Real-world incidences and risk factors of immune-related adverse events in patients treated with immune checkpoint inhibitors: A nationwide retrospective cohort study.

Immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) are rare but fatal, requiring systemic steroid use. Therefore, to examine the outcomes, incidence, timing, and risk factors of ICI-associated steroid-requiring severe irAEs, we conducted a nationwide, retrospective, cohort study utilizing the Korean Health Insurance and Review Assessment database. We identified 357,010 patients with lung cancer, bladder cancer, or skin melanoma, eligible for ICI reimbursement in Korea between January 2012 to June 2020. Steroid-requiring severe irAEs following ICI treatment or treatment-emergent AEs following cytotoxic chemotherapy were defined as moderate- or high-dose steroid administration for over 2 consecutive days, along with corresponding ICD-10 codes indicating affected organ systems. The ICI-exposed group (N = 10,118) was compared to a matched cohort of 55,436 ICI-unexposed patients treated with cytotoxic chemotherapy. Incidences of acute severe irAEs requiring moderate- and high-dose steroids were higher in the ICI-exposed group (1.95% and 6.42%, respectively). The ICI-exposed group also had a higher risk of developing delayed severe irAEs requiring moderate- and high-dose steroid use (3.89% and 7.39%). Male sex, high comorbidity index, or previously diagnosed autoimmune diseases were associated with an increased risk of severe irAEs. Notably, 27.4-38.8% of the patients experienced recurrent severe irAEs after re-challenge with ICIs following moderate- or high-dose steroid use, with the severity matching the initial episode. Steroid-requiring severe irAEs were significantly more prevalent among patients exposed to ICIs than among those treated with chemotherapy in acute and delayed periods.

Sex-specific disparities in disease activity scores among patients with axial spondyloarthritis and their implications for evaluating the response to tumor necrosis factor alpha inhibitor therapy.

BACKGROUND: We aimed to investigate whether there are sex differences in disease activity measures among patients with axial spondyloarthritis (axSpA) and to determine any potential impact on the assessment of treatment responses to tumor necrosis factor alpha inhibitors (TNFi). METHODS: Using the Korean College of Rheumatology Biologics and Targeted Therapy (KOBIO) registry data, we compared sex differences in changes in the Bath Ankylosing Spondylitis Disease Activity Score (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) levels at baseline and one year after TNFi initiation in patients with axSpA. RESULTS: This study included 1,753 patients with axSpA who started or changed TNFi, of whom 1,343 (76.6%) were male. At baseline, the mean BASDAI and ASDAS scores of all patients were 5.98 and 3.6, respectively. The BASDAI changes between baseline and the one-year follow-up were independently associated with sex (𝛽 = 0.343, p = 0.011), whereas ASDAS was not (𝛽 = 0.079, p = 0.235). When judging the effect of TNFi at one-year of treatment, male patients were more likely to be assessed as effective by the BASDAI-based criterion (ΔBASDAI ≥ 50% or ≥ 2; OR 1.700, 95% CI 1.200-2.406), while the ASDAS-based criterion (ΔASDAS ≥ 1.1) showed no significant difference between sexes (OR 0.993, 95% CI 0.678-1.455), after adjusting for other baseline characteristics. CONCLUSIONS: The changes in disease activity before and after TNFi use were significantly different between sexes when measured by BASDAI, but not ASDAS. TNFi treatment effects may be interpreted differently between sexes depending on the disease activity measure used.

Second-line chemoimmunotherapy with nivolumab and paclitaxel in immune-related biomarker-enriched advanced gastric cancer: a multicenter phase Ib/II study.

