Machine learning models with time-series clinical features to predict radiographic progression in patients with ankylosing spondylitis.

Objective: Ankylosing spondylitis (AS) is chronic inflammatory arthritis causing structural damage and radiographic progression to the spine due to repeated and continuous inflammation over a long period. This study establishes the application of machine learning models to predict radiographic progression in AS patients using time-series data from electronic medical records (EMRs). Methods: EMR data, including baseline characteristics, laboratory findings, drug administration, and modified Stoke AS Spine Score (mSASSS), were collected from 1,123 AS patients between January 2001 and December 2018 at a single center at the time of first (T1), second (T2), and third (T3) visits. The radiographic progression of the (n+1)th visit (Pn+1=(mSASSSn+1-mSASSSn)/(Tn+1-Tn)≥1 unit per year) was predicted using follow-up visit datasets from T1 to Tn. We used three machine learning methods (logistic regression with the least absolute shrinkage and selection operation, random forest, and extreme gradient boosting algorithms) with three-fold cross-validation. Results: The random forest model using the T1 EMR dataset best predicted the radiographic progression P2 among the machine learning models tested with a mean accuracy and area under the curves of 73.73% and 0.79, respectively. Among the T1 variables, the most important variables for predicting radiographic progression were in the order of total mSASSS, age, and alkaline phosphatase. Conclusion: Prognosis predictive models using time-series data showed reasonable performance with clinical features of the first visit dataset when predicting radiographic progression.

The relationship between long-term use of nonsteroidal anti-inflammatory drugs and kidney function in patients with ankylosing spondylitis.

Objective: Although nonsteroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment for ankylosing spondylitis (AS), their effect on kidney function remains unclear. This longitudinal study investigated the correlation between long-term NSAID use and kidney function in patients with AS using electronic medical records. Methods: The electronic medical records of 1,280 patients with AS collected from a single center between January 2001 and December 2018 were reviewed. The Assessment of Spondyloarthritis International Society (ASAS) NSAID Intake Score was used to determine the cumulative dose of all NSAIDs prescribed for a different time intervals. Each ASAS NSAID Intake Score was obtained for intervals of 6 months, 1 year, 2 years, 3 years, 5 years, and 10 years. The correlation between the ASAS NSAID Intake Score and final estimated glomerular filtration rate (eGFR) for each interval was investigated. Results: The mean ASAS Intake Scores for 6-month, 1-year, 2-year, 3-year, 5-year, and 10-year intervals were 55.30, 49.28, 44.84, 44.14, 44.61, and 41.17, respectively. At each interval, the pearson correlation coefficients were -0.018 (95% CI -0.031 to -0.006, p=0.004), -0.021 (95% CI -0.039 to -0.004, p=0.018), -0.045 (95% CI -0.071 to -0.019, p=0.001), -0.069 (95% CI -0.102 to -0.037, p<0.001), -0.070 (95% CI -0.114 to -0.026, p=0.002), -0.019 (95% CI -0.099 to 0.062, p=0.645), respectively. There was a very weak negative relationship between ASAS Intake Score and eGFR at each interval. Conclusion: Long-term NSAID use did not correlate with kidney function based on real-world data in patients with AS.

Radiographic involvement of cervical facet joints in ankylosing spondylitis: a longitudinal analysis in correlation with vertebral body lesions.

