The Development and Validation of an AI Diagnostic Model for Sacroiliitis: A Deep-Learning Approach.

PURPOSE: Sacroiliitis refers to the inflammatory condition of the sacroiliac joints, frequently causing lower back pain. It is often associated with systemic conditions. However, its signs on radiographic images can be subtle, which may result in it being overlooked or underdiagnosed. This study aims to utilize artificial intelligence (AI) to create a diagnostic tool for more accurate sacroiliitis detection in radiological images, with the goal of optimizing treatment plans and improving patient outcomes. MATERIALS AND METHOD: The study included 492 patients who visited our hospital. Right sacroiliac joint films were independently evaluated by two musculoskeletal radiologists using the Modified New York criteria (Normal, Grades 1-4). A consensus reading resolved disagreements. The images were preprocessed with Z-score standardization and histogram equalization. The DenseNet121 algorithm, a convolutional neural network with 201 layers, was used for learning and classification. All steps were performed on the DEEP:PHI platform. RESULT: The AI model exhibited high accuracy across different grades: 94.53% (Grade 1), 95.83% (Grade 2), 98.44% (Grade 3), 96.88% (Grade 4), and 96.09% (Normal cases). Sensitivity peaked at Grade 3 and Normal cases (100%), while Grade 4 achieved perfect specificity (100%). PPVs ranged from 82.61% (Grade 1) to 100% (Grade 4), and NPVs peaked at 100% for Grade 3 and Normal cases. The F1 scores ranged from 64.41% (Grade 1) to 95.38% (Grade 3). CONCLUSIONS: The AI diagnostic model showcased a robust performance in detecting and grading sacroiliitis, reflecting its potential to enhance diagnostic accuracy in clinical settings. By facilitating earlier and more accurate diagnoses, this model could substantially impact treatment strategies and patient outcomes.

Inflammation is responsible for systemic bone loss in patients with seropositive rheumatoid arthritis treated with rituximab.

BACKGROUND/AIMS: We investigated the effect of rituximab on systemic bone metabolism in patients with seropositive rheumatoid arthritis (RA). METHODS: Twenty seropositive patients with RA were enrolled and administered one cycle of rituximab. If RA became active for > 6 months after the first rituximab cycle, a second cycle was initiated; otherwise, no additional treatment was administered. Patients were divided into two groups according to the number of rituximab treatment cycles. RESULTS: In patients treated with a second cycle, the total hip bone mineral density (BMD) was clinically low, whereas the serum levels of receptor activator of nuclear factor kappa-B ligand (RANKL) were increased at 12 months. BMD in patients treated with one cycle did not change at 12 months, whereas serum RANKL levels decreased at all time points. DAS28 activity improved in both groups from baseline to 4 months; however, from 4 to 12 months, DAS28 activity worsened in the develgroup with the second cycle but remained stable in the group with one cycle. CONCLUSION: Systemic inflammation, reflected by increased disease activity, may be responsible for the increase in RANKL levels, which causes systemic bone loss in rituximab-treated patients with RA. Although rituximab affects inflammation, it does not seem to alter systemic bone metabolism in RA.

Factors That Influence Sleep Disturbance and the Mediating Effects of Depression on Sleep Disturbance in Patients With Rheumatoid Arthritis.

Little is known about the nature of relationships between sleep disturbance and influencing factors in rheumatoid arthritis. The purpose of this study was to identify factors that influence sleep disturbance and to evaluate mediating effects of depression on sleep disturbance. A nonexperimental, descriptive, correlational study design was adopted. One hundred patients with rheumatoid arthritis were recruited. Inflammatory status and levels of pain, fatigue, functional disability, depression, and sleep disturbance were measured. The factors that directly influenced sleep disturbance were gender, rheumatoid arthritis duration, serum C-reactive protein level, fatigue, and depression. Depression was found to have mediating effects on the relationships between sleep disturbance and arthritis symptoms. Pain, fatigue, and depression were found to have significant direct or indirect impacts on sleep disturbance. Our findings may improve understanding of sleep disturbance and aid the development of effective nursing management strategies for patients with rheumatoid arthritis suffering from sleep disturbance.

Occurrence of human leukocyte antigen B51-related ankylosing spondylitis in a family: Two case reports.