BACKGROUND: We conducted a trial to evaluate the efficacy and safety of nivolumab and paclitaxel as second-line therapy for immune-related biomarker-enriched advanced gastric cancer (AGC). METHODS: This open-label, single-arm, phase Ib/II study was a part of multi-institutional, biomarker-integrated umbrella study conducted in Korea. In phase Ib, patients received nivolumab (3 mg/kg) on Days 1 and 15 and paclitaxel (dose level 1, 70 mg/m2 or dose level 2, 80 mg/m2) on Days 1, 8, 15 every four weeks. In phase II, patients with Epstein-Barr virus-related, deficient mismatch repair or programmed cell death-ligand-1-positive AGC were enrolled. The primary endpoints were recommended phase II dose (RP2D, phase Ib) and progression-free survival (PFS, phase II). Secondary endpoints included objective response rate (ORR), overall survival (OS), safety, and exploratory biomarker analysis. RESULTS: Dose level 2 was selected as RP2D. In phase II, 48 patients were enrolled. The median PFS and OS were 3.9 and 11.2 months, respectively. The ORR was 23.3%, and the median response duration was 16.7 months. Grade 3 or higher treatment-related adverse events, mainly neutropenia, occurred in 20 patients (41.7%). Targeted sequencing revealed that patients with RTK/RAS pathway alterations or the HLA-A02 supertype had better survival. Patients with elevated baseline interleukin-1 receptor antagonist levels had worse survival. CONCLUSIONS: Although the study did not meet its primary end point, nivolumab and paclitaxel for AGC demonstrated a durable response with manageable toxicity profiles. Genomic analysis or plasma cytokine analysis may provide information for the selection of patients who would benefit more from immunotherapy combined with chemotherapy.

Women with Metabolic Syndrome and Unhealthy Lifestyle Factors Are at a Higher Risk for Hyperuricemia.

Hyperuricemia (HUA) has become a significant medical concern due to its complications and links to metabolic syndrome (MetS) and cardiovascular disease (CVD), which result in increased mortality. The pathogenic processes associated with unhealthy behaviors, MetS, and HUA can be cooperative and potentially synergistic in the activation of risk factors. Recent research has shown sex-based differences in the relationship between HUA and its associated risk factors. This study aimed to investigate these differences, particularly in the context of MetS and CVD risk factors and unhealthy lifestyles. We also aimed to evaluate the joint effects of these factors based on sex. We conducted a cross-sectional study using nationally representative survey data from the Korean National Health and Nutritional Examination Survey 2016-2018. We performed multivariable logistic regression analysis, calculating adjusted odds ratios (ORs) with their 95% confidence intervals (CIs). We also conducted subgroup analyses based on sex and the presence of MetS with or without unhealthy lifestyle factors (tobacco use, alcohol intake). We found sex-based differences in the relationships between HUA and MetS, CVD risk factors, and lifestyle behaviors. Our major finding was a significant association between MetS and HUA in both men and women, regardless of alcohol consumption and smoking status, and this association was stronger in women. We also observed a synergistic effect of MetS and lifestyle factors on the risk of HUA, particularly in women, in whom the risk of HUA increased up to four times compared to the reference group. A sex-based clinical strategy for HUA is necessary to reduce related complications and their socio-economic burden.

Performances of machine learning algorithms in discriminating sacroiliitis features on MRI: a systematic review.

OBJECTIVES: Summarise the evidence of the performance of the machine learning algorithm in discriminating sacroiliitis features on MRI and compare it with the accuracy of human physicians. METHODS: MEDLINE, EMBASE, CIHNAL, Web of Science, IEEE, American College of Rheumatology and European Alliance of Associations for Rheumatology abstract archives were searched for studies published between 2008 and 4 June 2023. Two authors independently screened and extracted the variables, and the results are presented using tables and forest plots. RESULTS: Ten studies were selected from 2381. Over half of the studies used deep learning models, using Assessment of Spondyloarthritis International Society sacroiliitis criteria as the ground truth, and manually extracted the regions of interest. All studies reported the area under the curve as a performance index, ranging from 0.76 to 0.99. Sensitivity and specificity were the second-most commonly reported indices, with sensitivity ranging from 0.56 to 1.00 and specificity ranging from 0.67 to 1.00; these results are comparable to a radiologist's sensitivity of 0.67-1.00 and specificity of 0.78-1.00 in the same cohort. More than half of the studies showed a high risk of bias in the analysis domain of quality appraisal owing to the small sample size or overfitting issues. CONCLUSION: The performance of machine learning algorithms in discriminating sacroiliitis features on MRI varied owing to the high heterogeneity between studies and the small sample sizes, overfitting, and under-reporting issues of individual studies. Further well-designed and transparent studies are required.

Artificial intelligence for the detection of sacroiliitis on magnetic resonance imaging in patients with axial spondyloarthritis.

