splenic rupture) related to splenomegaly.

The Expression of the Alpha7 Nicotinic Acetylcholine Receptor and the Effect of Smoking in Curdlan-Administered SKG Mice.

Nicotine, an abundant molecule in tobacco, has immunomodulatory effects on inflammatory diseases, primarily due to the activation of alpha7 nicotinic acetylcholine receptor (α7 nAChR). We aim to evaluate the expression of the α7 nAChR+ cells in joint tissue and the effect of smoking on immune cells and peripheral arthritis in curdlan-administered SKG mice, a murine model of spondyloarthropathy (SpA). The SKG mice were injected with curdlan two times at 2-week intervals and were divided into two groups; one exposed to cigarette smoke and the other not exposed. We found that the α7 nAChR+ cells increased in the joint tissue of curdlan-administered SKG mice compared to in the wild type. Furthermore, the peripheral arthritis scores and histological scores for synovial inflammation were lower in smoke-exposed curdlan-administered SKG mice than in mice not exposed to smoke. Immunofluorescence staining of the α7 nAChR+ and IL-17A+ cells was lower in the synovia of smoke-exposed mice than the control mice. The proportions of α7 nAChR+IL-17A+ and α7 nAChR+IL-17A+FOXP3+ cells also decreased in the synovia of smoke-exposed mice compared with the controls. We observed an increase in the α7 nAChR+ cells within the joint tissue of curdlan-administered SKG mice and that cigarette smoke had an influence on both peripheral arthritis and immune cell population, especially α7 nAChR+ cells. Thus, exposure to cigarette smoke after arthritogenic stimuli may have an anti-arthritogenic effect in curdlan-administered SKG mice.

Clinical effect of progressive pulmonary fibrosis on patients with connective tissue disease-associated interstitial lung disease: a single center retrospective cohort study.

The concept of progressive pulmonary fibrosis (PPF) has been introduced to predict the diverse prognosis of interstitial lung disease (ILD). However, the incidence and effect of PPF on outcomes in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD) need to be elucidated. This study reviewed 197 patients with CTD-ILD. Symptomatic worsening, pulmonary function decline, and radiological deterioration were investigated to assess the fulfillment of PPF diagnostic criteria. Clinical outcomes, including mortality, were compared based on the presence or absence of PPF. The median follow-up duration was 17.4 months. The mean age of the patients was 64.0 years, and 60.9% were female. Among the underlying CTDs, rheumatoid arthritis (42.1%), inflammatory myositis (19.8%), and systemic sclerosis (13.2%) were the most common. Of the 197 patients, 37 (18.8%) met the diagnostic criteria for PPF during the follow-up period. Even after adjusting for other significant risk factors, PPF was independently associated with mortality [hazard ratio (HR) 3.856; 95% confidence interval (CI) 1.387-10.715; P = 0.010] and baseline albumin was marginally significantly associated with mortality (HR 0.549; CI 0.298-1.010; P = 0.054). The median survival was also significantly shorter in the PPF group than in the non-PPF group (72.3 ± 12.9 vs. 126.8 ± 15.5 months, P < 0.001). Baseline KL-6 ≥ 1000 (U/mL) was a significant risk factor for PPF (HR 2.885; CI 1.165-7.144; P = 0.022). In addition to increased mortality, the PPF group had significantly higher rates of respiratory-related hospitalizations, pneumonia, acute exacerbations, and weight loss than the non-PPF group. PPF is a significant prognostic indicator in patients with CTD-ILD. Thus, healthcare professionals should know that patients with CTD-ILD are at risk of PPF.

When MRI would be useful in patients without evidence of sacroiliitis on radiographs?

