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Background/Aims@#We aimed to compare the effectiveness and safety of Janus kinase inhibitors (JAKi) vs. biologic disease- modifying antirheumatic drugs (bDMARD) in Korean patients with rheumatoid arthritis (RA) who had an inadequate response to conventional synthetic DMARDs. @*Methods@#A quasi-experimental, multi-center, prospective, non-randomized study was conducted to compare response rates between JAKi and bDMARDs in patients with RA naïve to targeted therapy. An interim analysis was performed to estimate the proportion of patients achieving low disease activity (LDA) based on disease activity score (DAS)–28– erythroid sedimentation rate (ESR) (DAS28-ESR) at 24 weeks after treatment initiation and to evaluate the development of adverse events (AEs). @*Results@#Among 506 patients enrolled from 17 institutions between April 2020 and August 2022, 346 (196 JAKi group and 150 bDMARD group) were included in the analysis. After 24 weeks of treatment, 49.0% of JAKi users and 48.7% of bDMARD users achieved LDA (p = 0.954). DAS28-ESR remission rates were also comparable between JAKi and bDMARD users (30.1% and 31.3%, respectively; p = 0.806). The frequency of AEs reported in the JAKi group was numerically higher than that in the bDMARDs group, but the frequencies of serious and severe AEs were comparable between the groups. @*Conclusions@#Our interim findings reveal JAKi have comparable effectiveness and safety to bDMARDs at 24 weeks after treatment initiation.
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Background/Aims@#We evaluated nailfold capillaroscopy (NFC) of interstitial pneumonia with autoimmune features (IPAF) and compared it with that of patients with connective tissue disease-interstitial lung disease (CTD-ILD) and idiopathic interstitial pneumonia (IIP). @*Methods@#Patients with newly diagnosed as ILD were evaluated using NFC. Baseline demographic, clinical, serological, and high-resolution CT findings were collected. NFC was semi-quantitatively scored with six domains ranging from 0 to 18. In addition, the overall patterns (sclerodermaon-scleroderma patterns) were determined. @*Results@#A total of 81 patients (31 with CTD-ILD, 18 with IPAF, and 32 with IIP) were included. The non-specific interstitial pneumonia pattern was the most common ILD pattern in the CTD-ILD and IPAF groups, whereas the usual interstitial pneumonia pattern was the most common in the IIP group. The semi-quantitative score of the CTD-ILD group was higher than that of the IPAF or IIP groups (5.8 vs 4.2 vs 3.0, p < 0.001, respectively). Giant capillaries and haemorrhages were more frequently present in the CTD-ILD and IPAF groups than in the IIP group. A scleroderma pattern was present in 27.8% of the IPAF group, whereas none of the IIP patients showed a scleroderma pattern. @*Conclusions@#NFC findings may be useful in classifying patients with ILD into CTD-ILD/IPAF/IIP.
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Objectives@#This study used the Korean National Health and Nutrition Examination Survey (KNHANES) to determine the association between fractures and low muscle mass. @*Methods@#This cross-sectional study used the 2010–2011 KNHANES data. Low muscle mass was defined as (appendicular skeletal muscle mass [kg]/Height2 [m2 ]) < 5.45 kg/m2 , which is < 2 SD below the sex-specific mean of a young reference group. Patients with T-scores between –1.0 and –2.5 indicated osteopenia, whereas those with T-scores lower than –2.5 indicated osteoporosis. @*Results@#Out of 1,306 women enrolled in the study, 330 were diagnosed with low muscle mass according to the abovementioned diagnostic criterion. The prevalence of fractures at various sites was significantly higher in postmenopausal women with low muscle mass than in those without low muscle mass (relative risk [RR], 1.64; odds ratio [OR], 1.62; 95% confidence interval [CI], 1.06–2.48; P = 0.027). Furthermore, the prevalence of fractures was increased by the presence of osteopenia or osteoporosis in addition to low muscle mass (RR, 1.59; OR, 1.60; 95% CI, 1.02–2.49; P = 0.039) and by osteoporosis only (RR, 2.12; OR, 2.29; 95% CI, 1.11–4.70; P = 0.025). @*Conclusions@#Fracture was more prevalent in postmenopausal women with low muscle mass than in those without low muscle mass.This finding is consistent in a subgroup analysis that included women who had osteoporosis or osteopenia. Moreover, the risk of fractures increased as low muscle mass worsened.