Background: Magnetic resonance imaging (MRI) is important for the early detection of axial spondyloarthritis (axSpA). We developed an artificial intelligence (AI) model for detecting sacroiliitis in patients with axSpA using MRI. Methods: This study included MRI examinations of patients who underwent semi-coronal MRI scans of the sacroiliac joints owing to chronic back pain with short tau inversion recovery (STIR) sequences between January 2010 and December 2021. Sacroiliitis was defined as a positive MRI finding according to the ASAS classification criteria for axSpA. We developed a two-stage framework. First, the Faster R-CNN network extracted regions of interest (ROIs) to localize the sacroiliac joints. Maximum intensity projection (MIP) of three consecutive slices was used to mimic the reading of two adjacent slices. Second, the VGG-19 network determined the presence of sacroiliitis in localized ROIs. We augmented the positive dataset six-fold. The sacroiliitis classification performance was measured using the sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). The prediction models were evaluated using three-round three-fold cross-validation. Results: A total of 296 participants with 4,746 MRI slices were included in the study. Sacroiliitis was identified in 864 MRI slices of 119 participants. The mean sensitivity, specificity, and AUROC for the detection of sacroiliitis were 0.725 (95% CI, 0.705-0.745), 0.936 (95% CI, 0.924-0.947), and 0.830 (95%CI, 0.792-0.868), respectively, at the image level and 0.947 (95% CI, 0.912-0.982), 0.691 (95% CI, 0.603-0.779), and 0.816 (95% CI, 0.776-0.856), respectively, at the patient level. In the original model, without using MIP and dataset augmentation, the mean sensitivity, specificity, and AUROC were 0.517 (95% CI, 0.493-0.780), 0.944 (95% CI, 0.933-0.955), and 0.731 (95% CI, 0.681-0.780), respectively, at the image level and 0.806 (95% CI, 0.729-0.883), 0.617 (95% CI, 0.523-0.711), and 0.711 (95% CI, 0.660-0.763), respectively, at the patient level. The performance was improved by MIP techniques and data augmentation. Conclusion: An AI model was developed for the detection of sacroiliitis using MRI, compatible with the ASAS criteria for axSpA, with the potential to aid MRI application in a wider clinical setting.

Altered Risk of Incident Gout According to Changes in Metabolic Syndrome Status: A Nationwide, Population-Based Cohort Study of 1.29 Million Young Men.

OBJECTIVE: Few data are available on whether changes in metabolic syndrome affect incident gout. This study was undertaken to assess associations between metabolic syndrome status and incident gout, as well as changes in the clinical characteristics of metabolic syndrome and incident gout, in a cohort of young men. METHODS: This nationwide, population-based cohort study included 20-39-year-old men who participated in serial health check-ups. The outcome, incident gout, was defined according to the claims database diagnostic code for gout. Associations among changes in metabolic syndrome status and incident gout were analyzed using Cox proportional hazards models. RESULTS: Among 1,293,166 individuals, 18,473 were diagnosed as having gout (incidence rate 3.36 per 1,000 person-years). Subjects who had chronic metabolic syndrome (defined as metabolic syndrome at all 3 health check-ups) had a nearly 4-fold higher risk of incident gout compared to subjects who did not have metabolic syndrome at any of the 3 health check-ups (adjusted hazard ratio [HRadj ] 3.82 [95% confidence interval (95% CI) 3.67-3.98]). Development of metabolic syndrome more than doubled the risk of incident gout (HRadj 2.31 [95% CI 2.20-2.43]). Conversely, recovery from metabolic syndrome reduced the risk of incident gout by nearly half (HRadj 0.52 [95% CI 0.49-0.56]). Among metabolic syndrome components, changes in elevated triglycerides (development of elevated triglycerides, HRadj 1.74 [95% CI 1.66-1.81]; recovery from elevated triglycerides, HRadj 0.56 [95% CI 0.54-0.59]) and abdominal obesity (development of abdominal obesity, HRadj 1.94 [95% CI 1.85-2.03]; recovery from abdominal obesity, HRadj 0.69 [95% CI 0.64-0.74]) showed the greatest association with altered risk of incident gout. Associations between changes in the status and clinical characteristics of metabolic syndrome and incident gout were more pronounced in subjects ages 20-29 years compared to those ages 30-39 years, and in subjects who were underweight or who had a normal weight. CONCLUSION: Changes in the status and clinical characteristics of metabolic syndrome were associated with altered risk of incident gout. These results suggest that metabolic syndrome is a modifiable risk factor for gout.

