Cost-Effectiveness of Biosimilars vs Leflunomide in Patients With Rheumatoid Arthritis.

Importance: Among patients with rheumatoid arthritis (RA) who had an inadequate response to methotrexate, a treatment sequence initiated with biosimilar disease-modifying antirheumatic drugs (DMARDs) provides better clinical efficacy compared with conventional synthetic DMARDs recommended by current treatment guidelines; but its cost-effectiveness evidence remains unclear. Objective: To evaluate the cost-effectiveness of the treatment sequence initiated with biosimilar DMARDs after failure with methotrexate vs leflunomide and inform formulary listing decisions. Design, Setting, and Participants: This economic evaluation's cost-effectiveness analysis was performed at a Hong Kong public institution using the Markov disease transition model to simulate the lifetime disease progression and cost for patients with RA, using monetary value in 2022. Scenario and sensitivity analyses were performed to test the internal validity of the modeling conclusion. Participants included patients diagnosed with RA from 2000 to 2021 who were retrieved retrospectively from local electronic medical records to generate model input parameters. Statistical analysis was performed from January 2023 to March 2024. Interventions: The model assesses 3 competing treatment sequences initiated with biosimilar infliximab (CT-P13), biosimilar adalimumab (ABP-501), and leflunomide; all used in combination with methotrexate. Main Outcomes and Measures: Lifetime health care cost and quality-adjusted life-years (QALYs) of the simulated cohort. Results: In total, 25 099 patients with RA were identified (mean [SD] age, 56 [17] years; 19 469 [72.7%] women). In the base-case analysis, the lifetime health care cost and QALYs for the treatment sequence initiated with leflunomide were US $154 632 and 14.82 QALYs, respectively; for biosimilar infliximab, they were US $152 326 and 15.35 QALYs, respectively; and for biosimilar adalimumab, they were US $145 419 and 15.55 QALYs, respectively. Both biosimilar sequences presented lower costs and greater QALYs than the leflunomide sequence. In the deterministic sensitivity analysis, the incremental cost-effectiveness ratio (US$/QALY) comparing biosimilar infliximab sequence vs leflunomide sequence and biosimilar adalimumab sequence vs leflunomide sequence ranged from -15 797 to -8615 and -9088 to 10 238, respectively, all below the predefined willingness-to-pay threshold (US $48 555/QALY gain). In the probabilistic sensitivity analysis, the probability of treatment sequence initiated with leflunomide, biosimilar infliximab, and biosmilar adalimumab being cost-effective out of 10 000 iterations was 0%, 9%, and 91%, respectively. Conclusions and Relevance: In this economic evaluation study, the treatment sequences initiated with biosimilar DMARDs were cost-effective compared with the treatment sequence initiated with leflunomide in managing patients with RA who experienced failure with the initial methotrexate treatment. These results suggest the need to update clinical treatment guidelines for initiating biosimilars immediately after the failure of methotrexate for patients with RA.

MRI for axial SpA: Diagnosis, disease activity assessment, and recent advances.

Magnetic resonance imaging (MRI) is a sensitive imaging modality to detect early inflammatory changes in axial spondyloarthritis (SpA). Over a decade has passed since the inclusion of MRI assessment in the 2009 Assessment of SpondyloArthritis International Society (ASAS) classification criteria for axial SpA. Evidence and clinical experience of MRI in axial SpA have accumulated rapidly since. This has led to a better understanding of the clinical utility of MRI in early diagnosis, disease activity assessment, and monitoring of treatment response in axial SpA. Furthermore, technological advancements have paved the way for the development of novel MRI sequences for the quantification of inflammation and image optimization. The field of artificial intelligence has also been explored to aid medical imaging interpretation, including MRI in axial SpA. This review serves to provide an update on the latest understanding of the evolving roles of MRI in axial SpA.

Deep Learning Algorithm of the SPARCC Scoring System in SI Joint MRI.