BACKGROUND: The inability to assess structural changes in facet joints is a limitation of established radiographic scoring systems for ankylosing spondylitis (AS). We compared radiographic evidence of ankylosis in cervical facet joints and cervical vertebral bodies in patients with AS. METHODS: We analysed longitudinal data collected from 1106 AS patients and assessed 4984 spinal radiographs obtained up to 16 years of follow-up. Comparisons between cervical facet joints and cervical vertebral bodies focused on the presence of ankylosis, which was defined by at least one facet joint exhibiting complete ankylosis (according to the method of de Vlam) or at least one vertebral body with a bridging syndesmophyte (according to the modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS]). Ankylosis was assessed over time using spinal radiographs collected during follow-up periods stratified in 4-year increments. RESULTS: Patients with cervical facet joint ankylosis had higher cervical mSASSS, sacroiliitis grades, and inflammatory markers, with more prevalent hip involvement and uveitis. Overall, the numbers of spinal radiographs indicating ankylosis were comparable between cervical facet joints (17.8%) and cervical vertebral bodies (16.8%), and they usually presented together (13.5%). We observed similar proportions of radiographs with ankylosis only in cervical facet joints (4.3%) and cervical vertebral bodies (3.3%). As damage progressed, configurations with both cervical facet joint ankylosis and bridging syndesmophytes became more predominant with longer follow-up times, while configurations with cervical facet joint ankylosis only or bridging syndesmophytes only were less frequently observed. CONCLUSIONS: Evidence of cervical facet joint ankylosis appears as often as bridging syndesmophytes on routine AS spinal radiographs. Presence of cervical facet joint ankylosis should be considered because it may have a higher disease burden.

Association between changes in serum alkaline phosphatase levels and radiographic progression in ankylosing spondylitis.

This retrospective study evaluated the electronic medical records of patients with ankylosing spondylitis (AS) (January 2001-December 2018) to determine the relationship between serum alkaline phosphatase (ALP) levels and radiographic changes over time. Longitudinal data, including serum ALP levels, were imputed by linear interpolation at 3-month intervals. Among the serum ALP levels calculated for 8 years prior to modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) measurement, those having the highest beta coefficient with the mSASSS were selected in the correlation between ALP and longitudinal mSASSS. Linear mixed models with the selected serum ALP levels, mSASSS, and clinical variables were investigated. We included 1122 patients (mean follow-up, 8.20 [standard deviation: 2.85] years). The serum ALP level from 5 years and 3 months prior showed the highest beta coefficient with the mSASSS. In the linear mixed model, the serum ALP level at 5 years and 3 months before radiographic changes was significantly associated with the mSASSS (ß = 0.021, 95% confidence interval: 0.017-0.025, p < 0.001). Serum ALP levels measured approximately 5 years before may be a surrogate marker for predicting spinal radiographic changes. Long-term prospective clinical and experimental studies of > 5 years are required for biomarker discovery or therapeutic research on AS radiographic progression.

The impact of smoking status on radiographic progression in patients with ankylosing spondylitis on anti-tumor necrosis factor treatment.

Background: Ankylosing spondylitis (AS) is characterized by back pain which can lead to spinal ankylosis. Anti-tumor necrosis factor (TNF) dramatically alleviates symptoms, but spinal damage can still be progressive even during anti-TNF treatment. Smoking is a one of well-known risk factors for structural damage in AS. However, it has not been confirmed that smoking can affect radiographic progression even during anti-TNF treatment. Objective: To investigate factors associated with radiographic progression during anti-TNF treatment with a focus on smoking status which is known as one of poor prognostic factors for AS. Materials and methods: We conducted a retrospective cohort study of AS patients who began the first-line anti-TNF treatment between 2001 and 2018 according to availability of smoking data. All enrolled patients were observed until the last visit, the first-line anti-TNF discontinuation, or December 2019. Radiographic damage was assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). The mSASSS progression rate (units/year) was calculated using the baseline mSASSS, the final mSASSS during observation period, and the duration between them. Univariable and multivariable logistic regression analyses were performed to identify associated factors of mSASSS progression rate > 1 unit/year. Results: Among 459 AS patients, 185 (40.3%) patients were never smokers, 62 (13.5%) were ex-smokers and 212 (46.2%) were current smokers at baseline. Ex- and current smokers had higher mSASSS progression rates than never smokers [never smoker 0.1 (0.0-0.7), ex-smoker 0.6 (0.0-1.5), and current smoker 0.6 (0.0-1.5) units/year, P < 0.001]. In the multivariable logistic analysis, current smoking [adjusted odds ratio (OR) 1.69, 95% CI 1.01-2.82, P = 0.047] and higher baseline mSASSS [adjusted OR 1.03, 95% CI 1.01-1.04, P < 0.001] were associated with a mSASSS progression rate > 1 unit/year. Conclusion: Current smoking is a modifiable risk factor for radiographic progression in patients with AS on anti-TNF treatment. Quitting smoking should be strongly recommended.