Increased risk of incident gout in young men with metabolic syndrome: A nationwide population-based cohort study of 3.5 million men.

Background: To date, few studies have focused on risk factors for gout in young people, and large-scale studies on the relationship between metabolic syndrome (MetS) and gout are lacking. We aimed to investigate the association between gout and MetS in a large nationwide population-based cohort of young men who participated in national health examination. Materials and methods: Cohort included men aged 20-39 years who participated in a health check-up in 2009-2012. A total of 3,569,104 subjects was included in the study, excluding those who had a previous diagnosis of gout or had renal impairment. The outcome was the occurrence of gout, which was defined using the diagnosis code of gout in the claims database. Cox proportional hazard model was used to evaluate the association between MetS and incident gout. Results: Mean follow-up duration was 7.35 ± 1.24 years and the incidence rate of gout was 3.36 per 1,000 person-years. The risk of gout in subjects with MetS was 2.4-fold higher than subjects without MetS. Among the components of MetS, hypertriglyceridemia and abdominal obesity showed the greatest association with gout. As the number of MetS components increased, the risk of gout increased. The association between gout and MetS was more pronounced in relatively young subjects and in low- or normal-weight subjects. Conclusion: Metabolic syndrome is an important risk factor for the gout in young men. In particular, the association between MetS and gout was greater in young and non-obese men. Management of MetS in young men will be important for future gout prevention.

Increased risk of malignancy in patients with Takayasu's arteritis: a population-based cohort study in Korea.

This study aimed to evaluate the relative risk of malignancy in patients with Takayasu's arteritis compared to that in the general population. This retrospective nationwide cohort study used data from the Korean Health Insurance Review and Assessment Service database. All newly diagnosed patients with Takayasu's arteritis were identified between January 2009 and December 2019. They were observed until the diagnosis of malignancy, death, or end of the observational period, December 2020. The standardized incidence ratios (SIRs) of the overall and site-specific malignancies were estimated and compared with the incidence of cancer in the general population retrieved from the National Cancer Registry. We identified 1449 newly diagnosed patients with Takayasu's arteritis during the observational period (9196 person-years). A total of 74, 66, and 8 patients had overall, solid, and hematologic malignancies, respectively. The risks of overall [SIR, 1.62; 95% confidence interval (CI) 1.27-2.03], solid (SIR, 1.51; 95% CI 1.17-1.92), and hematologic (SIR, 4.05; 95% CI 1.75-7.98) malignancies were increased compared to those in the general population. In solid malignancies, breast (SIR, 2.07; 95% CI 1.16-3.42) and ovarian (SIR, 4.45; 95% CI 1.21-11.39) cancers had an increased risk. In hematologic malignancies, the risk of myelodysplasia increased (SIR, 18.02; 95% CI 3.72-52.66). Immunosuppressive agent use was not associated with malignancy. There was no specific period when cancer more frequently occurred. An increased risk of malignancy was observed in patients with Takayasu's arteritis compared to that in the general population in this large-scale nationwide population study of Korean health insurance data.

Associations between Cardiovascular Outcomes and Rheumatoid Arthritis: A Nationwide Population-Based Cohort Study.

Despite a growing burden posed by cardiovascular disease (CVD) in rheumatoid arthritis (RA) patients, large-scale studies on the association between the characteristics of RA patients and CVD risks and studies adjusted for various confounding factors are lacking. In this large-scale nationwide cohort study, we aimed to investigate the association between CVD risk and RA and factors that may increase CVD risk using a dataset provided by the Korean National Health Insurance Service (NHIS). We enrolled 136,469 patients with RA who participated in national health examinations within two years of RA diagnosis between 2010 and 2017 and non-RA controls matched by age and sex (n = 682,345). The outcome was the occurrence of myocardial infarction (MI) or stroke. MI was defined as one hospitalization or two outpatient visits with ICD-10-CM codes I21 or I22. Stroke was defined as one hospitalization with ICD-10-CM codes I63 or I64 and a claim for brain imaging (CT or MRI). The Cox proportional hazard model and Kaplan-Meier curve were used for analysis. The mean follow-up duration was 4.7 years, and the incidence rate of CVD was higher in the RA group than the control group (MI: 3.20 vs. 2.08; stroke: 2.84 vs. 2.33 per 1000 person-years). The risk of MI and stroke was about 50% and 20% higher, respectively, in RA patients. The association between RA and CVD was prominent in females after adjusting for confounding variables. The association between RA and risk of MI was significant in individuals without DM. Therefore, appropriate screening for CVD is important in all RA patients including females and younger patients.

