Vasculitis Activity-Predicting Ability of IL-12 Family Cytokines in Patients with Microscopic Polyangiitis and Granulomatosis with Polyangiitis

Purpose@#The present study investigated and compared the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) activity-predicting ability of the serum concentrations of the four interleukin (IL)-12 family cytokines including IL-23, IL-27, IL-35, and IL-39 in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). @*Materials and Methods@#The present study included 70 patients with MPA and GPA. Clinical and laboratory data, particularly Birmingham Vasculitis Activity Score (BVAS), at the time of blood collection were obtained. The serum concentrations of IL-23, IL-27, IL-35, and IL-37 were measured using sera stored at -80°C. Patients were divided into two groups: the upper half of BVAS (BVAS ≥12) and the lower half of BVAS (BVAS <12). @*Results@#The serum concentrations of IL-23 and IL-27 reflected AAV activity. Patients with the upper half of BVAS exhibited significantly higher serum concentrations of IL-23 and IL-27 than those without. Patients with the serum concentrations of IL-23 ≥132.1 pg/mL or IL-27 ≥684.7 pg/mL exhibited higher frequency and risk for the upper half of BVAS than those without [relative risks (RR) 5.143 and RR 4.091, respectively]. The serum concentrations of IL-27 were associated with age ≥65 years and proteinase 3-ANCA (or C-ANCA) negativity, whereas, those of IL-23 were associated with MPA. However, the serum concentrations of IL-35 and IL-39 were not useful in predicting AAV activity in this study. @*Conclusion@#The present study is the first to demonstrate that among the various members of IL-12 family cytokines, the serum concentrations of IL-23 and IL-27 possess AAV activity-predicting ability.

Hepatic steatosis index at diagnosis has the potential for forecasting end-stage kidney disease in patients with antineutrophil cytoplasmic antibody-associated vasculitis

Objective@#This study evaluated whether the hepatic steatosis index (HSI) at antineutrophil cytoplasmic antibody-associated vasculitis (AAV) diagnosis could forecast poor outcomes during the disease course in AAV patients. @*Methods@#This study included 260 AAV patients. The equation for HSI is as follows: HSI=8×(alanine aminotransferase/aspartate aminotransferase)+body mass index+(2, diabetes mellitus)+(2, female). The cut-off of HSI was obtained using the receiver operating characteristic curve. @*Results@#The median age of the 260 patients was 59.5 years, and 65.0% were female. Among the continuous variables excluding the parameters composing the equation for HSI, HSI was significantly correlated with Birmingham vasculitis activity score, fivefactor score, haemoglobin, blood urea nitrogen, serum creatinine, and total cholesterol. Among poor outcomes, the area under the curve of HSI for end-stage renal disease (ESRD) was significant, and the cut-off of HSI for ESRD was set at ≤30.82. AAV patients with HSI ≤30.82 exhibited a significantly higher risk of ESRD (relative risk 3.489) and a significantly lower cumulative ESRD-free survival rate than those with HSI >30.82. @*Conclusion@#This study is the first to demonstrate that HSI at AAV diagnosis could forecast ESRD during the disease course in AAV patients.

Comparison of the 2022 ACR/EULAR Classification Criteria for Antineutrophil Cytoplasmic Antibody-Associated Vasculitis with Previous Criteria