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Our understanding and management of rheumatoid arthritis (RA) have greatly improved, but perioperative and anesthetic management remain challenging. RA is not limited to joints; systemic evaluation is thus required when planning perioperative management. Especially, careful airway evaluation is needed; management of airway-related arthritis is challenging. A multidisciplinary approach is essential to prevent complications without exacerbating RA disease activity. Guidelines published in 2017 are available for perioperative management of anti-rheumatic medication in patients with rheumatic diseases undergoing elective total hip or total knee arthroplasty. However, the guidelines focus only on anti- rheumatic medications, and do not consider all aspects of perioperative management (including anesthesia). Here, we discuss the perioperative and anesthetic management of patients with RA.
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Interstitial pneumonia with autoimmune feature (IPAF) is a recently established disease entity that is comprised of interstitial lung diseases with evidence of autoimmune features but that does not fulfill the criteria for definite autoimmune rheumatic diseases. The classification criteria for IPAF were defined by the European Respiratory Society and American Thoracic Society in 2015. However, further studies to establish IPAF subgroups and treatment modalities for each subgroup are still needed. In this review, we discuss recent advances regarding IPAF and raise critical points for the diagnosis and management of patients with IPAF from the perspective of rheumatologists.
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Adult-onset Still’s disease (AOSD) is an obscure disease that is usually diagnosed after the exclusion of other febrile diseases, including other autoimmune, infectious, and malignant diseases. Although definitive diagnostic criteria and treatment guidelines for AOSD are thus far lacking, the typical manifestations of AOSD have been identified and effective medications for remission and maintenance have been proposed. The pathophysiology of the AOSD is unclear, but diagnostic criteria and treatment guidelines for AOSD can be established by determining its core etiology and conducting clinical trials of previously tested immunosuppressants and biologics.
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Interstitial pneumonia with autoimmune feature (IPAF) is a recently established disease entity that is comprised of interstitial lung diseases with evidence of autoimmune features but that does not fulfill the criteria for definite autoimmune rheumatic diseases. The classification criteria for IPAF were defined by the European Respiratory Society and American Thoracic Society in 2015. However, further studies to establish IPAF subgroups and treatment modalities for each subgroup are still needed. In this review, we discuss recent advances regarding IPAF and raise critical points for the diagnosis and management of patients with IPAF from the perspective of rheumatologists.
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Adult-onset Still’s disease (AOSD) is an obscure disease that is usually diagnosed after the exclusion of other febrile diseases, including other autoimmune, infectious, and malignant diseases. Although definitive diagnostic criteria and treatment guidelines for AOSD are thus far lacking, the typical manifestations of AOSD have been identified and effective medications for remission and maintenance have been proposed. The pathophysiology of the AOSD is unclear, but diagnostic criteria and treatment guidelines for AOSD can be established by determining its core etiology and conducting clinical trials of previously tested immunosuppressants and biologics.
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Background/Aims@#The present study aimed to investigate whether tocotrienol regulates interleukin 17 (IL-17)-induced osteoclastogenesis in rheumatoid arthritis (RA). @*Methods@#We evaluated the effect of tocotrienol on IL-17-induced receptor activator of nuclear factor kappa B ligand (RANKL) production using RA fibroblast-like synoviocyte (FLS), together with real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Osteoclast differentiation was confirmed after culturing IL-17-treated RA FLS and Th17 cells with tocotrienol and monocytes. We analyzed the suppressive effect of tocotrienol on Th17 cells percentage or Th17-cytokine levels among peripheral blood mononuclear cells using flow cytometry. @*Results@#We found that IL-17 stimulated FLS to produce RANKL and tocotrienol decreased this IL-17-induced RANKL production. Tocotrienol decreased the IL-17-induced activation of mammalian target of rapamycin, extracellular signal-regulated kinase, and inhibitor of kappa B-alpha. When monocytes were incubated with IL-17, RANKL, IL-17-treated FLS or Th17 cells, osteoclasts were differentiated and tocotrienol decreased this osteoclast differentiation. Tocotrienol reduced Th17 cell differentiation and the production of IL-17 and sRANKL; however, tocotrienol did not affect Treg cell differentiation. @*Conclusions@#Tocotrienol inhibited IL-17- activated RANKL production in RA FLS and IL-17-activated osteoclast formation. In addition, tocotrienol reduced Th17 differentiation. Therefore, tocotrienol could be a new therapeutic choice to treat bone destructive processes in RA.