Cardiovascular risk associated with allopurinol or benzbromarone treatment in patients with gout.

Background: In previous studies, cardiovascular (CV) risk was increased in patients with gout. The effects of uric acid-lowering therapy on CV risk in gout patients have been investigated in numerous studies; however, allopurinol and benzbromarone have rarely been compared. Objectives: To compare CV risk based on allopurinol and benzbromarone treatment in Korean gout patients. Design: A nationwide population-based retrospective cohort study. Methods: We used South Korea database of the Health Insurance Review and Assessment (HIRA) service to identify gout patients ⩾18 years of age who newly started allopurinol or benzbromarone between 2009 and 2015. The primary outcome of the study was the occurrence of a composite CV endpoint, which included coronary revascularization, hospitalization due to myocardial infarction, ischemic stroke, and transient ischemic attack. Cox proportional hazard regression analysis and Kaplan-Meier curves were used for analysis. Results: The study included 257,097 allopurinol initiators and 7868 benzbromarone initiators. Compared with allopurinol initiators, the adjusted hazard ratio (aHR) of the composite CV endpoint of benzbromarone initiators was 1.01 [95% confidence interval (CI): 0.83-1.21], which was not significantly different. The results did not change even when 1:3 propensity score matching was performed for baseline characteristics. In subgroup analysis of high-risk patients with CV disease, significant difference was not observed between allopurinol and benzbromarone initiators. Conclusion: In this study, significant difference was not found in CV risk between allopurinol and benzbromarone initiators. In the high-CV-risk group, the incidence of CV events did not differ between allopurinol and benzbromarone initiators.

Clinical application of bone turnover markers in treating osteoporotic vertebral compression fractures and their role in predicting fracture progression.

This study aimed to investigate whether changes in the bone turnover markers (BTMs) during teriparatide therapy for osteoporotic vertebral compression fractures could reflect therapeutic effects by analyzing the relationship between clinical and radiological features and BTMs. A total of 33 patients with 51 osteoporotic vertebral compression fracture segments were included. Plain radiographs and BTM levels were evaluated at the pretreatment and at 3 months after teriparatide treatment. Based on serial vertebral compression ratio analysis, the progression of fracture was defined as a vertebral compression ratio decrease of ≥10%, relative to the pretreatment values. All segments were divided into 2 groups: the "maintain" group with 32 (62.7%) segments and the "progression" group with 19 (37.3%) segments. After the teriparatide treatment, serum osteocalcin and serum C-terminal telopeptide of type I collagen levels (P = .028 and .008, respectively), and change amounts of them were significantly larger, increasing (P = .001) in the progression group. The vitamin D (25OH-D) levels were significantly lower (P = .038) in the progression group; however, the relative changes in the 25OH-D levels between the 2 groups, before and after the treatment, were not significantly different (P = .077). The parathyroid hormone (PTH) levels were reduced by the teriparatide treatment in both groups, while the decrease in PTH concentration after the treatment was significantly more pronounced in the progression group (P = .006). Significant increase in the osteocalcin and serum C-terminal telopeptide of type I collagen levels and a simultaneous decrease in the PTH levels during the teriparatide treatment suggest that clinicians should assume the progression of fracture.

Metabolic discrimination of synovial fluid between rheumatoid arthritis and osteoarthritis using gas chromatography/time-of-flight mass spectrometry.