BACKGROUND: Ankylosing spondylitis (AS) is strongly associated with the human leukocyte antigen (HLA) B27 haplotype. In regions where conventional polymerase chain reaction for HLA typing is available for antigens such as HLA B27 or HLA B51, it is common to perform the HLA B27 test for evaluation of AS. While HLA B27-associated clustered occurrences of AS have been reported in families, we report the first case series of HLA B51-related occurrences of AS in a family. CASE SUMMARY: A father and his daughters were diagnosed with AS and did not have the HLA B27 haplotype. Although they were positive for HLA B51, they exhibited no signs of Behçet's disease (BD). Of the five daughters, one had AS, and three, including the daughter with AS, were positive for HLA B51. The two daughters with the HLA B51 haplotype (excluding the daughter with AS) exhibited bilateral grade 1 sacroiliitis, whereas the daughters without the HLA B51 haplotype did not have sacroiliitis. Thus, this Korean family exhibited a strong association with the HLA B51 haplotype and clinical sacroiliitis, irrespective of the symptoms of BD. CONCLUSION: It is advisable to check for HLA B51 positivity in patients with AS/spondyloarthropathy who test negative for HLA B27.

Obesity potentially protects against systemic bone loss in patients with rheumatoid arthritis treated with tumour necrosis factor inhibitors.

OBJECTIVES: We aimed to investigate how systemic bone metabolism was affected after 1 year of treatment with tumour necrosis factor (TNF) inhibitors in rheumatoid arthritis (RA) patients. METHODS: A total of 29 seropositive RA patients not treated for osteoporosis were enrolled and TNF inhibitors were administered for a year. Bone mineral density (BMD) at the lumbar spine, femur neck, and total hip was measured at baseline and 12 months after anti-TNF treatment. Blood samples were collected at baseline and 6 and 12 months after anti-TNF treatment and osteoclasts were cultured on bone slices. Weight was the strongest factor influencing systemic bone loss. Patients were categorised into two groups: obese (body mass index (BMI) ≥25 kg/m2) and non-obese (BMI <25 kg/m2). RESULTS: All patients showed decreased BMD at all sites. The obese group showed relatively little change in BMD, although the non-obese group showed significant decreases in BMD at all sites after 1 year of treatment with TNF inhibitors. Resorption pits created by osteoclasts decreased at 6 months and increased at 12 months in the non-obese group, while the obese group presented with steadily decreasing sizes of resorption pits at all-time points. Levels of receptor activator of nuclear factor kappa B ligand were significantly decreased at 12 months compared to baseline in the obese group, while they were increased in the non-obese group. CONCLUSIONS: One year of treatment with TNF inhibitors failed to halt systemic bone loss in RA patients, but obesity may have protective effects against bone loss.

A Contemporary View of the Diagnosis of Osteoporosis in Patients With Axial Spondyloarthritis.

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that primarily affects the axial joints. Altered bone metabolism associated with chronic inflammation leads to both new bone formation in the spine and increased bone loss. It is known that patients with axSpA have a high prevalence of osteoporosis and fractures. However, there is no consensus on which imaging modality is the most appropriate for diagnosing osteoporosis in axSpA. Bone mineral density measurement using dual-energy X-ray absorptiometry is the primary diagnostic method for osteoporosis, but it has notable limitations in patients with axSpA. This method may lead to the overestimation of bone density in patients with axSpA because they often exhibit abnormal calcification of spinal ligaments or syndesmophytes. Therefore, the method may not provide adequate information about bone microarchitecture. These limitations result in the underdiagnosis of osteoporosis. Recently, new imaging techniques, such as high-resolution peripheral quantitative computed tomography, and trabecular bone score have been introduced for the evaluation of osteoporosis risk in patients with axSpA. In this review, we summarize the current knowledge regarding imaging techniques for diagnosing osteoporosis in patients with axSpA.

Association of Serum Uric Acid with Cardiovascular Disease Risk Scores in Koreans.