BACKGROUND: The Spondyloarthritis Research Consortium of Canada (SPARCC) scoring system is a sacroiliitis grading system. PURPOSE: To develop a deep learning-based pipeline for grading sacroiliitis using the SPARCC scoring system. STUDY TYPE: Prospective. POPULATION: The study included 389 participants (42.2-year-old, 44.6% female, 317/35/37 for training/validation/testing). A pretrained algorithm was used to differentiate image with/without sacroiliitis. FIELD STRENGTH/SEQUENCE: 3-T, short tau inversion recovery (STIR) sequence, fast spine echo. ASSESSMENT: The regions of interest as ground truth for models' training were identified by a rheumatologist (HYC, 10-year-experience) and a radiologist (KHL, 6-year-experience) using the Assessment of Spondyloarthritis International Society definition of MRI sacroiliitis independently. Another radiologist (YYL, 4.5-year-experience) solved the discrepancies. The bone marrow edema (BME) and sacroiliac region models were for segmentation. Frangi-filter detected vessels used as intense reference. Deep learning pipeline scored using SPARCC scoring system evaluating presence and features of BMEs. A rheumatologist (SCWC, 6-year-experience) and a radiologist (VWHL, 14-year-experience) scored using the SPARCC scoring system once. The radiologist (YYL) scored twice with 5-day interval. STATISTICAL TESTS: Independent samples t-tests and Chi-squared tests were used. Interobserver and intraobserver reliability by intraclass correlation coefficient (ICC) and Pearson coefficient evaluated consistency between readers and the deep learning pipeline. We evaluated the performance using sensitivity, accuracy, positive predictive value, and Dice coefficient. A P-value <0.05 was considered statistically significant. RESULTS: The ICC and the Pearson coefficient between the SPARCC scores from three readers and the deep learning pipeline were 0.83 and 0.86, respectively. The sensitivity in identifying BME and accuracy of identifying SI joints and blood vessels was 0.83, 0.90, and 0.88, respectively. The dice coefficients were 0.82 (sacrum) and 0.80 (ilium). DATA CONCLUSION: The high consistency with human readers indicated that deep learning pipeline may provide a SPARCC-informed deep learning approach for scoring of STIR images in spondyloarthritis. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

A deep neural network for MRI spinal inflammation in axial spondyloarthritis.

OBJECTIVE: To develop a deep neural network for the detection of inflammatory spine in short tau inversion recovery (STIR) sequence of magnetic resonance imaging (MRI) on patients with axial spondyloarthritis (axSpA). METHODS: A total 330 patients with axSpA were recruited. STIR MRI of the whole spine and clinical data were obtained. Regions of interests (ROIs) were drawn outlining the active inflammatory lesion consisting of bone marrow edema (BME). Spinal inflammation was defined by the presence of an active inflammatory lesion on the STIR sequence. The 'fake-color' images were constructed. Images from 270 and 60 patients were randomly separated into the training/validation and testing sets, respectively. Deep neural network was developed using attention UNet. The neural network performance was compared to the image interpretation by a radiologist blinded to the ground truth. RESULTS: Active inflammatory lesions were identified in 2891 MR images and were absent in 14,590 MR images. The sensitivity and specificity of the derived deep neural network were 0.80 ± 0.03 and 0.88 ± 0.02, respectively. The Dice coefficient of the true positive lesions was 0.55 ± 0.02. The area under the curve of the receiver operating characteristic (AUC-ROC) curve of the deep neural network was 0.87 ± 0.02. The performance of the developed deep neural network was comparable to the interpretation of a radiologist with similar sensitivity and specificity. CONCLUSION: The developed deep neural network showed similar sensitivity and specificity to a radiologist with four years of experience. The results indicated that the network can provide a reliable and straightforward way of interpreting spinal MRI. The use of this deep neural network has the potential to expand the use of spinal MRI in managing axSpA.

Psychosocial Determinants of Knee Osteoarthritis Progression: Results from the Promoting Independence in Our Seniors with Arthritis Study.

BACKGROUND: Knee osteoarthritis (OA) is a common cause of physical disability among older adults. While established risk factors for knee OA include age and increased body weight, few studies have examined psychosocial risk factors or progression of knee OA. METHODS: The Promoting Independence in our Seniors with Arthritis study recruited participants aged 65 years and over from orthopedic outpatients and community engagement events. Participants were invited to annual visits during which knee OA symptoms were assessed with the Knee Injury and Osteoarthritis Outcome Score (KOOS), social network using the 6-item Lubben Social Network Scale and anxiety and depression using the Hospital Anxiety and Depression scale. Knee OA worsening was defined by a 5% reduction in mean KOOS scores at the last visit compared to the first visit. RESULTS: Data were available from 148 participants, mean age 66.2±6.5 years and 74.1% female, of whom 28 (18.9%) experienced OA worsening over a median follow-up period of 29 months. Univariate analyses revealed that age, sex, height, grip strength, and social network were associated with OA worsening. Social network remained statistically significantly associated with OA worsening after adjustment for age and sex difference (odds ratio=0.924; 95% confidence interval, 0.857-0.997). The relationship between social network and OA worsening were attenuated by both depression and handgrip strength at baseline. CONCLUSION: Psychological status and muscle strength may be modifiable risk factors for social network which may in turn prevent knee OA worsening and should be targeted in future intervention studies.