INTRODUCTION: Rheumatoid arthritis (RA) and osteoarthritis (OA) are clinicopathologically different. OBJECTIVES: We aimed to assess the feasibility of metabolomics in differentiating the metabolite profiles of synovial fluid between RA and OA using gas chromatography/time-of-flight mass spectrometry. METHODS: We first compared the global metabolomic changes in the synovial fluid of 19 patients with RA and OA. Partial least squares-discriminant, hierarchical clustering, and univariate analyses were performed to distinguish metabolites of RA and OA. These findings were then validated using synovial fluid samples from another set of 15 patients with RA and OA. RESULTS: We identified 121 metabolites in the synovial fluid of the first 19 samples. The score plot of PLS-DA showed a clear separation between RA and OA. Twenty-eight crucial metabolites, including hypoxanthine, xanthine, adenosine, citrulline, histidine, and tryptophan, were identified to be capable of distinguishing RA metabolism from that of OA; these were found to be associated with purine and amino acid metabolism. CONCLUSION: Our results demonstrated that metabolite profiling of synovial fluid could clearly discriminate between RA and OA, suggesting that metabolomics may be a feasible tool to assist in the diagnosis and advance the comprehension of pathological processes for diseases.

Clinical characteristics and radiographic outcomes of vascular Behçet's disease involving the aorta or its major branches.

OBJECTIVE: To describe the clinical characteristics and radiographic outcomes of vascular Behçet's disease (BD) involving the aorta or its major branches. METHODS: This retrospective cohort study was performed in patients with vascular BD involving the aorta or its major branches. All included patients underwent computed tomography angiography (CTA) at least two times with a 2- to 5-year interval. Radiographic progression was defined as newly developed and/or aggravated (> 20%) characteristic features on CTA. RESULTS: The cohort included 22 patients with BD with a median interval of 3.65 years between the initial and follow-up CTA. Five patients (22.7%) showed radiographic progression. Patients with radiographic progression had a longer disease duration at baseline than those without (6.67 vs. 0.26 years, p = 0.028). Of all patients, 21 (95.5%) had vascular aneurysms/pseudoaneurysms and 11 (50.0%) had thrombosis. The most frequently involved artery with aneurysmal change was the abdominal aorta (8/21, 38.1%), followed by the iliac arteries (5/21, 23.8%). In the case of thrombosis, the most frequently involved arteries were the femoral (4/11, 36.4%) and iliac (4/11, 36.4%) arteries. The characteristics and locations of vascular involvement did not significantly differ according to the radiographic outcome. CONCLUSIONS: A considerable proportion of patients with BD with arterial involvement showed radiographic progression within 2-5 years. Patients with radiographic progression had a longer disease duration at baseline. The most common form of arterial involvement of BD was aneurysmal change, followed by thrombus formation. KEY POINTS: • This study evaluated for the first time the radiographic outcomes of 22 patients with Behçet's disease involving the aorta or its major branches. • A considerable proportion of patients (5/22, 22.7%) showed radiographic progression. • Patients with radiographic progression had a longer disease duration at baseline than their counterparts; however, no other clinical factors were significantly different. • The most frequent form of vascular involvement was pseudoaneurysm followed by thrombosis.

Association between female reproductive factors and gout: a nationwide population-based cohort study of 1 million postmenopausal women.

BACKGROUND: Previous studies have shown that the incidence and risk factors of gout differs according to sex. However, little research has been done on the association between reproductive factors and gout. We conducted an analysis of a large nationwide population-based cohort of postmenopausal women to determine whether there is an association between reproductive factors and the incidence of gout. METHODS: A total of 1,076,378 postmenopausal women aged 40-69 years who participated in national health screenings in 2009 were included in the study. The outcome was the occurrence of incident gout, which was defined using the ICD-10 code of gout (M10) in the claim database. Cox proportional hazard models were used for the analyses and stratified analyses according to body mass index (BMI) and the presence/absence of chronic kidney disease (CKD) were performed. RESULTS: The mean follow-up duration was 8.1 years, and incident cases of gout were 64,052 (incidence rate 7.31 per 1000 person-years). Later menarche, earlier menopause, and a shorter reproductive span were associated with a high risk of gout. No association between parity and gout incidence was observed. Use of oral contraceptives (OC) and hormone replacement therapy (HRT) were associated with an increased risk of gout. The association between reproductive factors and gout was not statistical significant in the high BMI group. The effects of OC and HRT usage on gout were not significant in the CKD group. CONCLUSION: Shorter exposure to endogenous estrogen was associated with a high risk of gout. Conversely, exposure to exogenous estrogen such as OC and HRT was associated with an increased risk of gout.

