Background: Interstitial lung disease (ILD) related to rheumatoid arthritis (RA) is among the leading causes of death and an essential prognostic factor. There is only limited evidence for the safety of anti-rheumatic drugs for patients with RA-ILD. The aim of this study is to investigate the safety and efficacy of Janus kinase inhibitors (JAKis) by comparing it with abatacept (ABT) in patients with RA-ILD.
Methods: This single centre, retrospective nested case-control study enrolled patients with RA-ILD treated with JAKi or ABT. To determine the safety of the two drugs for existing ILD, we compared their drug persistency, incidence rates of pulmonary complications, and change of chest computed tomography (CT) image. For their efficacy as RA treatment, disease activity scores and prednisolone (PSL)-sparing effect were compared. We performed propensity score matching to match the groups' patient characteristics.
Results: We studied 71 patients with RA-ILD (ABT, n = 45; JAKi, n = 26). At baseline, the JAKi group had longer disease duration, longer duration of past bDMARD or JAKi use and higher usual interstitial pneumonia rate. After propensity score matching, no significant differences in patient characteristics were found between the two groups. No significant difference in the drug persistency rate for the first 2 years (ABT, 61.9%; JAKi, 42.8%; P = 0.256) was observed between the two matched groups. The incidence rate of pulmonary complications did not differ significantly between the two groups (P = 0.683). The CT score did not change after the treatment for the ABT group (Ground-glass opacities (GGO): P = 0.87; fibrosis: P = 0.78), while the GGO score significantly improved for the JAKi group (P = 0.03), although the number was limited (ABT: n = 7; JAKi: n = 8). The fibrosis score of the JAKi group did not change significantly.(P = 0.82). Regarding the efficacy for RA, a significant decrease in disease activity scores after the 1-year treatment was observed in both groups, and PSL dose was successfully tapered, although no significant differences were observed between the two drugs.
Conclusions: JAKi is as safe and effective as ABT for patients with RA-ILD. JAKi can be a good treatment option for such patients.
Introduction: Ankylosing spondylitis(AS) is a chronic inflammatory rheumatic disease primarily affecting the spine and sacroiliac joints. While biologic disease-modifying antirheumatic drugs(bDMARDs) and targeted synthetic DMARDs(tsDMARDs) are popular treatments for AS, there is limited research on their combined use. This study examined a cohort of AS patients who demonstrated inadequate response to bDMARDs and subsequently initiated combination therapy with tofacitinib in conjunction with bDMARDs, assessing both the efficacy and safety profile of this therapeutic approach.
Methods: In this study, we retrospectively collected the electronic medical records (EMR) of 15 adult patients with AS who were admitted to the Fourth Affiliated Hospital Zhejiang University School of Medicine between January 2018 and June 2022. All patients had received at least one bDMARD treatment for more than three months and still exhibited moderate to high disease activity. Tofacitinib 5 mg bid was added to their original biological treatment. Treatment was continued for a minimum of 12 weeks following the initiation of combination therapy. Changes in ASDAS-CRP and BASDAI scores at week 12 were collected and analyzed from baseline, while changes in C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) at weeks 4, 8, and 12 were also collected and analyzed.
Results: After 12 weeks of treatment, the overall ASDAS-CRP score decreased significantly from a baseline of 3.82 ± 1.47 (2.83 ~ 4.99) to 1.47 ± 0.48 (0.75 ~ 2.44), with remission achieved by 7 patients (46.7%) and low disease activity achieved by 5 patients (33.3%). The overall BASDAI score also showed significant improvement, decreasing from a baseline of 5.11 ± 1.42 (3.25 ~ 7 0.75) to 1.28 ± 0.70(0.20 ~ 2.55). Additionally, both ESR and CRP levels decreased significantly during the course of treatment without any reported adverse events leading to discontinuation.
Conclusion: To a certain extent, our findings provide some evidence supporting the efficacy and safety of the combination of bDMARD and JAK inhibitor tofacitinib in AS patients with inadequate response to bDMARD monotherapy. It effectively controls disease activity while maintaining a relatively low and manageable incidence of adverse events. Further prospective randomized controlled trials with large sample sizes are anticipated to provide evidence-based medical support.
Background: This study aimed to assess the association between social factors, demographic parameters, and disease activity among rheumatoid arthritis (RA) patients.