Risk of autoimmune diseases following COVID-19 and the potential protective effect from vaccination: a population-based cohort study.

Background: Case reports suggest that SARS-CoV-2 infection could lead to immune dysregulation and trigger autoimmunity while COVID-19 vaccination is effective against severe COVID-19 outcomes. We aim to examine the association between COVID-19 and development of autoimmune diseases (ADs), and the potential protective effect of COVID-19 vaccination on such an association. Methods: A retrospective cohort study was conducted in Hong Kong between 1 April 2020 and 15 November 2022. COVID-19 was confirmed by positive polymerase chain reaction or rapid antigen test. Cox proportional hazard regression with inverse probability of treatment weighting was applied to estimate the risk of incident ADs following COVID-19. COVID-19 vaccinated population was compared against COVID-19 unvaccinated population to examine the protective effect of COVID-19 vaccination on new ADs. Findings: The study included 1,028,721 COVID-19 and 3,168,467 non-COVID individuals. Compared with non-COVID controls, patients with COVID-19 presented an increased risk of developing pernicious anaemia [adjusted Hazard Ratio (aHR): 1.72; 95% Confidence Interval (CI): 1.12-2.64]; spondyloarthritis [aHR: 1.32 (95% CI: 1.03-1.69)]; rheumatoid arthritis [aHR: 1.29 (95% CI: 1.09-1.54)]; other autoimmune arthritis [aHR: 1.43 (95% CI: 1.33-1.54)]; psoriasis [aHR: 1.42 (95% CI: 1.13-1.78)]; pemphigoid [aHR: 2.39 (95% CI: 1.83-3.11)]; Graves' disease [aHR: 1.30 (95% CI: 1.10-1.54)]; anti-phospholipid antibody syndrome [aHR: 2.12 (95% CI: 1.47-3.05)]; immune mediated thrombocytopenia [aHR: 2.1 (95% CI: 1.82-2.43)]; multiple sclerosis [aHR: 2.66 (95% CI: 1.17-6.05)]; vasculitis [aHR: 1.46 (95% CI: 1.04-2.04)]. Among COVID-19 patients, completion of two doses of COVID-19 vaccine shows a decreased risk of pemphigoid, Graves' disease, anti-phospholipid antibody syndrome, immune-mediated thrombocytopenia, systemic lupus erythematosus and other autoimmune arthritis. Interpretation: Our findings suggested that COVID-19 is associated with an increased risk of developing various ADs and the risk could be attenuated by COVID-19 vaccination. Future studies investigating pathology and mechanisms would be valuable to interpreting our findings. Funding: Supported by RGC Collaborative Research Fund (C7154-20GF).

Physical and psychosocial characteristics differ between individuals with knee pain and different knee osteoarthritis diagnostic criteria.

PURPOSE: Knee pain and osteoarthritis (OA) are common and often lead to disability among older adults. Existing published evidence, however, utilizes differing criteria to define studies' knee OA populations. We, therefore, aimed to determine whether differences exist in the characteristics of individuals with the presence of knee pain and different diagnostic criteria for knee OA. METHODS: The Promoting Independence in Seniors with Arthritis (PISA) study is a longitudinal observational study of individuals with and without knee pain and knee OA recruited from the orthopaedics clinic of the Universiti Malaya Medical Centre and the local hospital catchment. Patients were diagnosed with OA based on the American College of Rheumatology (ACR) criteria, the presence of knee pain, and a history of physician-diagnosed knee OA. Psychosocial parameters were measured using validated measures for social participation, independence, and ability to perform activities of daily living, and life satisfaction. RESULTS: Of the 230 included participants, mean age was 66.9 years (standard deviation: 7.2) and 166 (72.2%) were women. Kappa agreement between ACR criteria and knee pain was 0.525 and for ACR and physician-diagnosed OA it was 0.325. Binomial logistic regression analysis showed that weight, anxiety, and handgrip strength (HGS) were predictive of ACR OA. Knee pain was only predicted by HGS but not weight and anxiety. Physician-diagnosed OA was predicted by weight and HGS but not anxiety. HGS was predictive of ACR OA, knee pain, and physician-diagnosed OA. CONCLUSION: Our study showed that the characteristics of patients with OA are different, physically and psychosocially, depending on the criteria used. Poor agreement was observed between radiological diagnosis and the other diagnostic criteria. Our findings have important implications for the interpretation and comparison of published studies using different OA criteria.