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) comprises group of small vessel vasculitides, including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). In 2022, the American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR) jointly proposed new classification criteria for AAV (the 2022 ACR/EULAR criteria). In this review, we briefly summarize the 2022 ACR/EULAR criteria for GPA, MPA, and EGPA, and introduce our clinical experience with applying them to patients who were previously diagnosed with AAV based on three criteria: firstly, the classification criteria for GPA and EGPA proposed by the ACR in 1990; secondly, the algorithm for the classification of AAV and polyarteritis nodosa proposed by the European Medicines Agency algorithm in 2007 (the 2007 EMA algorithm); and thirdly, the revised International Chapel Hill Consensus Conference nomenclature of vasculitides in 2012 (the 2012 CHCC definitions). We found that concordance rate was highest in patients with MPA (96.6%), followed by those with EGPA (86.3%) and GPA (73.8%). In addition, compared to previous criteria, we noted several issues of the undervalued or overvalued items in the 2022 ACR/EULAR criteria for classifying AAV and provided several suggestions. To increase the diagnostic accuracy and reduce the discordance rate among the new and previous criteria for AAV, we suggest that the previous criteria should be considered together with the 2022 ACR/EULAR criteria when applying the classification criteria for AAV to patients suspected of AAV.

Implication of Serious Infections in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis for the First Cycle of Rituximab: A Pilot Study in a Single Korean Center

Objective@#This study investigated the clinical implications of serious infections in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) who received the first cycle of rituximab (RTX) during the first 6 months of follow-up. @*Methods@#The medical records of 36 AAV patients treated with RTX were reviewed. A weekly dose of 375 mg/m 2 RTX was administered for 4 weeks to all patients along with glucocorticoids. Serious infections were defined as those requiring hospitalization. All-cause mortality during the first 6 months of follow-up was counted. The follow-up duration was defined as the period from the first RTX infusion to 6 months after the first RTX infusion. @*Results@#The median age was 60.5 years, and 16 patients were male. Seven of 36 patients (19.4%) died and three AAV patients had five cases of serious infection such as enterocolitis, pulmonary aspergillosis, atypical pneumonia, cytomegalovirus pneumonia, and cellulitis. AAV patients with serious infections during the first 6 months of follow-up exhibited a significantly lower cumulative survival rate than those without serious infections (p<0.001). However, we found no independent predictor of serious infections using the Cox hazard model analysis. @*Conclusion@#Serious infection is an important predictor of all-cause mortality in Korean patients with AAV who received their first cycle of RTX but there were no significant variables to predict the occurrence of serious infections at the first RTX. Thus, in cases refractory to other induction therapies, RTX should be strongly considered, despite an increase in mortality rate.

Acute coronary syndrome in antineutrophil cytoplasmic antibody-associated vasculitis: a Korean single-centre cohort study

Objective@#This study investigated the incidence and patterns of the acute coronary syndrome (ACS) after AAV diagnosis and searched for the predictors of ACS in a single-centre cohort of Korean patients diagnosed with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). @*Methods@#A total of 262 patients with AAV were included in this study. ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), and unstable angina (UA) were defined as ACS in this study. Only ACS that occurred during or after AAV diagnosis was counted. @*Results@#The incidence of ACS in patients with AAV was 2.7% (7 patients), and the most common type of ACS was NSTEMI regardless of the affected site or the number of coronary arteries. Five patients with ACS were diagnosed with microscopic polyangiitis (MPA) and all of them had myeloperoxidase (MPO)-ANCA (or perinuclear [P]-ANCA), whereas the remaining two patients were diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA). Of the seven patients, 2 patients experienced ACS within the first year after AAV diagnosis, and 2 experienced ACS 5 years after AAV diagnosis. Among clinical variables, only the male sex was a predictor of ACS during the follow-up period in patients diagnosed with AAV. @*Conclusion@#The incidence of ACS was 2.7%, and the most common type of ACS was NSTEMI in Korean patients with AAV.

