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 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. @*Conclusions@#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.

Recovery and long-term renal outcome of patients with antineutrophil 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.

Anti-S1/RBD-Specific Antibody Formation After SARS-CoV-2Vaccination 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.

Incidence of rheumatic diseases during the COVID-19 pandemic in South Korea

Background/Aims@#The recent coronavirus disease 2019 (COVID-19) pandemic has been associated with changes in the epidemiology of not only infectious diseases but also several non-infectious conditions. This study investigated changes in the recorded incidence of various rheumatic diseases during the COVID-19 pandemic. @*Methods@#The number of patients for each disease from January 2016 to December 2020 was obtained from the Korean Health Insurance Review and Assessment Service database. We compared the incidence of nine rheumatic diseases (seropositive rheumatoid arthritis, systemic lupus erythematosus [SLE], idiopathic inflammatory myositis [IIM], ankylosing spondylitis [AS], systemic sclerosis, Sjögren’s syndrome, Behçet’s disease [BD], polymyalgia rheumatica, and gout) and hypertensive diseases to control for changes in healthcare utilisation before and after the COVID-19 outbreak. The disease incidence before and after the COVID-19 outbreak was compared using the autoregressive integrated moving average (ARIMA) and quasi- Poisson analyses. @*Results@#Compared with the predicted incidence in 2020 using the ARIMA model, the monthly incidence of SLE, BD, AS, and gout temporarily significantly decreased, whereas other rheumatic diseases and hypertensive diseases were within the 95% confidence interval (CI) of the predicted values in the first half of 2020. In age- and sex-adjusted quasi-Poisson regression analysis, the annual incidences of IIM (rate ratio [RR], 0.473; 95% CI, 0.307 to 0.697), SLE (RR, 0.845; 95% CI, 0.798 to 0.895), and BD (RR, 0.850; 95% CI, 0.796 to 0.906) were significantly decreased compared with those in the previous 4 years. @*Conclusions@#The recorded annual incidence of some rheumatic diseases, including IIM, SLE, and BD, decreased during the COVID-19 pandemic.

The Value of Thermal Imaging for Knee Arthritis: A Single-Center Observational Study

Purpose@#To compare (non-contact) thermal imaging with power Doppler (PD) for the evaluation of knee arthritis with joint effusion. @*Materials and Methods@#We enrolled patients with knee arthritis who were scheduled to undergo an arthrocentesis of the knee from April to December 2020 at a single tertiary hospital. A thermography camera, FLIR ONE Pro, was used to obtain both thermographic and digital images on subjects. For each subject, thermography, ultrasonography, arthrocentesis, and blood tests were conducted at the same study visit. Thermal imaging findings and clinical characteristics were compared by dividing the subjects into PD-positive and PD-negative groups on ultrasound. The receiver operating characteristic (ROC) curve analysis was used to determine the accuracy of PD positivity. @*Results@#A total of 30 knee arthritis patients were enrolled in this study. Knee temperature was significantly higher in PD-positive group compared to PD-negative group [maximum temperature (T max): 33.2°C vs. 30.5°C, p=0.025; minimum temperature (T min): 30.7°C vs. 27.0°C, p=0.015; average temperature (T ave): 32.1°C vs. 29.1°C, p=0.016]. Also, the joint fluid white blood cell count was considerably higher in PD-positive group than in PD-negative group (24556 cells/mm3 vs. 7840 cells/mm 3 , p=0.010). The area under the ROC curve of the point measurement of T max, T min, and T ave ranged between 0.764 and 0.790. @*Conclusion@#In this study, we found that high thermographic temperatures of the knee suggest a positive PD signal. Thus, thermography might be used as an adjuvant tool of PD for non-invasive evaluation of knee arthritis.