Risk and Factors associated with disease manifestations in systemic lupus erythematosus - lupus nephritis (RIFLE-LN): a ten-year risk prediction strategy derived from a cohort of 1652 patients.

Objectives: Lupus nephritis (LN) remains one of the most severe manifestations in patients with systemic lupus erythematosus (SLE). Onset and overall LN risk among SLE patients remains considerably difficult to predict. Utilizing a territory-wide longitudinal cohort of over 10 years serial follow-up data, we developed and validated a risk stratification strategy to predict LN risk among Chinese SLE patients - Risk and Factors associated with disease manifestations in systemic Lupus Erythematosus - Lupus Nephritis (RIFLE-LN). Methods: Demographic and longitudinal data including autoantibody profiles, clinical manifestations, major organ involvement, LN biopsy results and outcomes were documented. Association analysis was performed to identify factors associated with LN. Regression modelling was used to develop a prediction model for 10-year risk of LN and thereafter validated. Results: A total of 1652 patients were recruited: 1382 patients were assigned for training and validation of the RIFLE-LN model; while 270 were assigned for testing. The median follow-up duration was 21 years. In the training and validation cohort, 845 (61%) of SLE patients developed LN. Cox regression and log rank test showed significant positive association between male sex, age of SLE onset and anti-dsDNA positivity. These factors were thereafter used to develop RIFLE-LN. The algorithm was tested in 270 independent patients and showed good performance (AUC = 0·70). Conclusion: By using male sex, anti-dsDNA positivity, age of SLE onset and SLE duration; RIFLE-LN can predict LN among Chinese SLE patients with good performance. We advocate its potential utility in guiding clinical management and disease monitoring. Further validation studies in independent cohorts are required.

The Implementation of a Rib Fracture Pathway at a Small District General Hospital to Improve Patient Care.

Background and objective Rib fractures are common presentations to the emergency department following blunt thoracic trauma. Despite this injury causing significant morbidity and mortality, no national guidelines exist to guide the acute management of this condition. In light of this, this quality improvement project was conducted at a district general hospital (DGH) with the aim of assessing the impact of using a simple rib fracture management pathway. Methods A retrospective review of paper notes and electronic databases of patients with a recorded diagnosis of "rib fractures" were reviewed. Following this, a management pathway was designed and then implemented, which incorporated BMJ Best Practices and local hospital needs. The study then assessed the impact of the pathway. Results Prior to implementing the pathway, a total of 47 individual patients were included in the statistical analysis. Of the patients analysed, 44% were older than 65 years. Of note, 89% received regular paracetamol for analgesia, 41% received regular nonsteroidal anti-inflammatory drugs (NSAIDs), and 69% received regular opioids. Advanced analgesics such as patient-controlled analgesia (PCA) and nerve blocks were poorly used; for instance, a PCA was used in only 13% of cases. Only 6% of patients received daily pain team reviews and only 44% of patients were seen by physiotherapists within the first 24 hours. Additionally, 93% of patients who were admitted under general surgery had a STUMBL (STUdy of the Management of BLunt chest wall trauma) prognostic score >10. Post-pathway implementation, a total of 22 individual patients were included in the statistical analysis. Of them, 52% were older than 65 years. The use of simple analgesia was unchanged. However advanced analgesia was better escalated, and PCAs were used 43% of the time. The involvement of other healthcare professionals improved; 59% were reviewed by the pain team in the first 24 hours, 45% received daily pain team reviews, and 54% received advanced analgesia. Conclusion Based on our findings, implementing a simple rib fracture pathway is effective at improving the management of rib fracture patients admitted to our DGH.

Cardiovascular risk in rheumatoid arthritis patients treated with targeted synthetic and biological disease-modifying antirheumatic drugs: A multi-centre cohort study.