Association Between Idiopathic Cutaneous Leukocytoclastic Angiitis and ANCA-negative Microscopic Polyangiitis

Objective@#This study retrospectively reviewed the process of classifying antineutrophil cytoplasmic antibody (ANCA)-negative granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) in a cohort of patients with ANCA-associated vasculitis (AAV), and investigated the association between recurrent idiopathic cutaneous leukocytoclastic angiitis and ANCA-negative MPA. @*Methods@#The medical records of 242 patients with AAV were retrospectively reviewed. Of 49 patients with ANCA-negative AAV, 24 patients with ANCA-negative eosinophilic GPA (EGPA) were excluded, because ANCA positivity or negativity is not critical in classifying EGPA. Ultimately, 25 patients with ANCA-negative GPA and MPA were analysed in this study. The classification of GPA and MPA were based on the 2007 European Medicines Agency algorithm for AAV. @*Results@#The median age of patients with ANCA-negative GPA and MPA was 54.0 years and 24% were male. Of the 25 patients without ANCA, 8 patients were classified as GPA and 17 as MPA. Eight patients with ANCA-negative GPA were easily confirmed as definitive GPA. Fourteen of the 17 patients ANCA-negative MPA were classified as MPA based on histological features suggestive of AAV without granuloma formation and the absence of surrogate markers for GPA. Meanwhile, three of the patients that were ANCA-negative exhibited only recurrent idiopathic cutaneous leukocytoclastic angiitis without other major organs affected and thus were classified as possible MPA. Within one year, they were classified as definitive MPA based on ANCA positivity and/or renal histology. @*Conclusion@#Recurrent idiopathic cutaneous leukocytoclastic angiitis may be associated with ANCA-negative MPA in patients who exhibit cutaneous necrotising vasculitis.

Modified Body Mass Index at Diagnosis is a Useful Predictor of Mortality in Patients With Antineutrophil Cytoplasmic Antibody-associated Vasculitis

Objective@#We investigated whether modified body mass index (mBMI) at diagnosis could predict all-cause mortality during follow-up in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). @*Methods@#The medical records of 203 AAV patients with BMI ≥18.5 kg/m 2 were reviewed. mBMI was calculated using an equation: mBMI=BMI (kg/m 2 )×serum albumin (g/L). All-cause mortality was considered as a poor outcome, and the follow-up duration based on all-cause mortality was defined as the period from AAV diagnosis to death for deceased patients, and the period from AAV diagnosis to the last visit for surviving patients. @*Results@#The median age was 59.0 years (35.5% were male). The median BMI and mBMI were 22.8 kg/m2 and 813.2 kg · g/m2 · L.Twenty-five patients (12.3%) died. mBMI was well correlated with age, BVAS, FFS, erythrocyte sedimentation rate and C-reactive protein at diagnosis. Deceased patients exhibited significantly lower mBMI at diagnosis compared to surviving patients. AAV patients mBMI ≤570.1 kg g/m2 · L showed a significantly higher frequency of all-cause mortality (38.5% vs. 8.5%), and furthermore, exhibited a significantly higher risk for all-cause mortality than those with mBMI >570.1 kg · g/m2 · L (RR 6.750). mBMI ≤570.1 kg · g/m2 · L showed a significantly lower cumulative patients’ survival rate than those with mBMI >570.1 kg · g/m2 · L. In the multivariable Cox hazards model analysis, either serum albumin or mBMI was significantly associated with all-cause mortality in AAV patients. @*Conclusion@#In conclusion, mBMI ≤570.1 kg · g/m2 · L at diagnosis may be a useful predictor of all-cause mortality during followup additionally to serum albumin in AAV patients.

Serum Clusterin Level Could Reflect the Current Activity of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