Initial Preserved Renal Function as a Predictor of Favorable Renal Response to Rituximab in Refractory or Relapsing Lupus Nephritis: A Single-center Cohort Study in Korea

Objective@#Previous studies investigating the beneficial effect of rituximab on lupus nephritis (LN) reported controversial results. There have been few reports of renal response to rituximab according to renal function. We investigated the efficacy of rituximab in refractory/relapsing LN and the role of renal function as a predictor of renal response. @*Methods@#From 2016 to 2019, we retrospectively reviewed 22 patients with refractory/relapsing LN receiving rituximab. Renal responses (complete and partial) at 6 and 12 months were compared between normal (glomerular filtration rate [GFR]≥90 mL/min/1.73 m2 , n=11) and decreased (GFR＜90 mL/min/1.73 m2 , n=11) GFR groups. Multivariate Cox regression analysis was used to assess predictors of renal response. @*Results@#At baseline, the decreased GFR group had a higher urine proteinuria to creatinine ratio (p=0.008) and proportion of refractory LN (p=0.010) and previous cyclophosphamide therapy (p=0.035) than the normal GFR group. The overall renal response rate was 45.5% (10 patients) at 6 months and 54.5% (12 patients) at 12 months. Renal response rates were higher in the normal GFR group (81.8% and 90.9% at 6 and 12 months, respectively) than in the decreased GFR group (9.1% and 18.2% at 6 and 12 months, respectively; p＜0.001). Normal GFR and anti-La were associated with renal response to rituximab, with hazard ratios of 9.256 (p=0.008) and 5.478 (p=0.041), respectively. @*Conclusion@#Rituximab is an effective therapy for refractory/relapsing LN, particularly in patients with preserved renal function.

Risk of Hepatitis B Virus (HBV) Reactivation in Patients with Immune-Mediated Inflammatory Diseases Receiving Biologics: Focus on the Timing of Biologics after Anti-HBV Treatment

Background/Aims@#Anti-hepatitis B virus (HBV) therapy is required for patients with HBV infection receiving biologics because of the high risk of HBV reactivation. However, it is unclear when to start biologics after anti-HBV treatment. We investigated the risk of HBV reactivation according to the timing of biologics initiation after anti-HBV treatment in immune-mediated inflammatory disease (IMID) patients with HBV infection. @*Methods@#We retrospectively evaluated the incidence of HBV reactivation in IMID patients who received biologics between July 2005 and April 2020. The patients were divided into two groups (within 1-week and after 1-week) according to the timing of biologics initiation after anti-HBV treatment. The cumulative probabilities and factors associated with HBV reactivation were evaluated. @*Results@#A total of 60 hepatitis B surface antigen-positive patients with IMID received biologics (within 1-week group, n=23 [38%]; after 1-week group, n=37 [62%]). During a median follow-up of 34 months (interquartile range, 20 to 74 months), three patients (5%) developed HBV reactivation. In univariate analysis, the timing of biologics after anti-HBV treatment was not significantly associated with the risk of HBV reactivation (hazard ratio, 0.657; 95% confidence interval, 0.059 to 7.327; p=0.733). The cumulative probabilities of HBV reactivation did not significantly differ according to the timing of biologics (p=0.731). @*Conclusions@#The risk of HBV reactivation was not significantly associated with the timing of biologics administration after anti-HBV treatment. Thus, biologics may be initiated early in patients with IMID undergoing treatment for HBV.

Predictive Factors for Rheumatoid Arthritis Flare After Switching From Intravenous to Subcutaneous Formulation of Tocilizumab in RealWorld Practice

Background@#To evaluate the incidence and related factors of rheumatoid arthritis (RA) flares after switching from intravenous tocilizumab (TCZ-IV) to subcutaneous tocilizumab (TCZSC) injection in stable RA patients. @*Methods@#We retrospectively evaluated the medical records of stable RA patients who used TCZ-IV for more than 6 months and switched to TCZ-SC between January 2013 and April 2020. RA flare was defined as an increase of more than 1.2 in the RA disease activity as assessed by the disease activity score in 28 joints. The factors associated with RA flare were evaluated by logistic regression analysis. @*Results@#Among 106 patients treated with TCZ-IV for > 6 months, 37 patients were switched to TCZ-SC after the acquisition of remission or low disease activity. RA flares occurred in 11 (29.7%) of patients who switched TCZ-SC. Results from the multivariable logistic analysis revealed that the dose of TCZ-IV per weight at switching (odds ratio [OR], 20.70; 95% confidence interval [CI], 2.22–192.84; P = 0.008) and methotrexate (MTX) non-use (OR, 8.53; 95% CI, 1.21–60.40; P = 0.032) were associated with the risk of RA flares after switching to TCZ-SC. Interestingly, most patients who switched back to TCZ-IV had their RA activity controlled again. @*Conclusion@#MTX non-use and high dose of TCZ-IV per weight were associated with a risk of RA flare after switching to TCZ-SC. RA patients with these factors need to be carefully observed for flare after switching from TCZ-IV to TCZ-SC.