BACKGROUND: This study aimed to compare the cardiovascular safety of interleukin-6 inhibitors (IL-6i) and Janus Kinase inhibitors (JAKi) to tumour necrosis factor inhibitors (TNFi). METHODS: We conducted a retrospective cohort study using population-based electronic databases from Hong Kong, Taiwan and Korea. We identified newly diagnosed patients with rheumatoid arthritis (RA) who received b/tsDMARDs first time. We followed patients from b/tsDMARD initiation to the earliest outcome (acute coronary heart disease, stroke, heart failure, venous thromboembolism and systemic embolism) or censoring events (death, transformation of b/tsDMARDs on different targets, discontinuation and study end). Using TNFi as reference, we applied generalized linear regression for the incidence rate ratio estimation adjusted by age, sex, disease duration and comorbidities. Random effects meta-analysis was used for pooled analysis. RESULTS: We identified 8689 participants for this study. Median (interquartile range) follow-up years were 1.45 (2.77) in Hong Kong, 1.72 (2.39) in Taiwan and 1.45 (2.46) in Korea. Compared to TNFi, the adjusted incidence rate ratios (aIRRs) (95% confidence interval [CI]) of IL-6i in Hong Kong, Taiwan and Korea are 0.99 (0.25, 3.95), 1.06 (0.57, 1.98) and 1.05 (0.59, 1.86) and corresponding aIRR of JAKi are 1.50 (0.42, 5.41), 0.60 (0.26, 1.41), and 0.81 (0.38, 1.74), respectively. Pooled aIRRs showed no significant risk of cardiovascular events (CVEs) associated with IL-6i (1.05 [0.70, 1.57]) nor JAKi (0.80 [0.48, 1.35]) compared to TNFi. CONCLUSION: There was no difference in the risk of CVE among RA patients initiated with IL-6i, or JAKi compared to TNFi. The finding is consistent in Hong Kong, Taiwan and Korea.

MRI lesions in SpA: a comparison with noninflammatory back pain using propensity score adjustment method.

Background: Magnetic resonance imaging (MRI) is important in the management of axial spondyloarthritis (SpA). However, many MRI lesions are not exclusive to axial SpA. Further characterization of these lesions may lead to better clinical decisions. Objective: The objective of this study was to compare the frequency of individual spinal MRI lesions between axial SpA and noninflammatory back pain. The factors associated with individual lesions in participants with axial SpA were also determined. Design: This was a cross-sectional observational study. Methods: MRI lesions in 447 participants with axial SpA and 122 participants with noninflammatory back pain were compared using the propensity score adjustment method. Individual lesions included discovertebral lesions (DVL), Modic type 1 lesions, DVL without Modic type 1 lesions, facet joint lesions, costovertebral joint lesions, corner inflammatory lesions (CIL), and fatty corner lesions (FCL). The factors associated with the lesions were determined using regression analyses. Results: Among participants with axial SpA, 81.9% were HLA-B27-positive, 55.0% had radiographic axial SpA, and 60.5% had radiographic features of spinal damage (mSASSS >2). Almost half (48.6% in axial SpA versus 31.1% in noninflammatory back pain) had inflammatory lesions on spinal MRI. In propensity score matching with noninflammatory back pain, axial SpA had an increased occurrence of DVL without Modic type 1 lesion (OR = 3.43, p = 0.01), costovertebral lesion (OR = 11.89, p = 0.02), number of CIL (B = 1.19, p < 0.001), and number of FCL (B = 3.33, p < 0.001). Similar associations were found in the regression models in the radiographic axial SpA subgroup: DVL without Modic type 1 lesion (OR = 2.46, p = 0.001), costovertebral lesion (OR = 3.86, p < 0.001), number of CIL (B = 1.13, p < 0.001), and FCL (B = 2.29, p < 0.01). Conclusion: MRI lesions including DVL without Modic type 1, costovertebral joint lesions, CIL, and FCL were more specific in axial SpA.

NET Rounding: a novel approach to efficient and effective rounds for the modern clinical learning environment.