Purpose@#We investigated whether serum clusterin levels could reflect the current antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)-specific indices. @*Materials and Methods@#Fifty-seven patients with AAV and 40 healthy controls were included in this study. AAV-specific indices included the Short-Form 36-Item Health Survey Physical and Mental Component Summaries (SF-36 PCS and MCS) scores, Birmingham vasculitis activity score (BVAS), five-factor score (FFS), and vasculitis damage index. Clinical and laboratory data and AAV-specific indices were obtained at blood collection. The highest tertile of BVAS (≥16) was defined as high activity of AAV. @*Results@#The median age of AAV patients was 64.0 years and 19 patients were male. SF-36 PCS score (r=0.328), SF-36 MCS score (r=0.289), BVAS (r=-0.404), erythrocyte sedimentation rate (r=-0.336), and C-reactive protein levels (r=-0.421) were significantly correlated with serum clusterin levels. In the multivariable linear regression analysis using AAV-specific indices and serum clusterin levels, both FFS (β=0.412) and serum clusterin levels (β=-0.250) were significantly associated with BVAS. When the optimal serum clusterin cut-off level for high activity of AAV was identified as 130.45 μg/mL, patients with serum clusterin level ≤130.45 μg/mL had a significantly higher risk for high activity of AAV than did those without (relative risk 7.194). Patients with AAV exhibited significantly lower serum clusterin levels than did healthy controls (168.2 μg/mL vs. 230.5 μg/mL). @*Conclusion@#Serum clusterin levels could reflect the current disease activity in patients with AAV.

The Efficacy of Mycophenolate Mofetil in Remission Maintenance Therapy for Microscopic Polyangiitis and Granulomatosis with Polyangiitis

Purpose@#The present study compared the efficacy of mycophenolate mofetil (MMF) with that of azathioprine (AZA) in Korean patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). @*Materials and Methods@#The medical records of 69 patients with MPA and GPA who received cyclophosphamide and subsequently received AZA or MMF for remission maintenance therapy were reviewed. All-cause mortality, relapse, end-stage renal disease (ESRD), cerebrovascular accident, and cardiovascular disease were evaluated as poor outcomes. Having a lower Birmingham Vasculitis Activity Score (BVAS) was defined as the lowest tertile of BVAS (BVAS ≤11 in this study). @*Results@#In comparative analysis of the occurrence of poor outcomes among patients taking AZA only, MMF only, and MMF after AZA, patients taking MMF only exhibited a significantly lower cumulative ESRD-free survival rate than patients taking AZA only (p=0.028). In terms of ESRD occurrence between the groups based on BVAS at diagnosis, among patients with MPA and GPA with higher BVAS at diagnosis, patients taking MMF only exhibited a significantly lower cumulative ESRD-free survival rate than those taking AZA only (p=0.047). Among patients with MPA and GPA with the lowest tertile of BVAS at diagnosis, cumulative ESRD-free survival rates did not differ. @*Conclusion@#With regard to ESRD occurrence, the efficacy of MMF in remission maintenance therapy was less effective than AZA in patients with MPA and GPA. However, among patients with lower BVAS, there was no difference in the occurrence of poor outcomes between patients taking MMF and those taking AZA.

Evaluation of body composition using computed tomography in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis

Background/Aims@#Measures of body composition, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and skeletal muscle area (SMA), are considered important prognostic factors in chronic diseases. The association of these measures with auto-inflammatory disorders, such as anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), remains unclear. We investigated the clinical significance of VAT, SAT, and SMA in patients with AAV. @*Methods@#Patients with AAV subjected to chest computed tomography (CT), abdominal CT, or positron emission tomography-CT on diagnosis of AAV were evaluated. Quantitative assessment of VAT, SAT, and SMA was performed at the third lumbar vertebral level and computed by summing the pixel attenuation for tissue-specific Hounsfield units in the corresponding region. Associations of VAT, SAT, and SMA with clinical and laboratory data and clinical outcome measures were evaluated. @*Results@#Of the 117 patients, 61 (52.1%) were classified as having microscopic polyangiitis, 28 (23.9%) as granulomatosis with polyangiitis, and 28 (23.9%) as eosinophilic granulomatosis with polyangiitis. VAT significantly correlated with age, weight, body mass index (BMI), and Birmingham Vasculitis Activity Score, whereas SAT correlated with weight, BMI, and creatinine levels. A significant association was found between SMA and age, height, weight, BMI, and the Five-Factor Score. Cox proportional hazards analysis showed that creatinine levels (odds ratio [OR], 1.346; 95% confidence interval [CI], 1.034 to 1.753; p = 0.027) and high VAT (OR, 7.137; 95% CI, 1.343–37.946; p = 0.021) were independently associated with all-cause mortality during follow-up. @*Conclusions@#Evaluation of VAT using CT is useful for estimating disease activity and all-cause mortality in patients with AAV.

