Relapse risk factors and clinical characteristics of idiopathic inflammatory myopathies in 105 patients.

OBJECTIVE: To identify the risk factors for relapse of idiopathic inflammatory myopathies (IIMs). METHODS: Patients who were newly diagnosed with IIMs and underwent muscle biopsy between 2000 and 2017 at Asan Medical Center were retrospectively reviewed. The relapse of IIMs was defined as the recurrence of muscle or cutaneous manifestations with a ≥50% increase in glucocorticoid dosage after reaching the low-dose glucocorticoid phase with clinically significant improvement. The factors associated with the relapse of IIMs were investigated by Cox proportional hazards analysis. RESULTS: Of 105 patients with IIMs, relapse was observed in 65 patients (62%). The titer of antinuclear antibody (ANA) was higher in the relapse group than in the non-relapse group (P = 0.033). Multivariable analysis showed that the relapse of IIMs was significantly associated with histopathologic features consistent with IIMs (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.01-2.83, P = 0.045) and the use of immunosuppressants before relapse (HR, 0.50; 95% CI, 0.29-0.86, P = 0.013). Doubling of ANA titer was also associated with relapse, albeit without statistical significance (HR, 1.13; 95% CI, 1.00-1.27, P = 0.052). CONCLUSION: In patients with IIMs, the use of immunosuppressants had a significant negative association with relapse. Administering immunosuppressants from the early period during the initial glucocorticoid tapering phase may be useful in reducing the risk of relapse in patients with IIMs. Key Points • Since idiopathic inflammatory myopathies (IIMs) have a low prevalence, it is poorly understood which factors are associated with the relapse of IIMs. • In this study, about two-thirds of 105 patients with IIMs experienced a relapse of IIMs. • The risk of relapse in patients with IIMs was negatively associated with the use of immunosuppressants during glucocorticoid tapering and low-dose glucocorticoid phase. • Even in less severe cases, the use of immunosuppressants might be a good option for the management of IIMs.

Prevalence and Risk Factors of COVID-19 Reinfection in Patients with Rheumatoid Arthritis: A Retrospective Observational Study.

PURPOSE: To identify the prevalence and risk factors of coronavirus disease 2019 (COVID-19) reinfection in patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: This study retrospectively analyzed patients with RA with a documented COVID-19 infection between January 2021 and December 2022 at a tertiary hospital in Seoul, South Korea. Reinfection was defined as a subsequent positive test result for severe acute respiratory syndrome coronavirus 2 at least 3 months after the initial infection. Cox proportional hazards models with backward elimination were employed to assess the association between potential risk factors and risk of reinfection. RESULTS: Of 351 included patients with RA {female, 81.5%; median age, 58.0 years [interquartile range (IQR), 48.0-66.0]}, 252 (71.8%) were treated with methotrexate and 12 (3.4%) received leflunomide during the initial infection. Over a median follow-up of 1.5 (IQR, 1.1-1.6) years, 43 (12.3%) patients experienced reinfection, equating to an incidence rate of 8.97 per 100 patient-years. The median time interval between infections was 0.8 (IQR, 0.6-1.2) years. Among the risk factors, leflunomide use showed a significant association with reinfection (hazard ratio, 2.968; 95% confidence interval, 1.057-8.335; p=0.039). However, no significant changes occurred in disease activity following reinfection [disease activity score using 28 joints: baseline median, 2.3 (IQR, 1.9-2.8); post-reinfection median, 2.3 (IQR, 1.8-2.6), p for change=0.895]. CONCLUSION: In this retrospective cohort study of patients with RA with COVID-19 infection, approximately 12% of patients experienced reinfection without significant change in disease activity. Leflunomide use was associated with a higher risk of reinfection.

Lupus flare and recurrent lupus nephritis following kidney transplantation in patients with lupus nephritis.

BACKGROUND: Clinical manifestations and risk factors associated with systemic lupus erythematosus (SLE) flares, including recurrent lupus nephritis (LN), in patients with LN who undergo kidney transplantation have been unclear. METHODS: Kidney transplant recipients with LN from January 1995 to December 2021 were included in this study. A disease flare was defined as either an increase in the non-renal SLE disease activity index score or the presence of biopsy-proven recurrent LN. RESULTS: Among a total of 93 patients with LN who underwent kidney transplantation, 11 patients (11.8%) experienced SLE flares during a median follow-up period of 76.9 months (IQR, 43.0-122.4). The most common clinical manifestations of SLE flares were recurrent LN (4/11, 36.4%) and hematologic manifestations (4/11, 36.4%). Patients who had flares had significantly higher anti-double-stranded DNA (anti-dsDNA) antibody titers both before and after transplantation. Furthermore, an increased anti-dsDNA antibody level before transplantation was associated with a high risk of an SLE flare (HR, 1.030; p = .008). Conversely, preemptive transplantation was associated with a lower risk of a flare (HR, 0.617; p = .026). The rate of patient death-censored graft survival was found to be considerably lower in patients with recurrent LN than in those without LN. CONCLUSIONS: Approximately 10% of patients with LN experienced an SLE flare after transplantation, with recurrent LN being the most frequent manifestation. Anti-dsDNA antibody titers before transplantation were significantly related to the risk of an SLE flare. Notably, preemptive transplantation was associated with a reduced risk of flares following transplantation.

Anti-protein phosphatase magnesium-dependent 1A-IgM levels in patients with active ankylosing spondylitis: a potential biomarker.

BACKGROUND: Ankylosing spondylitis (AS) has been known to have auto-inflammatory nature; hence, the efficacy of autoantibodies is low. However, studies on autoantibodies are ongoing, with some studies showing associations. Previous studies showed that anti-protein phosphatase magnesium-dependent 1A (PPM1A) IgG was increased in patients with AS and associated with radiographic progression. However, the diagnostic usefulness was limited due to relatively low sensitivity and specificity. This pilot study evaluated the diagnostic utility of anti-PPM1A-IgM and anti-PPM1A-IgG in patients with active AS. METHODS: Serum samples were obtained from the registry cohort of a single tertiary center in Korea. Serum levels of anti-PPM1A-IgG/IgM were measured by direct ELISA. Receiver operating characteristic (ROC) analysis was used to predict the diagnostic sensitivity and specificity of serum anti-PPM1A-IgG/IgM. RESULTS: Samples were collected from 28 patients with active AS, 16 healthy controls (HCs), and 28 patients with rheumatoid arthritis (RA). Although total serum IgM was lower in the RA and AS groups than in the HC group, anti-PPM1A-IgM was significantly lower in the AS group than in the other groups. In evaluating the diagnostic utility of anti-PPM1A-IgG/IgM for AS patients compared with HCs, the area under the curve (AUC) of anti-PPM1A-IgM was 0.998 (sensitivity 96.4%, specificity 100.0%). When ROC analysis of anti-PPM1A-IgM for AS patients compared with RA patients was conducted, sensitivity was 78.6% and specificity was 71.4%, with an AUC of 0.839. CONCLUSION: Decreased anti-PPM1A-IgM levels in AS patients suggests a potential role for anti-PPM1A-IgM in the diagnosis of active AS.

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 1 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 1 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 1 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 1 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.

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.

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.

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.

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.

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.

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.

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.

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.