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Background/Aims@#Sorafenib is the first approved systemic treatment for advanced hepatocellular carcinoma (HCC). However, its clinical utility is limited, especially in Asian countries. Several reports have suggested the survival benefits of hepatic arterial infusion chemotherapy (HAIC) for advanced HCC with main portal vein tumor thrombosis (PVTT). This study aimed to compare the efficacy of sorafenib-based therapy with that of HAIC-based therapy for advanced HCC with main PVTT. @*Methods@#Advanced HCC patients with main PVTT treated with sorafenib or HAIC between 2008 and 2016 at Korea University Medical Center were included. We evaluated overall survival (OS), time-to-progression (TTP), and the disease control rate (DCR). @*Results@#Seventy-three patients were treated with sorafenib (n=35) or HAIC (n=38). Baseline characteristics were not significantly different between groups, except the presence of solid organ metastasis (46% vs 5.3%, p<0.001). The median OS time was not significantly different between the groups (6.4 months vs 10.0 months, p=0.139). TTP was longer in the HAIC group than in the sorafenib group (2.1 months vs 6.2 months, p=0.006). The DCR was also better in the HAIC group than in the sorafenib group (37% vs 76%, p=0.001). Subgroup analysis, which excluded patients with extrahepatic solid organ metastasis, showed the same trends for the median OS time (8.8 months vs 11.1 months, p=0.097), TTP (1.9 months vs 6.0 months, p<0.001), and DCR (53% vs 81%, p=0.030). @*Conclusions@#HAIC-based therapy may be an alternative to sorafenib for advanced HCC with main PVTT by providing longer TTP and a better DCR.
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Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory arthritis, and the complex interaction and activation of innate and adaptive immune cells are involved in RA pathogenesis. Mast cells (MCs) are one of the tissue-resident innate immune cells, and they contribute to RA pathogenesis. In the present review, the evidence of the pathologic role of MC in RA is discussed based on human and animal data. In addition, the potential role of MC in RA pathogenesis and the research area that should be focused on in the future are suggested.
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BACKGROUND/AIMS: This study aimed to determine the regulatory role of N-acetyl-l-cysteine (NAC), an antioxidant, in interleukin 17 (IL-17)-induced osteoclast differentiation in rheumatoid arthritis (RA). METHODS: After RA synovial fibroblasts were stimulated by IL-17, the expression and production of receptor activator of nuclear factor κ-B ligand (RANKL) was determined by real-time polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). Osteoclastogenesis was also determined after co-cultures of IL-17-stimulated RA synovial fibroblasts, Th17 cells and various concentrations of NAC with monocytes. After human peripheral CD4⁺ T cells were cultured with NAC under Th17 condition, IL-17, interferon γ, IL-4, Foxp3, RANKL, and IL-2 expression and production was determined by flow cytometry or ELISA. RESULTS: When RA synovial fibroblasts were stimulated by IL-17, IL-17 stimulated the production of RANKL, and NAC reduced the IL-17-induced RANKL production in a dose-dependent manner. NAC decreased IL-17-activated phosphorylation of mammalian target of rapamycin, c-Jun N-terminal kinase, and inhibitor of κB. When human peripheral blood CD14⁺ monocytes were cultured with macrophage colony-stimulating factor and IL-17 or RANKL, osteoclasts were differentiated, and NAC reduced the osteoclastogenesis. After human peripheral CD4⁺ T cells were co-cultured with IL-17-pretreated RA synovial fibroblasts or Th17 cells, NAC reduced their osteoclastogenesis. Under Th17 polarizing condition, NAC decreased Th17 cell differentiation and IL-17 and RANKL production. CONCLUSIONS: NAC inhibits the IL-17-induced RANKL production in RA synovial fibroblasts and IL-17-induced osteoclast differentiation. NAC also reduced Th17 polarization. NAC could be a supplementary therapeutic option for inflammatory and bony destructive processes in RA.