We aimed to identify when magnetic resonance imaging (MRI) would be useful to diagnose patients with suspected axial spondyloarthropathy (AxSpA) without evidence of sacroiliitis on radiographs. We retrospectively reviewed electronic medical records of patients who underwent pelvis MRI after radiographs at the rheumatology clinic in a single tertiary center in Korea. Patients underwent imaging from January 2020 to July 2022. We collected data including complete blood count, erythrocyte sedimentation rate, C-reactive protein (CRP), human leukocyte antigen (HLA)-B27, history of acute anterior uveitis (AAU), peripheral arthritis, dactylitis, inflammatory bowel disease (IBD), enthesopathy, and psoriasis. A total of 105 patients who showed no evidence of sacroiliitis on radiographs were included. The median age of patients was 41.0 years, and 44.8% were male. Of them, 34 showed sacroiliitis on MRI (group 1), and 71 showed no evidence of sacroiliitis even on MRI (group 2). Known AxSpA-related clinical features including AAU, peripheral arthritis, dactylitis, IBD, enthesopathy, and psoriasis were not different between the two groups. HLA-B27 positivity (79.4% vs. 40.0%, p < 0.001), median white blood cell count (7700 vs. 6300, p = 0.007), mean platelet count (307.7 ± 69.7 vs. 265.3 ± 68.9 × 103/µL, p = 0.005), and median CRP level (0.38 vs. 0.10, p = 0.001) showed significant differences between the two groups. In a multivariate analysis, HLA-B27 positivity and platelet count were significantly associated with sacroiliitis on MRI. In our cohort, sacroiliitis was observed on MRI in one-third of patients without radiographic evidence. MRI could be recommended to evaluate sacroiliitis in patients with positive HLA-B27 and a high platelet count.

Recovery and long-term renal outcome of patients with anti-neutrophil cytoplasmic antibody-associated vasculitis who are on dialysis at presentation.

Objective: Renal involvement in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) can lead to severe renal dysfunction requiring dialysis at diagnosis. We aimed to study the clinical and pathologic characteristics of patients with AAV dependent on dialysis at presentation and the long-term renal outcomes of patients who recovered from dialysis. Methods: This retrospective study analyzed data of patients diagnosed with AAV who were on dialysis from July 2005 to May 2021 at a single tertiary center in Korea. Results: Thirty-four patients were included in the study (median age 64.5 years, females 61.8%), of which 13 discontinued and 21 continued dialysis. The proportion of normal glomeruli (p<0.001) and interstitial fibrosis (p=0.024) showed significant differences between both groups. Multivariable analysis showed that the proportion of normal glomeruli was associated with dialysis discontinuation (odds ratio=1.29, 95% confidence interval 0.99~1.68, p=0.063), although without statistical significance. Treatment modalities, including plasmapheresis, did not show significance with dialysis discontinuation. In the follow-up analysis of 13 patients who had discontinued dialysis for a median of 81 months, 12 did not require dialysis, and their glomerular filtration rate values significantly increased at follow-up time compared to when they stopped dialysis (37.5 [28.5~45.5] vs. 24.0 [18.5~30.0] mL/min/1.73 m²; p=0.008). Conclusion: Approximately 38% of AAV patients on dialysis discontinued dialysis, and the recovered patients had improved renal function without dialysis during longer follow-up. Patients with AAV on dialysis should be given the possibility of dialysis discontinuation and renal recovery, especially those with normal glomeruli in kidney pathology.

Urine SERPINC1/ORM1 as biomarkers for early detection of lupus nephritis in MRL-lpr mice.