Clinical features of Korean elderly patients with antineutrophil cytoplasmic antibody-associated vasculitis

Background/Aims@#We compared the clinical and laboratory data between elderly and non-elderly patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) at diagnosis; further, we investigated the predictors at diagnosis for all-cause mortality and end-stage renal disease (ESRD) occurrence during follow-up in Korean elderly patients with AAV. @*Methods@#We reviewed the medical records of 191 AAV patients regarding clinical manifestations and laboratory results at diagnosis and during follow-up. The follow-up duration was defined as the period from diagnosis to death for deceased patients or to the time of dialysis for ESRD patients, or to the last visit. Elderly (n = 67) and non-elderly (n = 124) patients were grouped based on an age threshold of 65 years. @*Results@#At diagnosis, elderly patients exhibited higher median Birmingham Vasculitis Activity Score (BVAS) and higher frequencies of ANCA positivity and pulmonary manifestations than non-elderly patients. Furthermore, elderly patients exhibited increased median white blood cell count, blood urea nitrogen (BUN), alkaline phosphatase, erythrocyte sedimentation rate, and C-reactive protein and decreased median hemoglobin. However, there were no significant differences in all-cause mortality and ESRD occurrence between elderly and non-elderly patients. Meanwhile, elderly patients exhibited lower cumulative patients’ and ESRD-free survival rates than non-elderly patients. In the multivariable Cox hazards model, BUN, creatinine and serum albumin at diagnosis were independent predictors for ESRD occurrence, whereas there were no independent predictors at diagnosis for all-cause mortality. @*Conclusions@#Elderly AAV patients exhibited substantially higher rates of all-cause mortality and ESRD occurrence during follow-up compared than non-elderly AAV patients.

KOBIO, the First Web-based Korean Biologics Registry Operated With a Unified Platform Among Distinct Disease Entities

The KOrean College of Rheumatology BIOlogics and targeted therapy (KOBIO) registry is a nationwide observational cohort that captures detailed data on exposure of patients to biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs). This registry was launched in December 2012 with an aim to prospectively investigate clinical manifestations and outcomes of patients with rheumatoid arthritis (RA), ankylosing spondylitis, and psoriatic arthritis who initiated a biologic or targeted synthetic DMARD or switched to another. Demographic data, disease activity, current treatment, adverse events, terms based on Medical Dictionary for Regulatory Activities, and so on are registered for patients who are then followed up annually in a web-based unified platform. The KOBIO registry also recruits and collects data of patients with RA on conventional DMARDs for comparison. As of today, more than 5,500 patients were enrolled from 47 academic and community Rheumatology centers across Korea. The KOBIO registry has evolved to become a powerful database for clinical research to improve clinical outcomes and quality of treatment.

Association of Serum Biomarkers With Pulmonary Involvement of Rheumatoid Arthritis Interstitial Lung Disease: From KORAIL Cohort Baseline Data

Objective@#The increase in mortality in rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) is well known. However, there are few studies on serum markers that can evaluate acute exacerbation or prognosis in RA-ILD patients. The purpose of this study was to identify the association between biomarkers and lung lesions in patients with RA-ILD. @*Methods@#We analyzed 153 patients with serum samples in a prospective, multicenter cohort of Korean RA-ILD patients. The serum levels of biomarkers, matrix metalloproteinase (MMP-7), surfactant protein-D (SP-D), and Krebs von den Lungen-6 (KL-6) were measured and correlated with forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO) and the results of computed tomography (CT). CT results were interpreted semi-quantitatively according to the extent of lung lesions (grade 1, 0%∼ 25%; grade 2, 26%∼50%; grade 3, 51%∼75%; grade 4, 76%∼100%). @*Results@#MMP-7, SP-D, and KL-6 were negatively correlated with FVC (MMP-7, r=−0.267, p=0.001; SP-D, r=−0.250, p=0.002; KL-6, r=−0.223, p=0.006) and DLCO (MMP-7, r=−0.404, p＜0.001; SP-D, r=−0.286, p=0.001; KL-6, r=−0.226, p=0.007). In addition, MMP-7, SP-D, and KL-6 tended to increase with higher grades of lung lesions on CT (MMP-7, p=0.013; SP-D, p＜0.001; KL-6, p＜0.001). @*Conclusion@#MMP-7, SP-D, and KL-6 can be used to evaluate the functional and anatomical status of lung involvement in the RA-ILD patients.