Subject(s)
Humans , Acetylcysteine , Arthritis, Rheumatoid , Coculture Techniques , Enzyme-Linked Immunosorbent Assay , Fibroblasts , Flow Cytometry , Interferons , Interleukin-17 , Interleukin-2 , Interleukin-4 , JNK Mitogen-Activated Protein Kinases , Macrophage Colony-Stimulating Factor , Monocytes , Osteoclasts , Osteogenesis , Phosphorylation , RANK Ligand , Real-Time Polymerase Chain Reaction , Sirolimus , T-Lymphocytes , Th17 CellsABSTRACT
Mycophenolate mofetil (MMF) is an immunosuppressive agent used to treat severe lupus, including lupus nephritis. Common adverse effects of MMF include gastrointestinal and hematological manifestations; however, cardiac toxicity in association with MMF has not been reported. We present a 21-year-old woman with lupus nephritis who developed ventricular tachycardia 2 hours after an overdose of MMF (34 g). Ventricular bigeminy was documented 12 hours after the MMF overdose. Transthoracic echocardiography showed no evidence of structural heart disease. The ventricular arrhythmia was successfully treated with potassium replacement, hydration, and cholestyramine. This case suggests that an overdose of MMF can induce ventricular tachycardia, and electrocardiogram monitoring is critical to identify this rare cardiac complication of MMF.
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The purpose of this study was to determine the regulatory role of intravenous Ig (IVIg) in Th17 cytokine–induced RANK ligand (RANKL) expression and osteoclast (OC) differentiation from OC precursors (pre-OC). Human CD14⁺ monocytes were isolated and stimulated by Th17 cytokines (IL-17, IL-21, and IL-22) and RANKL expression was investigated using a real-time PCR. CD14⁺ monocytes were incubated with RANKL, Th17 cytokines, and M-CSF, with/without IVIg, and OC differentiation was determined by counting tartrate-resistant acid phosphatase-positive multinucleated cells. OC differentiation was investigated after monocytes were cocultured with Th17 cells in the presence of IVIg. Th17 cell differentiation was determined using enzyme-linked immunosorbent assay and flow cytometry after CD4⁺ T cells were cultured with IVIg under Th17 condition. Th17 cytokines stimulated monocytes to express RANKL and IVIg suppressed the Th17 cytokine-induced RANKL expression. OCs were differentiated when pre-OC were cocultured with RANKL or Th17 cytokines and IVIg reduced the osteoclastogenesis. IVIg also decreased osteoclastogenesis when pre-OC were cocultured with Th17 cells. IVIg decreased both Th17 and Th1 cell differentiation while it did not affect Treg cell differentiation. In summary, IVIg inhibited Th17 cytokine-induced RANKL expression and OC differentiation. IVIg reduced osteoclastogenesis when monocytes were cocultured with Th17 cells. IVIg also reduced Th17 polarization. IVIg could be a new therapeutic option for Th17 cell–mediated osteoclastogenesis.
Subject(s)
Humans , Cytokines , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Immunoglobulins , Immunoglobulins, Intravenous , Interleukin-17 , Macrophage Colony-Stimulating Factor , Monocytes , Osteoclasts , RANK Ligand , Real-Time Polymerase Chain Reaction , T-Lymphocytes , T-Lymphocytes, Regulatory , Th1 Cells , Th17 CellsABSTRACT
Mycophenolate mofetil (MMF) is an immunosuppressive agent used to treat severe lupus, including lupus nephritis. Common adverse effects of MMF include gastrointestinal and hematological manifestations; however, cardiac toxicity in association with MMF has not been reported. We present a 21-year-old woman with lupus nephritis who developed ventricular tachycardia 2 hours after an overdose of MMF (34 g). Ventricular bigeminy was documented 12 hours after the MMF overdose. Transthoracic echocardiography showed no evidence of structural heart disease. The ventricular arrhythmia was successfully treated with potassium replacement, hydration, and cholestyramine. This case suggests that an overdose of MMF can induce ventricular tachycardia, and electrocardiogram monitoring is critical to identify this rare cardiac complication of MMF.