As the prevalence of gout and hyperuricemia increases, the comorbidities of gout and hyperuricemia have become a public health burden. In particular, risks of cardiovascular disease (CVD)-related complications are increasing. However, a few guidelines exist for the management of hyperuricemia. This cross-sectional study aimed to investigate the association of serum uric acid with CVD risk in the general population of Korean adults. We examined cross-sectional data from the first and second years of the seventh Korea National Health and Nutrition Examination Survey 2016-2017. Among 16,277 participants, 8781 were analyzed. We estimated the CVD risk using a 10-year CVD risk score prediction formula. There was a significant association of serum uric acid with 10-year CVD risk scores after adjusting for physical activity, body mass index, serum creatinine, and alcohol consumption in both sexes (p < 0.001). In the fitted fractional polynomial model, an approximate U-shaped association between serum uric acid levels and 10-year CVD risk scores was found in men. At the serum uric acid level of 6.9 mg/dL, the CVD risk was lowest. An approximate J-shaped association between serum uric acid levels and 10-year CVD risk scores was found in women. Our study showed that hyperuricemia was associated with an increased CVD risk. Hypouricemia was also associated with an increased CVD risk in men. We, therefore, recommend proper management of uric acid levels in the general population to reduce CVD risks.

Efficacy and safety of tocilizumab in Korean patients with active rheumatoid arthritis.

BACKGROUND/AIMS: To investigate the efficacy and safety of tocilizumab (TCZ) humanized anti-interleukin-6 receptor monoclonal antibody, in Korean patients with active rheumatoid arthritis (RA) refractory to conventional disease modifying anti-rheumatic drugs (DMARDs) including methotrexate (MTX). METHODS: The main study was a 24-week, randomized, double-blind, controlled trial that was followed by a 48-week, open-labeled, extension phase. TCZ (8 mg/kg) or placebo was intravenously administered every 4 weeks. RESULTS: Those treated with TCZ showed more favorable outcomes in terms of 20% according to the American College of Rheumatology response criteria (ACR20) and ACR50 responses, individual parameters of ACR core set, disease activity score in 28 joints (DAS28) remission, and European League Against Rheumatism (EULAR) response at week 24. These improvements were maintained or increased during the extension period. DAS28 remission at week 72 was associated with EULAR good response at week 12. The patients who experienced any adverse event (AE) were more frequent in the TCZ group compared to the placebo group. Most AEs were mild or moderate in intensity, although TCZ therapy had possible AEs including serious infection, abnormal liver function, and atherogenic lipid profile. CONCLUSION: TCZ infusion add-on is highly efficacious and well-tolerated in Korean patients with active RA refractory to conventional DMARDs including MTX. EULAR good response at week 12 could predict DAS28 remission at week 72.

Osteoporosis in Rheumatic Diseases: Anti-rheumatic Drugs and the Skeleton.

Osteoporosis in rheumatic diseases is a very well-known complication. Systemic inflammation results in both generalized and localized bone loss and erosions. Recently, increased knowledge of inflammatory process in rheumatic diseases has resulted in the development of potent inhibitors of the cytokines, the biologic DMARDs. These treatments reduce systemic inflammation and have some effect on the generalized and localized bone loss. Progression of bone erosion was slowed by TNF, IL-6 and IL-1 inhibitors, a JAK inhibitor, a CTLA4 agonist, and rituximab. Effects on bone mineral density varied between the biological DMARDs. Medications that are approved for the treatment of osteoporosis have been evaluated to prevent bone loss in rheumatic disease patients, including denosumab, cathepsin K, bisphosphonates, anti-sclerostin antibodies and parathyroid hormone (hPTH 1-34), and have some efficacy in both the prevention of systemic bone loss and reducing localized bone erosions. This article reviews the effects of biologic DMARDs on bone mass and erosions in patients with rheumatic diseases and trials of anti-osteoporotic medications in animal models and patients with rheumatic diseases.

Efficacy, Safety and Pharmacokinetics of Up to Two Courses of the Rituximab Biosimilar CT-P10 Versus Innovator Rituximab in Patients with Rheumatoid Arthritis: Results up to Week 72 of a Phase I Randomized Controlled Trial.