Male Sex Is a Significant Predictor of All-cause Mortality in Patients with Antineutrophil Cytoplasmic Antibodyassociated Vasculitis

Background@#We investigated and compared the initial clinical features at diagnosis and the poor outcomes during follow-up in Korean patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) based on sex. @*Methods@#The medical records of 223 immunosuppressive drug-naïve patients with AAV were reviewed. Age, body mass index (BMI), smoking history, AAV subtypes, ANCA positivity, clinical manifestations, Birmingham vasculitis activity score (BVAS), five-factor score (FFS), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) at diagnosis were collected. All-cause mortality, end-stage renal disease (ESRD), cerebrovascular accident (CVA) and cardiovascular disease (CVD) were assessed as the poor outcomes of AAV during follow-up. @*Results@#The median age was 59.0 years and 74 of 223 AAV patients (33.2%) were men.Among variables at diagnosis, male patients exhibited higher BMI than female. However, there were no differences in other demographic data, AAV subtypes, ANCA positivity, BVAS, FFS, ESR and CRP between the two groups. Male patients received cyclophosphamide more frequently, but there were no significant differences in the frequencies of the poor outcomes of AAV between the two groups. Male patients exhibited a significantly lower cumulative patients' survival rate than female patients during the follow-up period based on all-cause mortality (P = 0.037). In the multivariable analysis, both male sex (hazard ratio [HR], 2.378) and FFS (HR, 1.693) at diagnosis were significantly and independently associated with allcause mortality during follow-up. @*Conclusion@#Male sex is a significant and independent predictor of all-cause mortality in AAV patients.

Serum Clusterin Level Could Reflect the Current Activity of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

Purpose@#We investigated whether serum clusterin levels could reflect the current antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)-specific indices. @*Materials and Methods@#Fifty-seven patients with AAV and 40 healthy controls were included in this study. AAV-specific indices included the Short-Form 36-Item Health Survey Physical and Mental Component Summaries (SF-36 PCS and MCS) scores, Birmingham vasculitis activity score (BVAS), five-factor score (FFS), and vasculitis damage index. Clinical and laboratory data and AAV-specific indices were obtained at blood collection. The highest tertile of BVAS (≥16) was defined as high activity of AAV. @*Results@#The median age of AAV patients was 64.0 years and 19 patients were male. SF-36 PCS score (r=0.328), SF-36 MCS score (r=0.289), BVAS (r=-0.404), erythrocyte sedimentation rate (r=-0.336), and C-reactive protein levels (r=-0.421) were significantly correlated with serum clusterin levels. In the multivariable linear regression analysis using AAV-specific indices and serum clusterin levels, both FFS (β=0.412) and serum clusterin levels (β=-0.250) were significantly associated with BVAS. When the optimal serum clusterin cut-off level for high activity of AAV was identified as 130.45 μg/mL, patients with serum clusterin level ≤130.45 μg/mL had a significantly higher risk for high activity of AAV than did those without (relative risk 7.194). Patients with AAV exhibited significantly lower serum clusterin levels than did healthy controls (168.2 μg/mL vs. 230.5 μg/mL). @*Conclusion@#Serum clusterin levels could reflect the current disease activity in patients with AAV.