BACKGROUND: Rounds are a foundational practice in patient care and education in the inpatient healthcare environment, but increased demands on inpatient teams have led to dissatisfaction with inefficient, ineffective rounds. In this study, we describe the design, implementation, and evaluation of a novel rounding framework ("NET Rounding") that provides behaviorally-based strategies to inpatient teams to achieve efficient rounds while preserving patient safety and education. METHODS: NET Rounding consists of nine recommendations divided into three categories: Novel rounding strategies, shared Expectations, and Time management. This framework was introduced as a bundled intervention at a single-site, quaternary-care, academic hospital from March-May 2021. Eighty-three residents and 64 attendings rotated on the inpatient teaching service during the intervention period. Participants were surveyed before, during, and after their rotation about rounding's contribution to educational value, patient safety, resident duty hour violations and rotation experience. Additionally, rounding duration was recorded daily by team attendings. RESULTS: Thirty-two residents (38.5%) and 45 attendings (70%) completed post-intervention surveys. Rounding duration was recorded on 529/626 rounding days (80.6%) and resulted in achieving efficient rounds on 412/529 days (77.9%). Residents reported improvement in perceived patient safety (54 to 84%, p = 0.0131) and educational value of rounds (38 to 69%, p = 0.0213) due to NET Rounding; no change was observed amongst attendings in these areas (79 to 84% and 70 to 80%, p = 0.7083 and 0.4237, respectively). Overall, 29/32 residents (91%) and 33/45 attendings (73%) reported a positive impact on rotation experience. CONCLUSIONS: NET Rounding enabled inpatient teaching teams to complete rounds more efficiently while preserving patient safety and education.

Clinical, radiological, and magnetic resonance imaging characteristics of axial spondyloarthritis with late onset.

We aimed to investigate the clinical, diagnostic, and imaging features of patients with late onset axial spondyloarthritis (SpA) with initial symptom manifestation aged over 45 years. Participants with axial SpA were consecutively recruited. Clinical, demographic, blood, and imaging parameters were compared between the groups with early (≤45 years) and late onset (>45 years) at a cross-sectional level. Logistic regressions were used to determine the independent associations with axial SpA with late onset. A total of 455 participants were recruited. Among them, 70 (15.4%) had late onset disease. Multivariate analyses showed that axial SpA with late onset was associated with higher C-reactive protein based ankylosing spondylitis disease activity index (ASDAS-CRP) (B = 0.10; P = .04), higher intensity of spinal inflammation as measured by maximum apparent diffusion coefficient (spinal ADC max) (B = 0.27; P = .03) and mean ADC (spinal ADC mean) (B = 0.30; P = .004), lower modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) (B = -0.12; P = .02), more tender joint count (B = 0.12; P = .02), and fewer inflammatory back pain (IBP) (OR = 0.26; P < .001). Axial SpA with late onset had higher clinical disease activity, higher intensity of spinal MRI inflammation, less radiographic damage, and more tender joint count. There was also less inflammatory back pain, which could make the diagnosis more difficult.

Risk of nonpulmonary infections requiring hospitalization in spondyloarthritis.

OBJECTIVES: To compare the risk of five nonpulmonary infections leading to hospitalization between spondyloarthritis (SpA) and nonspecific back pain (NSBP), and to identify the risk factors. METHODS: A total of 3018 patients with SpA and 2527 patients with NSBP were identified. Data from December 1995 to June 2019 was retrieved from a centralized electronic medical record system. The date of onset of five types of nonpulmonary infections including: urinary tract infection (UTI), skin infection, gastroenteritis (GE), septic arthritis, and pancreato-hepatobiliary tract infection were identified. Demographic data, comorbidities, and medications used were also retrieved. Comparative risk of each type of infection between SpA and NSBP was determined using propensity score adjustment method. Cox regression model was used to identified risk factors. RESULTS: Patients with SpA were younger in age, predominantly male, with fewer comorbid diabetes mellitus (DM), renal impairment, and depression. Compared with NSBP, patients with SpA had higher risk of UTI (hazard ratio [HR] 1.91; p < .001), skin infection (HR 1.79; p < .001), and septic arthritis (HR 4.57; p = .04). Risk of GE (HR 1.42; p = 1.00), and pancreato-hepatobiliary tract infection (HR 1.67; p = .06) were not increased. Infliximab was an independent risk factor for UTI (HR 2.21; p = .04). Duration of steroid therapy >6 months (HR 2.22; p < .001), smoker (HR 1.81; p < .001), and psoriasis (HR 2.47; p < .001) were risk factors for skin infection. CONCLUSION: SpA was associated with increased risk of UTI, skin infection, and septic arthritis. Infliximab, prolonged steroid therapy, smoking, and psoriasis were associated risk factors.

Deep learning algorithms for magnetic resonance imaging of inflammatory sacroiliitis in axial spondyloarthritis.