Treatment Response to Idiopathic Retroperitoneal Fibrosis-associated Hydronephrosis With a Focus on IgG4/IgG3 Serum Concentration Ratio

Objective@#. Hydronephrosis, a common complication of idiopathic retroperitoneal fibrosis (iRPF), may lead to poor renal outcomes unless resolved in a timely manner. IgG4-related diseases characterized by elevated serum IgG4 levels are responsible for a few iRPF cases. However, the underlying immunologic features of most iRPF cases have not been clearly defined, and these cases exhibit varied responses to medical treatment. Thus, we investigated the predictive factors for hydronephrosis-associated outcomes among iRPF patients. @*Methods@#. We retrospectively included 18 iRPF patients with hydronephrosis in a tertiary referral hospital from 2012 to 2019. Hydronephrosis improvement was assessed on images taken 6 months after diagnosis. Categorical variables were compared using chi-square or Fisher’s exact test. Continuous variables were compared using Mann–Whitney U-test. @*Results@#. On follow-up images, 8 patients (44.4%) showed an improvement in hydronephrosis. Patients with improvement more frequently had reverse serum IgG4/IgG3 ratio (87.5% vs. 30%, p=0.025), abdominal aorta involvement (87.5% vs. 30%, p=0.025) and glucocorticoid treatment administration (87.5% vs. 30%, p=0.025) than those without improvement. The proportion of elevated serum IgG4 level did not differ between the two groups.Even in the 14 cases with normal serum IgG4 levels, reverse serum IgG4/IgG3 ratio was more frequently observed in patients with improvement than in those without improvement (83.3% vs. 12.5%, p=0.026). @*Conclusion@#. The reverse serum IgG4/IgG3ratio was associated with hydronephrosis improvement in iRPF patients, suggesting it to be a suitable serologic marker for predicting favourable responses to glucocorticoid treatment.

Comparison of Clinical, Angiographic Features and Outcome in Takayasu's Arteritis and Behçet's Disease With Arterial Involvement

OBJECTIVE: Takayasu's arteritis (TAK) is a vasculitis that primarily involves the aorta and its branches. In Behçet's disease (BD), systemic vasculitis is one of major manifestations. We aimed to compare clinical and angiographic features and outcome between TAK and BD with arterial involvement.METHODS: We retrospectively reviewed medical records of 206 TAK patients and 50 BD patients between 1995 and 2015. Angiographic lesions were evaluated via computed tomography, magnetic resonance imaging, and/or conventional angiography.RESULTS: Fever (30% vs. 9.2%, p<0.001) and arthralgia (36% vs. 7.3%, p<0.001) were more common in BD. C-reactive protein was higher in BD compared with TAK (5.85 mg/dL vs. 2.08 mg/dL, p<0.001). Stenosis (89.8% vs. 60%, p<0.001) and occlusion (65.5% vs. 32%, p<0.001) were more observed in TAK. In contrast, aneurysm was common in BD (62% vs. 20.9%, p<0.001). The carotid artery (73.3% vs. 30%, p<0.001), subclavian artery (71.4% vs. 16%, p<0.001), descending aorta (35% vs. 12%, p=0.002), renal artery (23.8% vs. 10%, p=0.032), superior mesenteric artery (18.4% vs. 4%, p=0.012), and brachiocephalic trunk (13.6% vs. 2%, p=0.020) were more commonly involved in TAK, whereas the femoral artery (10% vs. 2.4%, p=0.027) was more frequently involved in BD. During follow-up, arterial dissection (10% vs. 1.9%, p=0.016), rupture (12% vs. 0.5%, p<0.001), and arterial replacement/resection (66% vs. 9.7%, p<0.001) were more observed in BD.CONCLUSION: TAK differs from BD regarding clinical features and vascular involvement patterns. BD exhibits a higher rate of vascular complications.