The Efficacy of Mycophenolate Mofetil in Remission Maintenance Therapy for Microscopic Polyangiitis and Granulomatosis with Polyangiitis

Purpose@#The present study compared the efficacy of mycophenolate mofetil (MMF) with that of azathioprine (AZA) in Korean patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). @*Materials and Methods@#The medical records of 69 patients with MPA and GPA who received cyclophosphamide and subsequently received AZA or MMF for remission maintenance therapy were reviewed. All-cause mortality, relapse, end-stage renal disease (ESRD), cerebrovascular accident, and cardiovascular disease were evaluated as poor outcomes. Having a lower Birmingham Vasculitis Activity Score (BVAS) was defined as the lowest tertile of BVAS (BVAS ≤11 in this study). @*Results@#In comparative analysis of the occurrence of poor outcomes among patients taking AZA only, MMF only, and MMF after AZA, patients taking MMF only exhibited a significantly lower cumulative ESRD-free survival rate than patients taking AZA only (p=0.028). In terms of ESRD occurrence between the groups based on BVAS at diagnosis, among patients with MPA and GPA with higher BVAS at diagnosis, patients taking MMF only exhibited a significantly lower cumulative ESRD-free survival rate than those taking AZA only (p=0.047). Among patients with MPA and GPA with the lowest tertile of BVAS at diagnosis, cumulative ESRD-free survival rates did not differ. @*Conclusion@#With regard to ESRD occurrence, the efficacy of MMF in remission maintenance therapy was less effective than AZA in patients with MPA and GPA. However, among patients with lower BVAS, there was no difference in the occurrence of poor outcomes between patients taking MMF and those taking AZA.

Evaluation of body composition using computed tomography in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis

Background/Aims@#Measures of body composition, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and skeletal muscle area (SMA), are considered important prognostic factors in chronic diseases. The association of these measures with auto-inflammatory disorders, such as anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), remains unclear. We investigated the clinical significance of VAT, SAT, and SMA in patients with AAV. @*Methods@#Patients with AAV subjected to chest computed tomography (CT), abdominal CT, or positron emission tomography-CT on diagnosis of AAV were evaluated. Quantitative assessment of VAT, SAT, and SMA was performed at the third lumbar vertebral level and computed by summing the pixel attenuation for tissue-specific Hounsfield units in the corresponding region. Associations of VAT, SAT, and SMA with clinical and laboratory data and clinical outcome measures were evaluated. @*Results@#Of the 117 patients, 61 (52.1%) were classified as having microscopic polyangiitis, 28 (23.9%) as granulomatosis with polyangiitis, and 28 (23.9%) as eosinophilic granulomatosis with polyangiitis. VAT significantly correlated with age, weight, body mass index (BMI), and Birmingham Vasculitis Activity Score, whereas SAT correlated with weight, BMI, and creatinine levels. A significant association was found between SMA and age, height, weight, BMI, and the Five-Factor Score. Cox proportional hazards analysis showed that creatinine levels (odds ratio [OR], 1.346; 95% confidence interval [CI], 1.034 to 1.753; p = 0.027) and high VAT (OR, 7.137; 95% CI, 1.343–37.946; p = 0.021) were independently associated with all-cause mortality during follow-up. @*Conclusions@#Evaluation of VAT using CT is useful for estimating disease activity and all-cause mortality in patients with AAV.