BACKGROUND: CT-P10 is a biosimilar of innovator rituximab (RTX), a biological therapy used to treat patients with rheumatoid arthritis (RA) who have responded inadequately to anti-tumor necrosis factor agents. OBJECTIVE: Our objective was to compare the clinical profile of CT-P10 versus RTX in patients with RA who received up to two courses of treatment and were followed for up to 72 weeks. METHODS: In this multicenter double-blind phase I study, patients were randomized 2:1 to receive CT-P10 1000 mg or RTX 1000 mg at weeks 0 and 2. Based on disease activity, patients could receive a second course of treatment between weeks 24 and 48. Efficacy endpoints, including mean change from baseline in Disease Activity Score using 28 joints (DAS28), safety, immunogenicity, pharmacokinetics, and pharmacodynamics were evaluated. RESULTS: In total, 154 patients were randomized to CT-P10 or RTX (n = 103 and 51, respectively); 137 (n = 92 and 45) completed the first course of treatment, of whom 83 (n = 60 and 23) were re-treated. Improvements from baseline in all efficacy endpoints were highly similar between the CT-P10 and RTX groups over both treatment courses. At week 24 after the second course, mean change from week 0 of the first course in DAS28 erythrocyte sedimentation rate was -2.47 and -2.04 for CT-P10 and RTX, respectively, (p = 0.1866) and in DAS28 C-reactive protein was -2.32 and -2.00, respectively (p = 0.3268). The proportion of patients positive for antidrug antibodies at week 24 after the second treatment course was 20.0% and 21.7% in the CT-P10 and RTX groups, respectively. The safety profile of CT-P10 was comparable to that of RTX, and pharmacokinetic and pharmacodynamic properties were similar. CONCLUSIONS: In patients with RA, efficacy, safety, and other clinical data were comparable between CT-P10 and RTX after up to two courses of treatment over 72 weeks. (ClinicalTrials.gov identifier NCT01534884).

Efficacy and Safety of Switching from Innovator Rituximab to Biosimilar CT-P10 Compared with Continued Treatment with CT-P10: Results of a 56-Week Open-Label Study in Patients with Rheumatoid Arthritis.

BACKGROUND: CT-P10 is a biosimilar candidate of innovator rituximab (RTX) that demonstrated a comparable clinical profile to RTX in a phase I randomized controlled trial (RCT) in rheumatoid arthritis (RA) (ClinicalTrials.gov identifier: NCT01534884). OBJECTIVE: This open-label extension (OLE) study (NCT01873443) compared the efficacy and safety of CT-P10 in patients with RA who received CT-P10 from the outset (i.e., from the start of the RCT and also in the OLE; 'maintenance group') with those who received RTX during the RCT and switched to CT-P10 during the OLE ('switch group'). METHODS: Patients who completed the RCT were recruited. Based on the Disease Activity Score using 28 joints (DAS28) and predefined safety criteria, patients could receive up to two courses of CT-P10 during the OLE. Efficacy [DAS28 and European League Against Rheumatism (EULAR) response], safety and immunogenicity were assessed. RESULTS: Eighty-seven patients were enrolled; 58 and 29 had previously received CT-P10 or RTX, respectively, in the RCT. Of these, 38 (65.5%) and 20 (69.0%) were treated with CT-P10 in the OLE and therefore comprised the maintenance and switch groups, respectively. The mean change in DAS28-erythrocyte sedimentation rate (ESR) from baseline (week 0 of RCT) at week 24 of the first OLE treatment course in the maintenance and switch groups was -2.7 and -2.4, respectively. The proportion of patients with good/moderate EULAR responses was also comparable between groups. Antidrug antibodies were detected in 13.2 and 15.0% of patients in the maintenance and switch groups, respectively, at week 24 of the first OLE course. CT-P10 treatment was well-tolerated when administered for up to 2 years or after switching from RTX. CONCLUSION: In this study population, comparable efficacy and safety profiles were observed in patients who switched from RTX to CT-P10 and those maintained on CT-P10 throughout treatment.

The effect of anti-TNF treatment on osteoblastogenesis in ankylosing spondylitis: the number of circulating osteoblast-lineage cells in peripheral blood decreased after infliximab therapy in patients with ankylosing spondylitis.