Liver enzyme elevation in patients with ankylosing spondylitis treated with tumor necrosis factor inhibitors: a single-center historical cohort study

Background/Aims@#Tumor necrosis factor inhibitors (TNFi) have been known to induce liver enzyme elevation, sometimes associated with viral reactivation or toxic hepatitis. We evaluated the incidence and risk factors of TNFi-associated liver enzyme elevation in Korean ankylosing spondylitis (AS) patients who previously had normal liver enzymes. @*Methods@#Retrospectively, we collected data from the records of 363 AS patients treated with TNFi at a tertiary hospital from 2003 to 2017. Liver enzyme elevation was defined as abnormal elevation of aspartate aminotransferase and/or alanine aminotransferase levels on two or more consecutive visits. Patients with previously diagnosed liver disease were excluded. @*Results@#The incidence of liver enzyme elevation was 23.7% (occurring in 86 of 363 patients). The median duration of TNFi exposure before liver enzyme elevation was 3.72 months (interquartile range, 1.77 to 12.51). There was no difference in the occurrence of liver enzyme elevation with concomitant disease-modifying anti-rheumatic drugs and TNFi compared to TNFi alone (23.9% vs. 23.6%). In multivariate analysis, the hazard ratios for liver enzyme elevation were 4.62 (95% confidence interval [CI], 1.43 to 15.01) for male sex, 4.06 (95% CI, 2.11 to 7.84) for underlying non-alcoholic fatty liver disease, and 2.53 (95% CI, 1.38 to 4.64) for hyperlipidemia. After switching to another TNFi, the liver enzyme elevation was not normalized in nine of 13 patients. @*Conclusions@#Liver enzyme elevation was observed in a quarter of patients with AS receiving a TNFi. Male sex, non-alcoholic fatty liver disease, and hyperlipidemia were independent risk factors for liver enzyme elevation. Switching to another TNFi had a limited effect on restoring normal liver enzyme levels.

Clinical features and recurrent attack in gout patients according to serum urate levels during an acute attack

A substantial portion of gout patients have normal serum urate levels during an acute attack but data on the clinical characteristics and risk of recurrence compared with hyperuricemic patients are limited. Methods: In this retrospective cohort study, clinical features of normouricemic and hyperuricemic patients were compared. Multivariate analysis was performed to determine whether normouricemic patients were less likely to have a recurrent attack. Results: Among a total of 221 gout patients, 88 (39.8%) had normouricemia during an acute attack. Postsurgical gout (22.7% vs. 6.0%, p < 0.001), hemodialysis initiation (9.1% vs. 2.3%, p = 0.029) and inflammatory activity were higher in normouricemic patients than in hyperuricemic patients. The frequency of renal insufficiency was lower in normouricemic patients (25.0% vs. 53.4%, p < 0.001). However, the recurrence rate of gout attack was not different between the two groups (24.7% vs. 33.0%, p = 0.220). In multivariate analysis, female sex, history of urinary stone, presence of tophi, and use of thiazide were associated with increase of recurrent gout attack, but not with serum urate status during an acute attack (hazard ratio, 1.075; 95% confidence interval, 0.972 to 1.190; p = 0.159). Conclusions: Normouricemia during an acute gout attack was more frequently observed in postsurgical episodes, hemodialysis initiation and patients with preserved renal function. While higher inflammatory activity was observed in normouricemic patients, recurrent attack was not associated with serum urate levels during an acute attack. Thus, careful follow-up should be considered in gout patients regardless of serum urate levels during an acute attack.