Prediction of radiographic progression pattern in patients with ankylosing spondylitis using group-based trajectory modeling and decision trees.

Objective: This study aimed to identify trajectories of radiographic progression of the spine over time and use them, along with associated clinical factors, to develop a prediction model for patients with ankylosing spondylitis (AS). Methods: Data from the medical records of patients diagnosed with AS in a single center were extracted between 2001 and 2018. Modified Stoke Ankylosing Spondylitis Spinal Scores (mSASSS) were estimated from cervical and lumbar radiographs. Group-based trajectory modeling classified patients into trajectory subgroups using longitudinal mSASSS data. In multivariate analysis, significant clinical factors associated with trajectories were selected and used to develop a decision tree for prediction of radiographic progression. The most appropriate group for each patient was then predicted using decision tree analysis. Results: We identified three trajectory classes: class 1 had a uniformly increasing slope of mSASSS, class 2 showed sustained low mSASSS, and class 3 showed little change in the slope of mSASSS but highest mSASSS from time of diagnosis to after progression. In multivariate analysis for predictive factors, female sex, younger age at diagnosis, lack of eye involvement, presence of peripheral joint involvement, and low baseline erythrocyte sedimentation rate (log) were significantly associated with class 2. Class 3 was significantly associated with male sex, older age at diagnosis, presence of ocular involvement, and lack of peripheral joint involvement when compared with class 1. Six clinical factors from multivariate analysis were used for the decision tree for classifying patients into three trajectories of radiographic progression. Conclusion: We identified three patterns of radiographic progression over time and developed a decision tree based on clinical factors to classify patients according to their trajectories of radiographic progression. Clinically, this model holds promise for predicting prognosis in patients with AS.

Differences in trajectory of disease activity according to biologic and targeted synthetic disease-modifying anti-rheumatic drug treatment in patients with rheumatoid arthritis.

BACKGROUND: The purpose of this study was to stratify patients with rheumatoid arthritis (RA) according to the trend of disease activity by trajectory-based clustering and to identify contributing factors for treatment response to biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs) according to trajectory groups. METHODS: We analyzed the data from a nationwide RA cohort from the Korean College of Rheumatology Biologics and Targeted Therapy registry. Patients treated with second-line biologic and targeted synthetic DMARDs were included. Trajectory modeling for clustering was used to group the disease activity trend. The contributing factors using the machine learning model of SHAP (SHapley Additive exPlanations) values for each trajectory were investigated. RESULTS: The trends in the disease activity of 688 RA patients were clustered into 4 groups: rapid decrease and stable disease activity (group 1, n = 319), rapid decrease followed by an increase (group 2, n = 36), slow and continued decrease (group 3, n = 290), and no decrease in disease activity (group 4, n = 43). SHAP plots indicated that the most important features of group 2 compared to group 1 were the baseline erythrocyte sedimentation rate (ESR), prednisolone dose, and disease activity score with 28-joint assessment (DAS28) (SHAP value 0.308, 0.157, and 0.103, respectively). The most important features of group 3 compared to group 1 were the baseline ESR, DAS28, and estimated glomerular filtration rate (eGFR) (SHAP value 0.175, 0.164, 0.042, respectively). The most important features of group 4 compared to group 1 were the baseline DAS28, ESR, and blood urea nitrogen (BUN) (SHAP value 0.387, 0.153, 0.144, respectively). CONCLUSIONS: The trajectory-based approach was useful for clustering the treatment response of biologic and targeted synthetic DMARDs in patients with RA. In addition, baseline DAS28, ESR, prednisolone dose, eGFR, and BUN were important contributing factors for 4-year trajectories.