OBJECTIVES: The full effect of anti-TNF therapy on new bone formation is still in debate in spondylitis fields. We sought to obtain circulating osteoblast-lineage cells in peripheral blood from ankylosing spondylitis (AS) patients and healthy control subjects, and to evaluate the effect of before and after anti TNF-α therapy on osteoblastogenesis in patients with AS. METHODS: Sixteen male patients with AS slated for infliximab therapy and 19 controls were recruited. We cultured osteoblast-lineage cells from peripheral blood and measured the optical density of their Alizarin red S staining. We also measured serum P1NP (procollagen type 1 N-terminal propeptide) as an early osteoblast differentiation marker, osteocalcin as a late osteoblast differentiation marker, and inflammatory markers. RESULTS: There were significantly more circulating osteoblast-lineage cells in patients than in controls. The number of circulating osteoblast-lineage cells and optical density of Alizarin red S staining decreased 14 weeks after infliximab therapy (p=0.028); serum level of P1NP decreased, but that of osteocalcin increased (p=0.002 and 0.007, respectively). CONCLUSIONS: Our data reveals that first, the circulating osteoblast-lineage cells are recoverable and increased in AS patients, and also that they decrease after infliximab therapy; second, infliximab therapy resolves early inflammation, but allows mature osteoblast differentiation in late inflammation. The culture of osteoblast-lineage cells in peripheral blood may be a candidate for a new modality with which to study spondylitis and other autoimmune diseases.

A multicentre randomised controlled trial to compare the pharmacokinetics, efficacy and safety of CT-P10 and innovator rituximab in patients with rheumatoid arthritis.

OBJECTIVE: To demonstrate pharmacokinetic equivalence of CT-P10 and innovator rituximab (RTX) in patients with rheumatoid arthritis (RA) with inadequate responses or intolerances to antitumour necrosis factor agents. METHODS: In this randomised phase I trial, patients with active RA were randomly assigned (2:1) to receive 1000 mg CT-P10 or RTX at weeks 0 and 2 (alongside continued methotrexate therapy). Primary endpoints were area under the serum concentration-time curve from time zero to last quantifiable concentration (AUC0-last) and maximum serum concentration after second infusion (Cmax). Additional pharmacokinetic parameters, efficacy, pharmacodynamics, immunogenicity and safety were also assessed. Data are reported up to week 24. RESULTS: 103 patients were assigned to CT-P10 and 51 to RTX. The 90% CIs for the ratio of geometric means (CT-P10/RTX) for both primary endpoints were within the bioequivalence range of 80%-125% (AUC0-last: 97.7% (90% CI 89.2% to 107.0%); Cmax: 97.6% (90% CI 92.0% to 103.5%)). Pharmacodynamics and efficacy were comparable between groups. Antidrug antibodies were detected in 17.6% of patients in each group at week 24. CT-P10 and RTX displayed similar safety profiles. CONCLUSIONS: CT-P10 and RTX demonstrated equivalent pharmacokinetics and comparable efficacy, pharmacodynamics, immunogenicity and safety. TRIAL REGISTRATION NUMBER: NCT01534884.

Efficacy and safety of switching from reference infliximab to CT-P13 compared with maintenance of CT-P13 in ankylosing spondylitis: 102-week data from the PLANETAS extension study.

OBJECTIVES: To investigate the efficacy and safety of switching from infliximab reference product (RP) to its biosimilar or maintaining biosimilar treatment in patients with ankylosing spondylitis (AS). METHODS: This open-label extension study recruited patients with AS who completed a 54-week, randomised controlled study comparing CT-P13 with RP (PLANETAS). CT-P13 (5 mg/kg) was administered intravenously every 8 weeks from week 62 to week 102. Efficacy end points included the proportion of patients achieving Assessment of SpondyloArthritis international Society (ASAS)20. Antidrug antibodies (ADAs) were measured using an electrochemiluminescent method. Data were analysed for patients treated with CT-P13 in the main PLANETAS study and the extension (maintenance group) and those who were switched to CT-P13 during the extension study (switch group). RESULTS: Overall, 174 (82.9%) of 210 patients who completed the first 54 weeks of PLANETAS and agreed to participate in the extension were enrolled. Among these, 88 were maintained on CT-P13 and 86 were switched to CT-P13 from RP. In these maintenance and switch groups, respectively, ASAS20 response rates at week 102 were 80.7% and 76.9%. ASAS40 and ASAS partial remission were also similar between groups. ADA positivity rates were comparable (week 102: 23.3% vs 27.4%). Adverse events led to treatment discontinuation during the extension study in 3 (3.3%) and 4 (4.8%) patients, respectively. CONCLUSIONS: This is the first study to show that switching from RP to its biosimilar CT-P13 is possible without negative effects on safety or efficacy in patients with AS. In the maintenance group, CT-P13 was effective and well tolerated over 2 years of treatment. TRIAL REGISTRATION NUMBER: NCT01571206; Results.