Tocilizumab-induced Thrombocytopenia in Patients with Rheumatoid Arthritis

OBJECTIVE: Interlukin-6 (IL-6) increases platelet count during inflammation and may act in a manner similar to thrombopoietin. Tocilizumab is a monoclonal antibody of the IL-6 receptor and widely used in the treatment of rheumatoid arthritis (RA). Here, we evaluated the incidence of tocilizumab-induced thrombocytopenia and clinical factors associated with the development of thrombocytopenia. METHODS: Patients with RA, who were treated with tocilizumab and had exposed to other biologics previously in a tertiary hospital between January 2014 and December 2017, were retrospectively evaluated. We compared occurrence of thrombocytopenia between tocilizumab and previous biologics. Furthermore, the factors associated with thrombocytopenia were analyzed using logistic regression analysis. RESULTS: In total, 114 patients with RA were treated with tocilizumab for mean 90.5 weeks (interquartile range, 30.9~174.9). Thrombocytopenia was reported in 14 patients (12.3%) and it was higher rate compared with previous biologics. Most cases were grade 1 thrombocytopenia. Multivariate analysis showed that patient age (odds ratio [OR], 2.170; 95% confidence interval [CI], 1.118~4.211; p=0.022) and platelet count prior to treatment with tocilizumab (OR, 0.972; 95% CI, 0.954~0.990; p=0.002) were significantly associated with the development of thrombocytopenia. CONCLUSION: Old age is risk factor for developing tocilizumab-induced thrombocytopenia and higher platelet count prior to treatment is associated with lowering risk of development of thrombocytopenia. However, thrombocytopenia was tolerable.

Effects of Pregnancy and Delivery Methods on Change in Ankylosing Spondylitis Treatment Using the Korean Health Insurance Review and Assessment Service Claims Database

BACKGROUND: Women with ankylosing spondylitis (AS) show a higher rate of cesarean section (CS) compared with healthy women. In this study, we determined the effects of pregnancy and delivery methods on AS worsening by analyzing prescription patterns. METHODS: The subjects were women with AS aged 20–49 years listed in the Korean Health Insurance Review and Assessment Service claims database. Change in treatment was defined as change in prescriptions 1–2 years before delivery or 1 year after delivery. We compared change in prescriptions between AS women with delivery or without delivery (1:1 matched). Moreover, we evaluated change in prescriptions according to delivery method among AS women with delivery. RESULTS: A total of 6,821 women with AS were included. Women in the delivery group (n = 996) were younger and showed less drug use and lower comorbidity rates than those in the no delivery group. Change in prescriptions did not differ between the delivery and no delivery groups (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.56–1.05). Furthermore, the overall change in prescriptions did not significantly differ between vaginal delivery (VD) and CS (OR, 0.72; 95% CI, 0.45–1.14). CONCLUSION: The rate of change in prescriptions was comparable between AS patients with and without delivery. There was no association between the method of delivery and change in prescription. Therefore, pregnancy and VD may not be the factors associated with AS worsening.

Prominent Inflammatory Features of Monocytes/Macrophages in Acute Calcium Pyrophosphate Crystal Arthritis: a Comparison with Acute Gouty Arthritis

Calcium pyrophosphate (CPP) crystals can present as acute inflammatory arthritis which is known as an acute CPP crystal arthritis. Although monocytes/macrophages have been shown to play a role in the initiation of crystal-mediated inflammatory responses, differences in their phenotypes between acute CPP crystal arthritis and acute gouty arthritis have not yet been investigated. We examined the immunological characteristics of synovial monocytes/macrophages in patients with acute CPP crystal and acute gouty arthritis. CD14⁺CD3⁻CD19⁻CD56⁻ cell frequencies in synovial fluid mononuclear cells (SFMCs) were measured. Expression of pro- and anti-inflammatory cytokines and markers was determined. The SFMCs were dominated by a population of monocytes/macrophages in acute CPP crystal arthritis similar to that in acute gout. Synovial monocytes/macrophages showed the phenotypes of infiltrated monocytes as shown by expression of CD88, C-C chemokine receptor type 2, myeloid-related protein (MRP)8 and MRP14 but not proto-oncogene tyrosine-protein kinase MER. Comparatively, the CD14⁺ cells from patients with acute CPP crystal arthritis had similar high levels of IL-1β and TNF-α production but significantly lower expression of IL-10 and M2 marker (CD163). The monocytes/macrophages had the capacity to produce IL-8 in response to CPP crystals. Proinflammatory features were more dominant in monocytes/macrophages during acute CPP crystal arthritis than those during acute gouty arthritis.