Background: To evaluate the usefulness of urine SERPINC1 and ORM1 as biomarkers for early detection of lupus nephritis (LN). Methods: Using proteomics, we screened for potential urine biomarkers that differentiate LN from systemic lupus erythematosus (SLE) patients without nephritis. In addition, urine levels of target biomarkers were measured by ELISA in 13- and 23-week-old MRL-lpr (murine model for LN) and MRL/MpJ mice. Histological analysis was also performed on the kidneys of 23-week-old mice. Results: Urine SERPINC1 and ORM1 were elevated in SLE patients with newly diagnosed LN compared with SLE patients without LN (SERPINC1, AUC=.892, P<.001; ORM1, AUC=.886, P<.001). Levels of urine SERPINC1 and ORM1 were also significantly higher in MRL-lpr mice than in MRL/MpJ mice at 13 and 23 weeks (SERPINC1: p<.01 and p<.001 at 13 and 23 weeks, respectively; ORM1: p<.01 at 13 and 23 weeks). In contrast, a significant difference in urine albumin between the two groups was only observed at 23 weeks (p<.001) not at 13 weeks (p=.83). Regarding the kidney pathology of MPL-lpr mice, urine ORM1 and urine albumin, but not urine SERPINC1, were positively correlated with the activity index (ORM1, rho =.879, p<.001; albumin, rho =.807, p=.003) and chronicity index (ORM1, rho =.947, p<.001; albumin, rho =.869, p<.001). Conclusion: We propose that urine SERPINC1 and ORM1 are novel biomarkers for early LN.

Long-term renal outcomes of patients with non-proliferative lupus nephritis.

BACKGROUND/AIMS: Although non-proliferative lupus nephritis (LN) (class I, II or V) has been considered as a less severe type of LN, data on long-term renal prognosis are limited. We investigated the long-term outcomes and prognostic factors in non-proliferative LN. METHODS: We retrospectively reviewed patients with systemic lupus erythematosus who were diagnosed with LN class I, II, V, or II + V by kidney biopsy from 1997 to 2021. A poor renal outcome was defined as an estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m2. RESULTS: We included 71 patients with non-proliferative LN (class I = 4; class II = 17; class V = 48; class II+V = 2), and the overall rate of poor renal outcomes was 29.6% (21/71). The univariate analysis indicated that older age, low eGFR at 6 or 12 months, failure to reach complete remission at 6 months, and LN chronicity score > 4 or activity score > 6 were significantly associated with poor renal outcomes. The multivariate analysis revealed that low eGFR at 6 months (HR 0.971, 95% CI 0.949-0.991; p = 0.014) was significantly associated with poor renal outcomes. CONCLUSION: Poor renal outcomes occurred in approximately 30% of patients with non-proliferative LN after long-term follow-up. More active management may be needed for non-proliferative LN, especially for patients with eGFR < 60 mL/ min/1.73 m2 at 6 months follow-up after LN diagnosis.

Incidence of and risk factors for myelodysplastic syndromes in patients with rheumatologic diseases.

OBJECTIVE: We investigated the incidence rate and risk factors of myelodysplastic syndromes (MDS) in patients with rheumatologic disease. METHODS: We conducted a retrospective cohort study of patients who were diagnosed with rheumatologic diseases at a tertiary-care hospital between May 2009 and July 2022 and identified the patients who were subsequently diagnosed with MDS. Each patient with MDS was matched with five age- and sex-matched controls chosen from the cohort of patients with each specific rheumatologic disease. RESULTS: During a total follow-up of 55 841 person-years (PY), MDS occurred in 64 patients, yielding an incidence rate of 1.15/1000 PY (median age, 57.0 [IQR, 41.0-69.0]; median duration to MDS diagnosis, 6.5 years [IQR, 3.0-9.0]). In an age-matched analysis, systemic lupus erythematosus (SLE) was a significant risk factor for MDS (adjusted hazard ratio, 2.61 [CI, 1.19-36.06], P= 0.01). Refractory cytopenia with multilineage dysplasia was the most common phenotype of MDS (35.9%), and more than half of the patients had karyotypes with favorable prognoses (54.7%). Compared with matched controls, rheumatoid arthritis, SLE, and ankylosing spondylitis patients with MDS had lower levels of haemoglobin at the time of diagnosis of rheumatologic disease. Furthermore, the MDS patients with SLE and Behcet's disease had higher levels of glucocorticoid use in terms of frequency of use or mean dose than the control patients. CONCLUSION: SLE is a significant risk factor for MDS among patients with rheumatologic diseases. A lower haemoglobin level at the time of diagnosis of rheumatologic disease was associated with the future development of MDS.