OBJECTIVE: The aim of this study was to develop a deep learning algorithm for detection of active inflammatory sacroiliitis in short tau inversion recovery (STIR) sequence MRI. METHODS: A total of 326 participants with axial SpA, and 63 participants with non-specific back pain (NSBP) were recruited. STIR MRI of the SI joints was performed and clinical data were collected. Region of interests (ROIs) were drawn outlining bone marrow oedema, a reliable marker of active inflammation, which formed the ground truth masks from which 'fake-colour' images were derived. Both the original and fake-colour images were randomly allocated into either the training and validation dataset or the testing dataset. Attention U-net was used for the development of deep learning algorithms. As a comparison, an independent radiologist and rheumatologist, blinded to the ground truth masks, were tasked with identifying bone marrow oedema in the MRI scans. RESULTS: Inflammatory sacroiliitis was identified in 1398 MR images from 228 participants. No inflammation was found in 3944 MRI scans from 161 participants. The mean sensitivity of the algorithms derived from the original dataset and fake-colour image dataset were 0.86 (0.02) and 0.90 (0.01), respectively. The mean specificity of the algorithms derived from the original and the fake-colour image datasets were 0.92 (0.02) and 0.93 (0.01), respectively. The mean testing dice coefficients were 0.48 (0.27) for the original dataset and 0.51 (0.25) for the fake-colour image dataset. The area under the curve of the receiver operating characteristic (AUC-ROC) curve of the algorithms using the original dataset and the fake-colour image dataset were 0.92 and 0.96, respectively. The sensitivity and specificity of the algorithms were comparable with the interpretation by a radiologist, but outperformed that of the rheumatologist. CONCLUSION: An MRI deep learning algorithm was developed for detection of inflammatory sacroiliitis in axial SpA.

Both ASDAS and ADC are associated with spinal mobility in active axial spondyloarthritis: A comparison between early and later disease.

OBJECTIVE: Using diffusion-weighted imaging (DWI)-derived apparent diffusion coefficient (ADC), we aimed to determine the relationship between intensity of spinal inflammation and mobility in patients with axial spondyloarthritis (SpA) in early and later stages of active disease. The Ankylosing Spondylitis Disease Activity Score (ASDAS) was also used for a more comprehensive evaluation. METHODS: Participants with axial SpA and back pain were recruited from 10 rheumatology centers. Clinical, biochemical and radiological parameters were collected. Short tau inversion recovery (STIR) sequence magnetic resonance imaging (MRI) and DWI of the spine and sacroiliac (SI) joints were performed. ADC maps were generated. Participants were examined for Bath Ankylosing Spondylitis Metrology Index (BASMI). Linear regression models were used to determine associations between BASMI and various clinical, radiological, and MRI parameters in participants with active inflammation on spinal ADC maps. RESULTS: One-hundred and twenty-seven participants were included in the analyses. Multivariate linear regression showed that mean ADC spine (ß = .16; P = .03), ASDAS-C-reactive protein (CRP) (ß = .29, P < .001), and ASDAS-erythrocyte sedimentation rate (ESR) (ß = .25, P < .01) were associated with BASMI. In participants with duration of back pain ≤3 years, mean spine ADC (ß = .37; P = .03), ASDAS-CRP (ß = .44; P = .01), and ASDAS-ESR (ß = .42; P = .01) were associated with BASMI after adjustment for confounding factors. In participants with duration of back pain >3 years, only ASDAS-CRP (ß = .25; P < .01) and ASDAS-ESR (ß = .20; P = .20) were associated with BASMI. CONCLUSION: Intensity of inflammation and clinical disease activity were independently associated with impairment of spinal mobility. The associations were stronger in early (≤3 years) than later disease.

Conventional and Biologic Disease-Modifying Antirheumatic Drugs Are Not Associated With Increase in or Progression of Cervical Neoplasia Among Patients With Spondyloarthritis.