Clinical features of Korean elderly patients with antineutrophil cytoplasmic antibody-associated vasculitis

Background/Aims@#We compared the clinical and laboratory data between elderly and non-elderly patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) at diagnosis; further, we investigated the predictors at diagnosis for all-cause mortality and end-stage renal disease (ESRD) occurrence during follow-up in Korean elderly patients with AAV. @*Methods@#We reviewed the medical records of 191 AAV patients regarding clinical manifestations and laboratory results at diagnosis and during follow-up. The follow-up duration was defined as the period from diagnosis to death for deceased patients or to the time of dialysis for ESRD patients, or to the last visit. Elderly (n = 67) and non-elderly (n = 124) patients were grouped based on an age threshold of 65 years. @*Results@#At diagnosis, elderly patients exhibited higher median Birmingham Vasculitis Activity Score (BVAS) and higher frequencies of ANCA positivity and pulmonary manifestations than non-elderly patients. Furthermore, elderly patients exhibited increased median white blood cell count, blood urea nitrogen (BUN), alkaline phosphatase, erythrocyte sedimentation rate, and C-reactive protein and decreased median hemoglobin. However, there were no significant differences in all-cause mortality and ESRD occurrence between elderly and non-elderly patients. Meanwhile, elderly patients exhibited lower cumulative patients’ and ESRD-free survival rates than non-elderly patients. In the multivariable Cox hazards model, BUN, creatinine and serum albumin at diagnosis were independent predictors for ESRD occurrence, whereas there were no independent predictors at diagnosis for all-cause mortality. @*Conclusions@#Elderly AAV patients exhibited substantially higher rates of all-cause mortality and ESRD occurrence during follow-up compared than non-elderly AAV patients.

KOBIO, the First Web-based Korean Biologics Registry Operated With a Unified Platform Among Distinct Disease Entities

The KOrean College of Rheumatology BIOlogics and targeted therapy (KOBIO) registry is a nationwide observational cohort that captures detailed data on exposure of patients to biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs). This registry was launched in December 2012 with an aim to prospectively investigate clinical manifestations and outcomes of patients with rheumatoid arthritis (RA), ankylosing spondylitis, and psoriatic arthritis who initiated a biologic or targeted synthetic DMARD or switched to another. Demographic data, disease activity, current treatment, adverse events, terms based on Medical Dictionary for Regulatory Activities, and so on are registered for patients who are then followed up annually in a web-based unified platform. The KOBIO registry also recruits and collects data of patients with RA on conventional DMARDs for comparison. As of today, more than 5,500 patients were enrolled from 47 academic and community Rheumatology centers across Korea. The KOBIO registry has evolved to become a powerful database for clinical research to improve clinical outcomes and quality of treatment.

Association of Serum Biomarkers With Pulmonary Involvement of Rheumatoid Arthritis Interstitial Lung Disease: From KORAIL Cohort Baseline Data

Objective@#The increase in mortality in rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) is well known. However, there are few studies on serum markers that can evaluate acute exacerbation or prognosis in RA-ILD patients. The purpose of this study was to identify the association between biomarkers and lung lesions in patients with RA-ILD. @*Methods@#We analyzed 153 patients with serum samples in a prospective, multicenter cohort of Korean RA-ILD patients. The serum levels of biomarkers, matrix metalloproteinase (MMP-7), surfactant protein-D (SP-D), and Krebs von den Lungen-6 (KL-6) were measured and correlated with forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO) and the results of computed tomography (CT). CT results were interpreted semi-quantitatively according to the extent of lung lesions (grade 1, 0%∼ 25%; grade 2, 26%∼50%; grade 3, 51%∼75%; grade 4, 76%∼100%). @*Results@#MMP-7, SP-D, and KL-6 were negatively correlated with FVC (MMP-7, r=−0.267, p=0.001; SP-D, r=−0.250, p=0.002; KL-6, r=−0.223, p=0.006) and DLCO (MMP-7, r=−0.404, p＜0.001; SP-D, r=−0.286, p=0.001; KL-6, r=−0.226, p=0.007). In addition, MMP-7, SP-D, and KL-6 tended to increase with higher grades of lung lesions on CT (MMP-7, p=0.013; SP-D, p＜0.001; KL-6, p＜0.001). @*Conclusion@#MMP-7, SP-D, and KL-6 can be used to evaluate the functional and anatomical status of lung involvement in the RA-ILD patients.