Methods: The University of Pittsburgh Rheumatoid Arthritis Comparative Effectiveness Research (RACER) registry was used for this study and included patients meeting 1987 ACR criteria for RA enrolled between 2010-2015. The registry collected clinical and laboratory data at each visit, permitting the calculation of disease activity measures that included Disease Activity 28-C Reactive Protein (DAS28-CRP). The current study was conducted as a cross-sectional study in which baseline data were used to construct multiple logistic regression models assessing the relationship between disease activity measures (DAS28-CRP), functional capacity (health assessment questionnaire (HAQ)), selected demographic and social factors (occupation, education, income, marital status, race, gender, age, and BMI), and clinical/laboratory variables.
Results: The analyses included 729 patients with baseline DAS28-CRP and social/demographic data. The mean age at enrollment was 59.5 (Standard Deviation (SD) = 12.7) years, 78% were female, and the median RA disease duration was 9.8 (Interquartile Range (IQR): 3.7, 19.1) years. We dichotomized the DAS28-CRP score and defined scores above or below 3.1 as high versus low RA disease activity. Most patients with high RA disease activity (N = 326, 45%) had less than a college degree (70%), were not working/retired/disabled (71%), and had an annual income under $50 K (55%). We found that higher body mass index (BMI) (Odds Ratio (OR) = 1.04, 95% CI: 1.01-1.08), longer disease duration (> 2 and < 10 years versus ≤ 2 years of disease) (OR = 0.45, 95% CI: 0.25-0.78), and being retired (OR = 1.74, 95% CI: 1.02-2.98) were associated with RA disease activity.
Conclusion: Increased RA activity may be associated with various social factors, potentially leading to more severe and debilitating disease outcomes. These findings provide evidence to support efforts to monitor disparities and achieve health equity in RA.
Background: Janus kinase inhibitors (JAKi) are new targeted synthetic disease-modifying antirheumatic drugs (DMARDs) licenced in the UK to treat rheumatoid and psoriatic arthritides. Unlike currently often prescribed biological DMARDs, they target a different part of the inflammatory pathway and are taken orally. The aim of this study was to explore what UK-based rheumatology clinicians and inflammatory arthritis (IA) patients think about the awareness, prescription and use of JAKi; how they compare with biologics; and how the COVID-19 pandemic has affected how JAKi are viewed and prescribed.
Methods: Rheumatology clinicians and IA patients completed online surveys and participated in interviews/focus groups between September 2021 and January 2022. Survey data were analysed descriptively, and interview/focus group data underwent an inductive thematic analysis.
Results: 66.6% of patients had at least some awareness of JAKi, 73.0% from their rheumatology team. Problems getting earlier access to these drugs were raised by some patients, with many being prescribed JAKi after multiple other therapies had failed. 91.5% of clinicians prescribed JAKi in keeping with their local guidelines, with 72.3% prescribing them frequently as a monotherapy. Some clinicians had lingering safety concerns over JAKi use. Despite experiencing side effects and knowing of possible long-term risks, patients felt overall the benefits of JAKi outweighed the risks. 39.3% of patients were 'very satisfied' on JAKi, compared with 25.0% on biologics. Patients on JAKi appreciated their short half-life when it comes to infections, and their convenience as an oral therapy. When JAKi were discontinued in patients, it was predominantly due to inefficacy and non-cardiovascular adverse events. The COVID-19 pandemic resulted in increased prescription of JAKi as an alternative to injections and infusions, primarily to avoid potentially exposing patients to the coronavirus. Some patients believed their JAKi may confer some protection against developing severe COVID-19.
Conclusion: JAKi are an effective treatment option for IA and are liked by patients. The COVID-19 pandemic appears to have impacted their prescription favourably. However, clinicians have safety concerns over JAKi use. Any decision to go on a JAKi should be informed and take into account individual patient risk factors, circumstances and preferences.
Background: Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disease characterized by clinical and pathological diversity. Mitochondrial dysfunction has been identified as a critical pathogenetic factor in SLE. However, the specific molecular aspects and regulatory roles of this dysfunction in SLE are not fully understood. Our study aims to explore the molecular characteristics of mitochondria-related genes (MRGs) in SLE, with a focus on identifying reliable biomarkers for classification and therapeutic purposes.