OBJECTIVES: Using a centralized electronic database, we investigated the risk of cervical neoplasia (CN) and progression of cervical intraepithelial neoplasia (CIN) among patients with spondyloarthritis (SpA) receiving disease-modifying antirheumatic drugs (DMARDs). METHOD: A total of 951 patients with SpA were reviewed. Incidence and progression of CN and clinical data including age, ethnicity, smoking and drinking status, dates of first and last follow-up, history of psoriasis, inflammatory bowel disease, medications used, mean dose and duration of medications, and comorbidities were reviewed. Cox regression models were used to evaluate the individual risk of DMARDs with CN and the risk of CIN progression. RESULTS: During a mean follow-up duration of 9.2 ± 5.9 years, 34 patients had developed CN, which translates to an incidence for development of CN in patients with SpA of 3.9 per 1000 patient-years. Univariate Cox regression analyses showed no differences in clinical characteristics (psoriasis hazards ratio [HR] = 0.92, p = 0.82; inflammatory bowel disease HR = 0.05, p = 0.61; diabetes mellitus HR = 2.82, p = 0.21; chronic kidney disease HR = 0.39, p = 0.35) and medications exposure (sulfasalazine HR = 0.49, p = 0.30; methotrexate HR = 0.52, p = 0.11; leflunomide HR = 0.52, p = 0.37; adalimumab HR = 0.83, p = 0.80; certolizumab HR = 0.05, p = 0.74; etanercept HR = 0.40, p = 0.36; golimumab HR = 0.05, p = 0.32; infliximab HR = 0.05, p = 0.39; secukinumab HR = 1.00, p = 1.00; ustekinumab HR = 0.05, p = 0.78) between patients who had and had not develop CN during the study period. Progression of CIN was independently associated with higher grades of CIN lesion (HR = 6.20; p = 0.05). CONCLUSIONS: There was low risk of development and progression of CN in patients with SpA on conventional or biologic DMARD therapy.

Malignancies in spondyloarthritis with and without concomitant psoriasis, and the effect of disease modifying anti-rheumatic drugs.

OBJECTIVES: To determine the risk of 6 types of malignancies in spondyloarthritis (SpA) with and without psoriasis (PsO) and on disease-modifying anti-rheumatic drugs (DMARDs), compared to non-specific back pain (NSBP). METHODS: Medical records were retrieved. Patients with SpA with and without PsO were identified and compared to those with NSBP. Clinical data; follow-up duration; comorbidities; dates and types of cancer diagnosed; types and duration of DMARD therapy were collected. Propensity score adjustment was used to compare the risks of malignancies between SpA, SpA with and without PsO, and NSBP. Cox regression analysis was used to determine the risk of malignancy in DMARD therapy. RESULTS: A total of 3020 patients with SpA and 2527 patients with NSBP were studied. The mean follow-up duration in patients with SpA and NSBP was 9.6 years and 13.5 years respectively. Incidence and risk of malignancies were compatible between SpA and NSBP. The incidences of various carcinomas (per 1000 patient-years) in SpA were: 1.37 for colorectal carcinoma; 0.30 for carcinoma of pancreas; 0.30 for carcinoma of stomach; and 0.91 for lymphomas. Risk of colorectal carcinoma (HR 2.46; p=0.03) and lymphomas (HR 2.86; p=0.04) was increased in SpA with concomitant PsO. DMARD therapy was not associated with increased risks of malignancies after adjustment for confounding factors. CONCLUSIONS: Risk of malignancy was increased in SpA with PsO but not in other subtypes of SpA or DMARD therapy.

Epidemiology, mortality and effectiveness of prophylaxis for Pneumocystis jiroveci pneumonia among rheumatic patients: a territory-wide study.

BACKGROUND: Pneumocystis jiroveci pneumonia (PJP) is an opportunistic infection affecting immunocompromised individuals. However, evidence regarding the burden and effectiveness of prophylaxis among rheumatic patients remains limited. Delineating the epidemiology and efficacy of prophylaxis among rheumatic patients is urgently needed. METHODS: We performed a territory-wide cohort study of rheumatic patients in Hong Kong. All patients with a diagnosis of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), immune-mediated myositis (IMM), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), or spondyloarthritis (SpA) between 2015 and 2019 were included. Prevalence, frequency of prophylaxis and mortality of PJP were calculated. Number needed to treat (NNT) analysis was also performed. RESULTS: Out of 21,587 patients (54% RA, 25% SLE, 13% SpA, 5% IMM, 2% AAV and 1% SSc), 1141 (5.3%) patients were prescribed PJP prophylaxis. 48/21,587 (0.2%) developed PJP. No patients who developed PJP received prophylaxis prior to infection. The incidence of PJP was highest among SSc, AAV, and IMM patients. Among these diseases, the majority of PJP occurred while patients were on glucocorticoids at daily prednisolone-equivalent doses of 15 mg/day (P15) or above. PJP prophylaxis was effective with NNT for SSc, AAV and IIM being 36, 48 and 114 respectively. There were 19 PJP-related mortalities and the mortality rate was 39.6%. CONCLUSION: PJP is an uncommon but important infection among rheumatic patients, PJP prophylaxis is effective and should be considered in patients with SSc, AAV and IMM, especially those receiving glucocorticoid doses above P15.