A cluster analysis of patients with axial spondyloarthritis using tumour necrosis factor alpha inhibitors based on clinical characteristics.

BACKGROUND: This study aimed to classify the distinct group of patients with axial spondyloarthritis (SpA) on tumour necrosis factor alpha inhibitors (TNFi) according to the baseline characteristics using a clustering algorithm. METHODS: The clinical characteristics and demographic data of patients with axial SpA included in the Korean College of Rheumatology Biologics and Targeted Therapy registry were investigated. The patterns of disease manifestations were examined using divisive hierarchical cluster analysis. After clustering, we compared the clinical characteristics of patients and the drug survival of TNFi between the classified groups. RESULTS: A total of 1042 patients were analysed. The cluster analysis classified patients into two groups: axial group predominantly showing isolated axial manifestations (n = 828) and extra-axial group more frequently showing extra-axial symptoms (n = 214). Almost all extra-axial symptoms (peripheral arthritis, enthesitis, uveitis, and psoriasis) were more frequently observed in the extra-axial group than in the axial group. Moreover, patients in the extra-axial group had shorter disease duration, later disease onset, and higher disease activity than those in the axial group. The disease activity was comparable between the two groups after 1 year of treatment with TNFi. Interestingly, the extra-axial group had a lower drug survival with TNFi than the axial group (p = 0.001). CONCLUSIONS: Cluster analysis of patients with axial SpA using TNFi classified two distinct clinical phenotypes. These clusters had different TNFi drug survival, clinical characteristics, and disease activity.

Machine learning-based prediction model for responses of bDMARDs in patients with rheumatoid arthritis and ankylosing spondylitis.

BACKGROUND: Few studies on rheumatoid arthritis (RA) have generated machine learning models to predict biologic disease-modifying antirheumatic drugs (bDMARDs) responses; however, these studies included insufficient analysis on important features. Moreover, machine learning is yet to be used to predict bDMARD responses in ankylosing spondylitis (AS). Thus, in this study, machine learning was used to predict such responses in RA and AS patients. METHODS: Data were retrieved from the Korean College of Rheumatology Biologics therapy (KOBIO) registry. The number of RA and AS patients in the training dataset were 625 and 611, respectively. We prepared independent test datasets that did not participate in any process of generating machine learning models. Baseline clinical characteristics were used as input features. Responders were defined as those who met the ACR 20% improvement response criteria (ACR20) and ASAS 20% improvement response criteria (ASAS20) in RA and AS, respectively, at the first follow-up. Multiple machine learning methods, including random forest (RF-method), were used to generate models to predict bDMARD responses, and we compared them with the logistic regression model. RESULTS: The RF-method model had superior prediction performance to logistic regression model (accuracy: 0.726 [95% confidence interval (CI): 0.725-0.730] vs. 0.689 [0.606-0.717], area under curve (AUC) of the receiver operating characteristic curve (ROC) 0.638 [0.576-0.658] vs. 0.565 [0.493-0.605], F1 score 0.841 [0.837-0.843] vs. 0.803 [0.732-0.828], AUC of the precision-recall curve 0.808 [0.763-0.829] vs. 0.754 [0.714-0.789]) with independent test datasets in patients with RA. However, machine learning and logistic regression exhibited similar prediction performance in AS patients. Furthermore, the patient self-reporting scales, which are patient global assessment of disease activity (PtGA) in RA and Bath Ankylosing Spondylitis Functional Index (BASFI) in AS, were revealed as the most important features in both diseases. CONCLUSIONS: RF-method exhibited superior prediction performance for responses of bDMARDs to a conventional statistical method, i.e., logistic regression, in RA patients. In contrast, despite the comparable size of the dataset, machine learning did not outperform in AS patients. The most important features of both diseases, according to feature importance analysis were patient self-reporting scales.

Risks and benefits of timely screw removal after thoracolumbar spine fractures treated with non-fusion technique.