Clinical features and prognoses of acute transverse myelitis in patients with systemic lupus erythematosus

BACKGROUND/AIMS@#Acute transverse myelitis (ATM) is a severe complication of systemic lupus erythematosus (SLE). This study evaluated the clinical factors related to outcome in patients with SLE-associated ATM.@*METHODS@#The medical records of patients diagnosed with SLE-associated ATM between January 1995 and January 2015 were reviewed. The patients were divided into two groups based on improvement of neurological deficits after treatment: favorable response group and unfavorable response group. During follow-up, the recurrence of ATM was also analyzed.@*RESULTS@#ATM was identified in 16 patients with SLE. All of the patients were treated with high doses of methylprednisolone (≥ 1 mg/kg daily). Although 12 patients (75%) recovered (favorable response group), four (25%) had persistent neurologic deficits (unfavorable response group) after the treatment. Compared to the favorable response group, significantly higher Systemic Lupus Erythematosus Disease Activity Index-2000, lower complement levels and initial severe neurologic deficits were found in the unfavorable response group. Among the 12 favorable response patients, five (41.7%) experienced recurrence of ATM during the followup. Patients (n = 5) who experienced relapse had a shorter duration of high-dose corticosteroid treatment (13.2 days vs. 32.9 days, p = 0.01) compared to patients who did not relapse. The mean duration of tapering-off the corticosteroid until 10 mg per day was significantly longer in non-relapse group (151.3 ± 60.8 days) than in relapse group (63.6 ± 39.4 days, p = 0.013).@*CONCLUSIONS@#Higher disease activity in SLE and initial severe neurologic deficits might be associated with the poor outcome of ATM. Corticosteroid slowly tapering-off therapy might be helpful in preventing the recurrence of ATM.

Treat-to-Target Strategy for Asian Patients with Early Rheumatoid Arthritis: Result of a Multicenter Trial in Korea

BACKGROUND: To evaluate the therapeutic benefits of the treat-to-target (T2T) strategy for Asian patients with early rheumatoid arthritis (RA) in Korea. METHODS: In a 1-year, multicenter, open-label strategy trial, 346 patients with early RA were recruited from 20 institutions across Korea and stratified into 2 groups, depending on whether they were recruited by rheumatologists who have adopted the T2T strategy (T2T group) or by rheumatologists who provided usual care (non-T2T group). Data regarding demographics, rheumatoid factor titer, anti-cyclic citrullinated peptide antibody titer, disease activity score of 28 joints (DAS28), and Korean Health Assessment Questionnaire (KHAQ) score were obtained at baseline and after 1 year of treatment. In the T2T group, the prescription for disease-modifying antirheumatic drugs was tailored to the predefined treatment target in each patient, namely remission (DAS28 < 2.6) or low disease activity (LDA) (2.6 ≤ DAS28 < 3.2). RESULTS: Data were available for 163 T2T patients and 162 non-T2T patients. At the end of the study period, clinical outcomes were better in the T2T group than in the non-T2T group (LDA or remission, 59.5% vs. 35.8%; P < 0.001; remission, 43.6% vs. 19.8%; P < 0.001). Compared with non-T2T, T2T was also associated with higher rate of good European League Against Rheumatism response (63.0% vs. 39.8%; P < 0.001), improved KHAQ scores (−0.38 vs. −0.13; P = 0.008), and higher frequency of follow-up visits (5.0 vs. 2.0 visits/year; P < 0.001). CONCLUSION: In Asian patients with early RA, T2T improves disease activity and physical function. Setting a pre-defined treatment target in terms of DAS28 is recommended.