A pilot study on deep learning-based grading of corners of vertebral bodies for assessment of radiographic progression in patients with ankylosing spondylitis.

Background: Radiographs are widely used to evaluate radiographic progression with modified stoke ankylosing spondylitis spinal score (mSASSS). Objective: This pilot study aimed to develop a deep learning model for grading the corners of the cervical and lumbar vertebral bodies for computer-aided detection of mSASSS in patients with ankylosing spondylitis (AS). Methods: Digital radiographic examination of the spine was performed using Discovery XR656 (GE Healthcare) and Digital Diagnost (Philips). The disk points were detected between the bodies using a key-point detection deep learning model from the image obtained in DICOM (digital imaging and communications in medicine) format from the cervical and lumbar spinal radiographs. After cropping the vertebral regions around the disk point, the lower and upper corners of the vertebral bodies were classified as grade 3 (total bony bridges) or grades 0, 1, or 2 (non-bridges). We trained a convolutional neural network model to predict the grades in the lower and upper corners of the vertebral bodies. The performance of the model was evaluated in a validation set, which was separate from the training set. Results: Among 1280 patients with AS for whom mSASSS data were available, 5,083 cervical and 5245 lumbar lateral radiographs were reviewed. The total number of corners where mSASSS was measured in the cervical and lumbar vertebrae, including the upper and lower corners, was 119,414. Among them, the number of corners in the training and validation sets was 110,088 and 9326, respectively. The mean accuracy, sensitivity, and specificity for mSASSS scoring in one corner of the vertebral body were 0.91604, 0.80288, and 0.94244, respectively. Conclusion: A high-performance deep learning model for grading the corners of the vertebral bodies was developed for the first time. This model must be improved and further validated to develop a computer-aided tool for assessing mSASSS in the future.

Relationship Between Inflammation and Radiographic Progression in Patients With Ankylosing Spondylitis Attaining a BASDAI of Less Than 4 During Tumor Necrosis Factor Inhibitor Treatment.

OBJECTIVE: To determine the relationship between inflammation and radiographic progression over time in patients with ankylosing spondylitis (AS) attaining a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) of < 4 during tumor necrosis factor inhibitor (TNFi) treatment. METHODS: Medical records data of patients with AS with BASDAI scores of < 4 during TNFi treatment were analyzed at 6-month intervals from January 2001 to December 2018. To determine the relationship between the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and C-reactive protein (CRP) over time, we fitted linear mixed models with mSASSS as the response variable, baseline mSASSS and the cumulative sum of CRP with different lag times (6, 12, 18, 24, 30, and 36 months) as fixed effects, and patients as random effects. Associations between mSASSS and the cumulative sum of CRP, or the lag times with the highest beta coefficients, were further investigated with linear mixed models that included additional clinical variables. RESULTS: A total of 2956 intervals were obtained from 333 patients. Among different lag times, the cumulative sum of log CRP in the previous 18 to 36 months associated with mSASSS showed significant beta coefficients. In the final linear mixed model, the cumulative sum of log CRP in the previous 24 months was significantly associated with mSASSS at 24 months (ß 0.04, 95% CI 0.01-0.07, P = 0.004). CONCLUSION: Remnant inflammation correlates with radiographic progression, even in patients attaining a BASDAI of < 4 during TNFi treatment. CRP is a surrogate marker for radiographic progression despite clinical improvement with TNFi treatment.

Age-stratified trends in the progression of spinal radiographic damage in patients with ankylosing spondylitis: a longitudinal study.