BACKGROUND: Percutaneous-short segment screw fixation (SSSF) without bone fusion has proven to be a safe and effective modality for thoracolumbar spine fractures (TLSFs). When fracture consolidation is confirmed, pedicle screws are no longer essential, but clear indications for screw removal following fracture consolidation have not been established. METHODS: In total, we enrolled 31 patients with TLSFs who underwent screw removal following treatment using percutaneous-SSSF without fusion. Plain radiographs, taken at different intervals, measured local kyphosis using Cobb' angle (CA), vertebra body height (VBH), and the segmental motion angle (SMA). A visual analogue scale (VAS) and the Oswestry disability index (ODI) were applied pre-screw removal and at the last follow-up. RESULTS: The overall mean CA deteriorated by 1.58° (p < 0.05) and the overall mean VBH decreased by 0.52 mm (p = 0.001). SMA preservation was achieved in 18 patients (58.1%) and kyphotic recurrence occurred in 4 patients (12.9%). SMA preservation was statistically significant in patients who underwent screw removal within 12 months following the primary operation (p = 0.002). Kyphotic recurrence occurred in patients with a CA ≥ 20° at injury (p < 0.001) with a median interval of 16.5 months after screw removal. No patients reported worsening pain or an increased ODI score after screw removal. CONCLUSION: Screw removal within 12 months can be recommended for restoration of SMA with improvement in clinical outcomes. Although, TLSFs with CA ≥ 20° at the time of injury can help to predict kyphotic recurrence after screw removal, the clinical outcomes are less relevant.

Factors associated with radiographic progression in patients with Takayasu's arteritis.

OBJECTIVES: To identify the factors related to radiographic progression in patients with Takayasu's arteritis (TAK). METHODS: A retrospective cohort study was conducted among patients with TAK who underwent computed tomography angiography (CTA) at least twice in a 2-5-year interval. Radiographic progression was defined as newly developed and/or aggravated (more than 20%) characteristic CTA findings. Correlation analysis was performed using a multivariate Cox regression model. RESULTS: The cohort included 153 TAK patients with a mean CTA interval of 3.53 years, and 24 (15.7%) showed radiographic progression. Those with progression showed higher acute-phase reactant levels (erythrocyte sedimentation rate [ESR], 26.06 vs. 35.72 mm/h, p=0.040; C-reactive protein [CRP], 0.45 vs. 1.13 mg/dL, p<0.001), were younger at the initial CTA (43.70 vs. 31.81 years, p<0.001), and were more likely to be receiving immunosuppressants (14 [10.9%] vs. 7 [29.2%] patients, p=0.038). Multivariate Cox regression analysis revealed age at the initial CTA (hazard ratio [HR]=0.945, confidence interval [CI]=0.898-0.995, p=0.030) and area under the curve (AUC) of CRP levels (HR=2.126, CI=1.046-4.319, p=0.037) as significant factors for radiographic progression. In a subgroup of patients with high CRP levels, 30.4% (14/24) showed progression; only age at the initial CTA was significantly different (37.03 vs. 27.10 years, p=0.012) between those with and without progression. CONCLUSIONS: Higher CRP levels and younger age were risk factors of radiographic progression in patients with TAK. In the high CRP group, younger patients are more prone to progression and may need aggressive anti-inflammatory treatment.

Machine learning to predict early TNF inhibitor users in patients with ankylosing spondylitis.

We aim to generate an artificial neural network (ANN) model to predict early TNF inhibitor users in patients with ankylosing spondylitis. The baseline demographic and laboratory data of patients who visited Samsung Medical Center rheumatology clinic from Dec. 2003 to Sep. 2018 were analyzed. Patients were divided into two groups: early-TNF and non-early-TNF users. Machine learning models were formulated to predict the early-TNF users using the baseline data. Feature importance analysis was performed to delineate significant baseline characteristics. The numbers of early-TNF and non-early-TNF users were 90 and 505, respectively. The performance of the ANN model, based on the area under curve (AUC) for a receiver operating characteristic curve (ROC) of 0.783, was superior to logistic regression, support vector machine, random forest, and XGBoost models (for an ROC curve of 0.719, 0.699, 0.761, and 0.713, respectively) in predicting early-TNF users. Feature importance analysis revealed CRP and ESR as the top significant baseline characteristics for predicting early-TNF users. Our model displayed superior performance in predicting early-TNF users compared with logistic regression and other machine learning models. Machine learning can be a vital tool in predicting treatment response in various rheumatologic diseases.