Association of citrullination with the progression of aortic stenosis.

Despite its clinical importance, biomarkers of disease activity in aortic stenosis (AS) are lacking. We investigated the association between anti-cyclic citrullinated peptide (CCP) antibodies and AS. All 678 patients who underwent echocardiography and anti-CCP antibody testing were analysed. Anti-CCP antibody status was categorized as negative, low-positive, and high-positive. In addition, aortic valve (AV) tissues were obtained from the patients with and without AS to analyze the presence of citrullinated proteins. At baseline, 241 (35.5%) subjects with AV degeneration had a higher rate of anti-CCP antibody positivity (42.7% versus 34.6%, p = 0.035) than those without AV degeneration. Out of the 331 (48.8%) subjects who underwent echocardiographic follow-up, progression of AS was observed in 34 (10.3%) patients, with a higher incidence in the high-positive group compared to the low-positive or negative group (19.0% vs. 11.3% vs. 8.4%, respectively; p = 0.041). On multivariable analysis, high anti-CCP antibody positivity was independently associated with progression to AS (odds ratio: 2.312; 95% confidence interval: 1.006-5.310; p = 0.048). Furthermore, immunohistochemistry and Western blotting revealed increased citrullination in diseased AV compared to normal AV tissue. This study demonstrated that a high positive anti-CCP antibody result is associated with AV degeneration and may be an independent factor for AS progression.

Anti-S1/RBD-Specific Antibody Formation After SARS-CoV-2 Vaccination in Elderly Rheumatoid Arthritis Patients: Single-Center Prospective Observational Study.

BACKGROUND: The guidelines of coronavirus disease 2019 (COVID-19) vaccination in patients with rheumatoid arthritis (RA) have been continuously updated, with extensive discussion on the effectiveness of the COVID-19 booster vaccines and antibody generation associated with the different types of vaccine. We investigated the effects of the third dose of the mRNA vaccine on antibody titer and the factors associated with antibody production in patients with RA who had previously received two doses of the ChAdOx1-S nCoV-19 vaccine. METHODS: Between October 14, 2021 and June 17, 2022, two patient groups diagnosed with RA were recruited prospectively: one with two doses of ChAdOx1-S nCoV-19 and the second group with the additional third mRNA vaccine. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody titers were determined through semiquantitative anti-SARS-CoV-2 spike (S) electrochemiluminescence immunoassay. Antibody titers were compared in both groups considering clinical features and medications. Multivariate logistic regression was performed to identify the factors associated with antibody production. Also, we followed up the antibody titers of whom completed the 3rd mRNA vaccination. RESULTS: Among 261 patients, all patients were over 60 years old except for 7 patients and the average age was 65 years; 153 had completed two doses of ChAdOx1-S nCoV-19, while 108 patients had also received the third mRNA vaccine. The positive rates of anti-SARS-CoV-2 anti-S1/receptor binding domain-specific antibody (titer > 0.8 U/mL) were 97% (149/153) and 99% (107/108) respectively. However, positive rates for high antibody titer (> 250 U/mL) were found in only 31% (47/153) of group 1 but 94% (102/108) of group 2. Multivariate analysis revealed that corticosteroid use (odds ratio [OR], 0.35; 95% confidence interval [CI], 0.16-0.75), older age (OR, 0.91; 95% CI, 0.860-0.98), and male sex (OR, 0.23; 95% CI, 0.07-0.74) were associated with a lower rate of high antibody titer acquisition after two doses of ChAdOx1-S nCoV-19. Waning of antibody titers was observed in only two of 46 patients who followed up twice after the third mRNA vaccine inoculation. CONCLUSION: Our findings suggest that the third dose of the mRNA vaccine could be beneficial in RA patients with risk factors including older age, male sex, and corticosteroid use after two doses of ChAdOx1-S nCoV-19.