Objective: The objective of this study was to investigate spinal radiographic progression in specific age ranges of ankylosing spondylitis (AS) patients. Methods: Longitudinal data for 1125 AS patients at a single hospital from 2000 to 2018 were retrospectively reviewed. Radiographic intervals were obtained from patients with consecutive spinal radiographs. The radiographic progression rate was defined as the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) change per year within each interval. Using generalized estimating equations (GEEs), estimated marginal means were calculated for the mSASSS progression rate across age groups after adjusting for potential confounders. Results: We obtained 4016 radiographic intervals and stratified them into five groups based on patient age at the interval start: <20 (n = 122); 20-29 (n = 1124); 30-39 (n = 1690); 40-49 (n = 794); and ⩾50 years (n = 286). The mean (SD) mSASSS progression rate for all the intervals was 0.8 (1.9). The GEE-estimated mean mSASSS progression rate increased with age, peaking in the 30-39 age group with a value of 1.15 [95% confidence interval (CI) 1.03, 1.27], and decreased slightly thereafter. In the presence of risk factors, rapid progression occurred at earlier ages: the GEE-estimated mean mSASSS progression rate in those with elevated C-reactive protein levels and preexisting syndesmophytes was 2.82 (95% CI 1.93, 3.71) in the 20-29 age group. Conclusion: Spinal structural damage in AS seems to progress most rapidly when patients are age 30-39 years. An awareness of the trends in radiographic progression with advancing age could improve understanding of the natural course of AS.

Early control of C-reactive protein levels with non-biologics is associated with slow radiographic progression in radiographic axial spondyloarthritis.

AIM: Predicting radiographic progression is vital for assessing the prognosis of patients with radiographic axial spondyloarthritis, and C-reactive protein (CRP) may be a valuable biomarker for this purpose. This study aimed to investigate the relationship between changes in the CRP level and spinal radiographic progression in patients with radiographic axial spondyloarthritis who were initially treated with non-biologics. METHODS: Patients with radiographic axial spondyloarthritis who were followed up for 18 years at a single center and initially treated with nonsteroidal anti-inflammatory drugs and/or conventional disease-modifying antirheumatic drugs for 3 months were included. Patients with a CRP level of <0.8 mg/dL or 50% of the baseline CRP at 3 months were assigned to the controlled CRP group (n = 351), and the remaining patients were assigned to the uncontrolled CRP group (n = 452). A generalized estimating equation was used to analyze the differences in the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) between the 2 groups. RESULTS: The increase in the mSASSS was slower in the controlled CRP group than in the uncontrolled CRP group (interaction term ß = -.499, 95% confidence interval -0.699 to -0.300). CONCLUSION: Controlled CRP achieved in response to initial treatment with non-biologic agents for 3 months was significantly associated with a slower rate of spinal radiographic change in patients with radiographic axial spondyloarthritis. The CRP level at 3 months after initial non-biologic treatment is a good predictor of radiographic progression.

Reliability and Quality of Korean YouTube Videos for Education Regarding Gout.

BACKGROUND: YouTube has become an increasingly popular educational tool and an important source of healthcare information. We investigated the reliability and quality of the information in Korean-language YouTube videos about gout. METHODS: We performed a comprehensive electronic search on April 2, 2021, using the following keywords-"gout," "acute gout," "gouty arthritis," "gout treatment," and "gout attack"-and identified 140 videos in the Korean language. Two rheumatologists then categorized the videos into three groups: "useful," "misleading," and "personal experience." Reliability was determined using a five-item questionnaire modified from the DISCERN validation tool, and overall quality scores were based on the Global Quality Scale (GQS). RESULTS: Among the 140 videos identified, 105 (75.0%), 29 (20.7%), and 6 (4.3%) were categorized as "useful," "misleading," and "personal experience," respectively. Most videos in the "useful" group were created by rheumatologists (70.5%). The mean DISCERN and GQS scores in the "useful" group (3.3 ± 1.0 and 3.8 ± 0.7) were higher than those in the "misleading" (0.9 ± 1.0 and 1.9 ± 0.6) and "personal experience" groups (0.8 ± 1.2 and 2.0 ± 0.8) (P < 0.001 for both the DISCERN and GQS tools). CONCLUSION: Approximately 75% of YouTube videos that contain educational material regarding gout were useful; however, we observed some inaccuracies in the medical information provided. Healthcare professionals should closely monitor media content and actively participate in the development of videos that provide accurate medical information.