Subject(s)
Female , Humans , Young Adult , Arrhythmias, Cardiac , Cardiotoxicity , Cholestyramine Resin , Echocardiography , Electrocardiography , Heart Diseases , Lupus Erythematosus, Systemic , Lupus Nephritis , Mycophenolic Acid , Potassium , Tachycardia, VentricularABSTRACT
Immune checkpoint inhibitors (ICIs) have revolutionized anticancer therapy due to their long-term clinical benefits and immune boosting mechanisms. However, despite their consistent therapeutic effects, the use of ICIs is associated with a spectrum of adverse events due to their autoimmune and auto-inflammatory actions. These adverse events can affect any organ system, including the endocrine, neurologic, gastrointestinal, cardiac, skin, pulmonary, and musculoskeletal systems. Of the immune-related adverse events (irAEs), rheumatic complications are common and appear to be distinct from irAEs in other organs in terms of variability of onset time, capacity for persistence, and relationship with pre-existing autoimmune rheumatologic diseases. In this article, we review the mechanisms of the anti-cancer effects of ICIs, the irAEs of immuno-oncology drugs, and the general recommendations for managing irAEs. In particular, we focus on rheumatologic irAEs and discuss their prevalence, clinical characteristics, and management.
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BACKGROUND/AIMS@#To define standard reference values for musculoskeletal ultrasonography (MSUS) in Korea.@*METHODS@#A total of 251 healthy adults were recruited for this study. Ultrasonography was performed by experienced rheumatologists who had undergone four appropriate training programs in Korea. A General Electric LOGIQ electronic ultrasound device fitted with a 12 MHz linear transducer was employed. Mean values ± standard deviations (SDs) were defined as standard reference values. Intraclass correlation coefficients was employed to evaluate the extent of inter- and intraobserver agreement when MSUS measurements were made.@*RESULTS@#The 251 study participants included 122 males. Mean subject age was 28.6 years. The average bone-to-capsule distance of the right-side second and third metacarpophalangeal (MCP) joints were 0.68 and 0.72 mm respectively, and those of the left-side joints 0.62 and 0.68 mm. The cartilage thicknesses of the right-side second and third MCP joints were 0.55 and 0.55 mm, and those of the left-side joints were 0.55 and 0.56 mm, respectively. The bone-to-capsule distances of the right and left wrists were 0.80 and 0.82 mm. In 12.4% of participants (31/251), the erosion score of the humeral head was 1.71. In the right-side knee joint, mean cartilage thicknesses of the medial and lateral condyles were 1.86 and 2.03 mm in longitudinal scans. High overall interobserver agreement was evident after appropriate training that included instruction on standard MSUS methodology.@*CONCLUSIONS@#We defined standard reference values for MSUS in healthy Korean adults. The reliabilities of interobserver agreements were high after appropriate training program.
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BACKGROUND/AIMS@#Magnetic resonance imaging (MRI) is a sensitive and useful method for the detection of synovitis and joint destruction in rheumatoid arthritis (RA) patients. However, the patterns of MRI-detected bone erosion, bone marrow edema (BME), synovitis, and tenosynovitis have received insufficient attention. Therefore, this study evaluated the patterns of bone erosion, BME, synovitis, and tenosynovitis, and calculated the RA-MRI score (RAMRIS) of patients with RA at the carpal and metacarpophalangeal (MCP) joints using MRI.@*METHODS@#MRI datasets from 43 RA patients were analyzed. All patients had undergone MRI of one wrist. In addition, 36 patients had MCP joint images taken, and three had also received MRI of the contralateral wrist and MCP joints. The MR images were evaluated for bone erosion, BME, and synovitis in consensus by two blinded readers according to the Outcome Measures in Rheumatology Clinical Trials (OMERACT) RAMRIS. The MRI-detected tenosynovitis was evaluated based on Haavardsholm's tenosynovitis score.@*RESULTS@#The capitate, lunate, triquetrum, and hamate bones were the most common sites of erosion and BME and showed the highest RAMRIS erosion and BME scores. Moreover, MRI-detected tenosynovitis was present in 78.3% of all patients with RA, and the extensor compartment 4 and flexor digitorum profundus and superficialis were frequently affected.@*CONCLUSIONS@#This study identified the distribution and prevalence of MRI-detected bone erosion, BME, synovitis, and tenosynovitis of the wrist and MCP joints in RA patients. The patterns of the MRI-detected abnormalities may help to select sites for the application of MRI protocols in clinical trials and practice.
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In the article cited above, there was an error in the title.