Rapid onset of efficacy predicts response to therapy with certolizumab plus methotrexate in patients with active rheumatoid arthritis

BACKGROUND/AIMS: The objective of this study was to determine the efficacy and safety of add-on therapy with certolizumab pegol (CZP) in active rheumatoid arthritis (RA) patients of a single ethnicity. METHODS: In this 24-week, phase 3, randomized, double-blind, placebo-controlled trial, eligible patients (n = 127) were randomized 2:1 to subcutaneous CZP + methotrexate (MTX; 400 mg at week 0, 2, and 4 followed by 200 mg every 2 weeks) or placebo + MTX. RESULTS: At week 24, the American College of Rheumatology criteria for 20% (ACR20) response rate was significantly greater with CZP + MTX than with placebo (66.7% vs. 27.5%, p < 0.001). Differences in ACR20 response rates for CZP vs. placebo were significant from week 1 (p < 0.05) and remained significant through week 24. The CZP group reported significant improvement in physical function and disability compared to the placebo group (p < 0.001) at week 24, as assessed by Korean Health Assessment Questionnaire-Disability Index (KHAQ-DI). Post hoc analysis indicated that the proportion of patients who had ACR70 responses, Disease Activity Score 28 (DAS28) low disease activity, and DAS28 remission at week 24 was greater in CZP + MTX-treated patients who achieved a decrease in DAS28 ≥ 1.2 (43.8%) at week 4 than in nonresponders. Among 18 (22.2%) and 14 patients (35.0%) in CZP and placebo groups who had latent tuberculosis (TB), none developed active TB. Most adverse events were mild or moderate. CONCLUSIONS: CZP treatment combined with MTX in active RA patients with moderate to severe disease activity and an inadequate response to MTX resulted in rapid onset of efficacy, which is associated with better clinical outcome at week 24 and has an acceptable safety profile, especially in an intermediate TB-burden population.

Is the Serum Uric Acid Level Independently Associated with Incidental Urolithiasis?

OBJECTIVE: Urolithiasis is one of the manifestations of gout and the risk is higher in gouty patients. On the other hand, an independent association between the urinary stone and serum uric acid (UA) level has not been established. This study examined whether the risk of urolithiasis increases with increasing serum UA level. METHODS: Among the people who visited a tertiary hospital from 2010 to 2013, 13,964 individuals who underwent both ultrasonography and a laboratory test were recruited in the study. The risk of urolithiasis on ultrasonography was analyzed in association with the serum UA level by multiple logistic regression analysis with an adjustment for age, sex, body mass index, estimated glomerular filtration rate, and known underlying diseases, including diabetes mellitus and hypertension. RESULTS: Among the 6,743 men (48.3%) and 7,221 women (51.7%), the age was 51.3±13.5 and the serum UA level was 4.5±2.1 mg/dL. Hyperuricemia (>7 mg/dL) was observed in 1,381 cases (9.9%). Urolithiasis was detected by ultrasonography in 608 cases (4.4%). The detection rates of urolithiasis in individuals with hyperuricemia and normouricemia were 5.9% and 4.1%, respectively (p=0.001). Multiple logistic regression analysis showed that individuals with hyperuricemia had a significantly higher risk of urolithiasis (adjusted odds ratio [OR]=1.54; 95% confidence interval [CI], 1.20~1.96; p=0.001). A comparison of the highest with the lowest quartile of serum UA revealed a multivariable-adjusted OR of 3.17 (95% CI, 1.98~5.11) for men and 1.79 (1.08~2.93) for women. CONCLUSION: These results suggest that individuals with a higher serum UA level have a higher risk of subclinical and clinical urolithiasis.

Role of IL-32 Gamma on Bone Metabolism in Autoimmune Arthritis

IL-32 acts as a pro-inflammatory cytokine by inducing the synthesis of inflammatory molecules as well as promoting the morphological changes involved in the transformation of monocytes into osteoclasts (OCs). Evaluation of the functions of IL-32 has mainly focused on its inflammatory properties, such as involvement in the pathogenesis of various autoimmune diseases. Recently, IL-32 was shown to be involved in bone metabolism, in which it promotes the differentiation and activation of OCs and plays a key role in bone resorption in inflammatory conditions. IL-32γ also regulates bone formation in conditions such as ankylosing spondylitis and osteoporosis. In this review, we summarize the results of recent studies on the role of IL-32γ in bone metabolism in inflammatory arthritis.