Use of Quantitative Vertebral Bone Marrow Fat Fraction to Assess Disease Activity and Chronicity in Patients with Ankylosing Spondylitis.

OBJECTIVE: We quantitatively measured the fat fraction (FF) in the vertebrae of patients with ankylosing spondylitis (AS) using magnetic resonance imaging (MRI) and investigated the role of FF as an indicator of both active inflammation and chronicity. MATERIALS AND METHODS: A total of 52 patients with AS who underwent spinal MRI were retrospectively evaluated. The FF values of the anterosuperior and anteroinferior corners of the bone marrow in the L1-S1 spine were assessed using the modified Dixon technique. AS activity was measured using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), AS Disease Activity Score (ASDAS), and serum inflammatory marker levels. AS disease chronicity was assessed by AS disease duration and the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Univariable and multivariable regression analyses were conducted to investigate the correlation between FF and other clinical characteristics. RESULTS: The mean FF ± standard deviation of the total lumbar spine was 43.0% ± 11.3%. At univariable analysis, spinal FF showed significant negative correlation with BASDAI (ß = -0.474, p = 0.002) and ASDAS with C-reactive protein (ASDAS-CRP; ß = -0.478, p = 0.002) and a significant positive correlation with AS disease duration (ß = 0.440, p = 0.001). After adjusting for patient age, sex, and total mSASSS score, spinal FF remained significantly negatively correlated with BASDAI (ß = -0.543, p < 0.001), ASDAS-CRP (ß = -0.568, p < 0.001), and ASDAS with erythrocyte sedimentation rate (ß = -0.533, p = 0.001). Spinal FF was significantly lower in patients with very high disease activity (ASDAS-CRP > 3.5) than in those with only high disease activity (2.1 ≤ ASDAS-CRP ≤ 3.5) (p = 0.010). CONCLUSION: Spinal FF may help assess both AS disease activity and chronicity.

Machine learning model for identifying important clinical features for predicting remission in patients with rheumatoid arthritis treated with biologics.

BACKGROUND: We developed a model to predict remissions in patients treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs) and to identify important clinical features associated with remission using explainable artificial intelligence (XAI). METHODS: We gathered the follow-up data of 1204 patients treated with bDMARDs (etanercept, adalimumab, golimumab, infliximab, abatacept, and tocilizumab) from the Korean College of Rheumatology Biologics and Targeted Therapy Registry. Remission was predicted at 1-year follow-up using baseline clinical data obtained at the time of enrollment. Machine learning methods (e.g., lasso, ridge, support vector machine, random forest, and XGBoost) were used for the predictions. The Shapley additive explanation (SHAP) value was used for interpretability of the predictions. RESULTS: The ranges for accuracy and area under the receiver operating characteristic of the newly developed machine learning model for predicting remission were 52.8-72.9% and 0.511-0.694, respectively. The Shapley plot in XAI showed that the impacts of the variables on predicting remission differed for each bDMARD. The most important features were age for adalimumab, rheumatoid factor for etanercept, erythrocyte sedimentation rate for infliximab and golimumab, disease duration for abatacept, and C-reactive protein for tocilizumab, with mean SHAP values of - 0.250, - 0.234, - 0.514, - 0.227, - 0.804, and 0.135, respectively. CONCLUSIONS: Our proposed machine learning model successfully identified clinical features that were predictive of remission in each of the bDMARDs. This approach may be useful for improving treatment outcomes by identifying clinical information related to remissions in patients with rheumatoid arthritis.