Early effects of tumor necrosis factor inhibition on bone homeostasis after soluble tumor necrosis factor receptor use.

BACKGROUND/AIMS: Our aim was to assess whether short-term treatment with soluble tumor necrosis factor (TNF) receptor affects circulating markers of bone metabolism in rheumatoid arthritis (RA) patients. METHODS: Thirty-three active RA patients, treated with oral disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids for > 6 months, were administered etanercept for 12 weeks. Serum levels of bone metabolism markers were compared among patients treated with DMARDs at baseline and after etanercept treatment, normal controls and naive RA patients not previously treated with DMARDs (both age- and gender-matched). RESULTS: Bone-specific alkaline phosphatase (BSALP) and serum c-telopeptide (CTX)-1 levels were lower in RA patients treated with DMARDs than in DMARD-naive RA patients. After 12 weeks of etanercept treatment, serum CTX-1 and sclerostin levels increased. In patients whose DAS28 improved, the sclerostin level increased from 1.67 ± 2.12 pg/mL at baseline to 2.51 ± 3.03 pg/mL, which was statistically significant (p = 0.021). Increases in sclerostin levels after etanercept treatment were positively correlated with those of serum CTX-1 (r = 0.775), as were those of BSALP (r = 0.755). CONCLUSIONS: RA patients treated with DMARDs showed depressed bone metabolism compared to naive RA patients. Increases in serum CTX-1 and sclerostin levels after short-term etanercept treatment suggest reconstitution of bone metabolism homeostasis.

Prevention of comorbidity and acute attack of gout by uric acid lowering therapy.

The object of this study was to evaluate the effect of uric acid lowering therapy in reducing the new development of comorbidities and the frequency of acute attacks in gout patients. We retrospectively reviewed patients who were diagnosed to have gout with at least 3 yr of follow up. They were divided into 2 groups; 53 patients with mean serum uric acid level (sUA)<6 mg/dL and 147 patients with mean sUA≥6 mg/dL. Comorbidities of gout such as hypertension (HTN), type II diabetes mellitus (DM), chronic kidney disease, cardiovascular disease (CVD) and urolithiasis were compared in each group at baseline and at last follow-up visit. Frequency of acute gout attacks were also compared between the groups. During the mean follow up period of 7.6 yr, the yearly rate of acute attack and the new development of HTN, DM, CVD and urolithiasis was lower in the adequately treated group compared to the inadequately treated group. Tight control of uric acid decreases the incidence of acute gout attacks and comorbidities of gout such as HTN, DM, CVD and urolithiasis.

Digital thermography of the fingers and toes in Raynaud's phenomenon.

The aim of this study was to determine whether skin temperature measurement by digital thermography on hands and feet is useful for diagnosis of Raynaud's phenomenon (RP). Fifty-seven patients with RP (primary RP, n = 33; secondary RP, n = 24) and 146 healthy volunteers were recruited. After acclimation to room temperature for 30 min, thermal imaging of palmar aspect of hands and dorsal aspect of feet were taken. Temperature differences between palm (center) and the coolest finger and temperature differences between foot dorsum (center) and first toe significantly differed between patients and controls. The area under curve analysis showed that temperature difference of the coolest finger (cutoff value: 2.2℃) differentiated RP patients from controls (sensitivity/specificity: 67/60%, respectively). Temperature differences of first toe (cutoff value: 3.11℃) also discriminated RP patients (sensitivity/specificity: about 73/66%, respectively). A combination of thermographic assessment of the coolest finger and first toe was highly effective in men (sensitivity/specificity : about 88/60%, respectively) while thermographic assessment of first toe was solely sufficient for women (sensitivity/specificity: about 74/68%, respectively). Thermographic assessment of the coolest finger and first toe is useful for diagnosing RP. In women, thermography of first toe is highly recommended.