Methods: We sourced six SLE-related microarray datasets (GSE61635, GSE50772, GSE30153, GSE99967, GSE81622, and GSE49454) from the Gene Expression Omnibus (GEO) database. Three of these datasets (GSE61635, GSE50772, GSE30153) were integrated into a training set for differential analysis. The intersection of differentially expressed genes with MRGs yielded a set of differentially expressed MRGs (DE-MRGs). We employed machine learning algorithms-random forest (RF), support vector machine (SVM), and least absolute shrinkage and selection operator (LASSO) logistic regression-to select key hub genes. These genes' classifying potential was validated in the training set and three other validation sets (GSE99967, GSE81622, and GSE49454). Further analyses included differential expression, co-expression, protein-protein interaction (PPI), gene set enrichment analysis (GSEA), and immune infiltration, centered on these hub genes. We also constructed TF-mRNA, miRNA-mRNA, and drug-target networks based on these hub genes using the ChEA3, miRcode, and PubChem databases.
Results: Our investigation identified 761 differentially expressed genes (DEGs), mainly related to viral infection, inflammatory, and immune-related signaling pathways. The interaction between these DEGs and MRGs led to the identification of 27 distinct DE-MRGs. Key among these were FAM210B, MSRB2, LYRM7, IFI27, and SCO2, designated as hub genes through machine learning analysis. Their significant role in SLE classification was confirmed in both the training and validation sets. Additional analyses included differential expression, co-expression, PPI, GSEA, immune infiltration, and the construction of TF-mRNA, miRNA-mRNA, and drug-target networks.
Conclusions: This research represents a novel exploration into the MRGs of SLE, identifying FAM210B, MSRB2, LYRM7, IFI27, and SCO2 as significant candidates for classifying and therapeutic targeting.
Background: To investigate whether baseline serum cartilage oligomeric matrix protein (COMP), patient characteristics, traditional cardiovascular disease (CVD) risk factors and disease activity over time predict CVD, in early rheumatoid arthritis (RA).
Methods: This study included patients with early RA (< 12 months disease duration) (n = 233) recruited 1995-2005. Potential predictors of CVD and coronary artery disease (CAD) were assessed using Cox regression.
Results: A first ever diagnosis of CVD occurred in 70 patients, and CAD in 52. Age, sex, hypertension and diabetes predicted CVD and CAD. COMP was associated with increased risk of CVD and CAD [crude hazard ratios (HRs) per SD 1.45; 95% CI 1.17-1.80 and 1.51; 95% CI 1.18-1.92, respectively]. When adjusted for age, sex, hypertension, diabetes and ESR, results where similar but did not reach significance [HRs 1.32, 95% CI 0.99-1.74 and 1.35, 95% CI 0.99-1.86]. Baseline disease activity did not independently predict CVD. High DAS28 (> 5.1) at two years was associated with increased risk of subsequent CVD [adjusted HR 2.58; 95% CI 1.10-6.04] and CAD. ESR and CRP at two years as well as cumulative disease activity over 2 years independently predicted CVD and CAD.
Conclusion: COMP may be a novel predictor of CVD and CAD in RA. Active disease two years after RA diagnosis, as well as cumulative disease activity, was associated with increased risk of CVD and CAD, independent of traditional CVD risk factors. Awareness of the particularly increased CVD risk among difficult to treat patients is important in order to further reduce CVD in RA.
Background: Behcet disease (BD) as a variable vessel vasculitis is mainly characterized by ocular involvement, genital and oral aphthosis, and erythema nodosum. However, major organ involvements including gastrointestinal involvement, nervous system, and vascular involvement are among the severe complications. Osteonecrosis is a rare complication of patients with BD. We aim to report the largest series of BD patients suffering from osteonecrosis.
Methods: We have retrospectively reviewed all patients in Iran Behcet's Disease Registry and reported those with osteonecrosis. Patients' medication and clinical features, symptoms, and details of osteonecrosis will also be presented. Furthermore, previously reported cases will also be reviewed.
Results: Seven thousand eight hundred thirty-one patients were diagnosed with BD and registered. 18 patients developed ON with an incidence of 0.22%. The most common involvement during the disease progression was oral aphthosis which appeared in 100% of patients followed by ocular involvement in 85.7% and skin involvement in 71.4%. Vascular, ocular, and nervous system involvements are significantly higher in BD patients with osteonecrosis than the other BD patients. For the management of acute episode of uveitis, deep vein thrombosis, severe gastrointestinal involvement, arterial involvement, nervous system Involvement, and joint involvement high dose of glucocorticoids is indicated.
Conclusions: ON tends to appear as a multifocal involvement in BD patients, hence, after diagnosis of ON in one joint other possible sites of ON should be investigated.
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