Effect of combined pulmonary fibrosis and emphysema on patients with connective tissue diseases and systemic sclerosis: a systematic review and meta-analysis.

BACKGROUND: This study aimed to analyze the literature systematically to determine the clinical characteristics and prognosis of patients with connective tissue disease (CTD) with combined pulmonary fibrosis and emphysema (CPFE) compared to those of patients with CTD-interstitial lung disease (CTD-ILD) without emphysema. METHODS: We searched MEDLINE, EMBASE, Cochrane Library, and KoreaMed for relevant articles published before July 2019. Studies meeting all the following criteria were included: (1) original research studies evaluating the effect of CPFE on CTD, (2) studies that compared patients with CTD-CPFE to those with CTD-ILD without emphysema, and (3) studies providing data on physical capacity, pulmonary function, or death in patients with CTD. Clinical characteristics of patients with CTD-CPFE were compared with those of patients with CTD-ILD without emphysema, and the influence of CPFE on physical capacity, pulmonary function, and death was analyzed. RESULTS: Six studies between 2013 and 2019 were included. Two hundred ninety-nine (29.5%) and 715 (70.5%) patients had CTD-CPFE and CTD-ILD without emphysema, respectively. Regarding the type of CTD, 711 (68.3%) patients had systemic sclerosis, 263 (25.3%) rheumatoid arthritis, and 67 (6.4%) other CTDs. Patients with CTD-CPFE had a higher frequency of pulmonary hypertension and pulmonary fibrosis > 20% of the total lung volume, higher ratio of the forced vital capacity to the diffusion capacity of the lung for carbon monoxide (DLCO), lower arterial oxygen pressure at rest, and lower DLCO compared to those in patients with CTD-ILD without emphysema. In addition, more deaths occurred among those with CTD-CPFE (odds ratio, 2.95; 95% confidence interval, 1.75-4.96). CONCLUSION: CTD-CPFE is associated with worse physical and pulmonary function and more deaths compared to those in CTD-ILD without emphysema. These findings indicate the need for increased awareness and close monitoring of patients with CTD-CPFE.

Gender differences in factors associated with low quality of life and depression in Korean patients with ankylosing spondylitis.

PURPOSE: To identify predictors of low health-related quality of life (HRQoL) and depression in ankylosing spondylitis (AS) patients with a focus on gender differences. METHODS: We conducted a cross-sectional cohort study. Both AS-related clinical data and contextual factors were obtained. HRQoL and depressive mood were assessed by EuroQol-5 dimension (EQ-5D) and the Center for Epidemiological Studies Depression Scale (CES-D), respectively. Gender-stratified multivariable logistic regression analyses were performed. RESULTS: Among 211 patients, 161 were males. Males had similar disease activity and higher radiographic damage compared with females. There was no significant difference in EQ-5D index score between genders. CES-D score was higher in females. Higher ASDAS-C-reactive protein (CRP) was associated with low HRQoL in both males (Odds ratio [OR] 4.25, 95% confidence interval [CI] 2.42-7.46) and females (OR 2.94, 95% CI 1.02-8.48). Being employed was associated with decreased possibility of having low HRQoL in males (OR 0.39, 95% CI 0.16-0.95). Regarding depression, higher ASDAS-CRP (OR 1.87, 95% CI 1.03-3.40), current smoking (OR 2.98, 95% CI 1.09-8.15), and being employed (OR 0.17, 95% CI 0.06-0.46) were associated with depression in males. For females, living with a partner was related to depression (OR 0.08, 95% CI 0.01-0.93). CONCLUSION: AS patients with high disease activity are likely to be suffering from low HRQoL. Both disease-related factors and contextual factors were associated with depression, and predictors showed some differences between genders. Awareness of gender differences in comprehensive assessment can lead us to better personalized management in AS patients.

Low BASDAI score alone is not a good predictor of anti-tumor necrosis factor treatment efficacy in ankylosing spondylitis: a retrospective cohort study.

BACKGROUND: The purpose of this study was to determine the prevalence of high disease activity as measured using the Ankylosing Spondylitis Disease Activity Score (ASDAS) in ankylosing spondylitis (AS) patients who nonetheless have low Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores after anti-tumor necrosis factor (TNF) treatment. Its clinical impact on anti-TNF survival was also investigated. METHODS: We conducted a single-centre retrospective cohort study of AS patients having low BASDAI scores (< 4) and available ASDAS-C-reactive protein (CRP) data after 3 months of first-line anti-TNF treatment. Patients were grouped into high-ASDAS (≥ 2.1) and low-ASDAS (< 2.1) groups according to the ASDAS-CRP after 3 months of anti-TNF treatment. Their characteristics were compared. And survival analyses were carried out using Kaplan-Meier curves and log-rank test with the event being discontinuation of anti-TNF treatment due to lack/loss of efficacy. RESULTS: Among 116 AS patients with low BASDAI scores after 3 months of anti-TNF treatment, 38.8% were grouped into the high-ASDAS group. The high-ASDAS group tended to have greater disease activity after 9 months of treatment (BASDAI 2.9 ± 1.1 vs. 2.3 ± 1.4, p=0.007; ASDAS-CRP 1.8 ± 0.6 vs. 1.5 ± 0.7, p=0.079; proportion of high ASDAS-CRP 27.8% vs. 13.8%, p=0.094) and greater risk of discontinuing anti-TNF treatment due to lack/loss of efficacy than the low-ASDAS group (p=0.011). CONCLUSIONS: A relatively high proportion of AS patients with low BASDAI scores had high ASDAS-CRP. These low-BASDAI/high-ASDAS-CRP patients also had a greater risk for discontinuation of anti-TNF treatment due to low/lack of efficacy than the low-ASDAS group. The use of the ASDAS-CRP alone or in addition to the BASDAI may improve the assessment of AS patients treated with anti-TNF agents.

Dose Reduction of Tumor Necrosis Factor Inhibitor and its Effect on Medical Costs for Patients with Ankylosing Spondylitis.

INTRODUCTION: Tumor necrosis factor inhibitors (TNFis) may be administered at a reduced dose to patients with ankylosing spondylitis (AS) for various reasons. However, in practice, there is insufficient evidence of how the dose reduction of TNFi is implemented and the amount of medical costs it reduces. In this study, we investigated treatment patterns among patients with AS who were administered various TNFis. The effect on medical costs related to AS was also investigated using Korea's insurance claims database. METHODS: From the insurance claims database of the Health Insurance Review & Assessment Service in South Korea, patients with AS newly treated with TNFis (etanercept, adalimumab, golimumab, and infliximab) between July 1, 2013, and June 30, 2016, were enrolled. Patients treated with the TNFis were followed up for 2 years. Treatment patterns (continuation and discontinuation of TNFi) and dose reduction (< 50% of recommended dose) in patients who continued treatment were analyzed and compared among the TNFi groups using the Chi-square test. Healthcare costs between the dose reduction and maintenance groups were compared using general linear modeling. RESULTS: Of 1352 patients, 764 (56.51%) continued using TNFis for 2 years, and 17.8% of these were administered reduced doses. TNFi dose reduction was the most frequent in 36 (24.83%) patients using etanercept, followed by those using adalimumab (21.97%), golimumab (11.70%), and infliximab (11.98%) (p = 0.0028). For each TNFi group, the total healthcare cost significantly decreased, that is, by 24.85% for adalimumab, 31.80% for etanercept, 26.34% for golimumab, and 35.52% for infliximab (p < 0.0001). CONCLUSIONS: TNFi dose reduction was identified in 17.8% of the patients with AS, and the patterns were different for each TNFi. Additionally, the dose reductions significantly reduced the medical costs associated with AS, that is, from 24.85 to 35.52% of the total medical expenditure.