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ID PMID Title PublicationDate abstract
35040280 Provider Specialty and the Use of Disease-Modifying Antirheumatic Drugs for Rheumatoid Art 2022 Apr OBJECTIVE: We compared disease-modifying antirheumatic drug (DMARD) use for older adults with rheumatoid arthritis (RA)-related ambulatory visits from rheumatologists and primary care providers (PCPs). METHODS: In this study of national sample office visits, we characterized ambulatory visits by older adults 65 years of age or older seen by rheumatologists or PCPs for diagnosis of RA using the 2005-2016 National Ambulatory Medical Care Survey. We analyzed patterns and trends of DMARD use using descriptive statistics and multivariable analyses by provider specialty. RESULTS: We identified 518 observations representing 7,873,246 ambulatory RA visits by older adults over 12 years; 74% were with rheumatologists. Any DMARD use was recorded at 56% of rheumatologist and 30% of PCP visits. Among visits with any DMARD use, 20% of rheumatologist visits had two or more DMARDs compared with 6% of PCP visits. Over the 12-year study period, there was no statistical difference in trend of any or conventional synthetic DMARD use at visits by provider specialty, adjusted for patient characteristics, non-DMARD polypharmacy and multimorbidity. However, biologic DMARD use was more likely to incrementally increase with rheumatologist compared with PCP visits (P = 0.003). CONCLUSION: DMARD use for older adults with RA remains low from both rheumatologists and PCPs, including biologic DMARDs, even though American College of Rheumatology guidelines recommend earlier and more aggressive treatment of RA. With predicted shortages in the rheumatology workforce and maldistribution of rheumatology providers, PCPs may play an increasingly important role in caring for older adults with RA. Further research is needed to understand to optimize appropriate use of DMARDs in older patients with RA.
34782447 Characteristics, Comorbidities, and Outcomes of SARS-CoV-2 Infection in Patients With Auto 2022 Mar OBJECTIVE: To describe characteristics and coronavirus disease 2019 (COVID-19) clinical outcomes of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ulcerative colitis (UC) receiving systemic therapies vs the general population. METHODS: This descriptive retrospective cohort study used data from the United States Optum deidentified COVID-19 electronic health record dataset (2007-2020). Adults with COVID-19 were stratified into 3 disease cohorts (patients with RA, PsA, or UC who had received systemic therapy) and a comparator cohort not meeting these criteria. Incidence proportions of hospitalization and clinical manifestations of interest were calculated. Using logistic regression analyses, risk of endpoints was estimated, adjusting for demographics and demographics plus comorbidities. RESULTS: This analysis (February 1 to December 9, 2020) included 315,101 patients with COVID-19. Adjusting for demographics, COVID-19 patients with RA (n = 2306) had an increased risk of hospitalization (OR 1.54, 95% CI 1.39-1.70) and in-hospital death (OR 1.61, 95% CI 1.30-2.00) compared with the comparator cohort (n = 311,563). The increased risk was also observed when adjusted for demographics plus comorbidities (hospitalization OR 1.25, 95% CI 1.13-1.39 and in-hospital death OR 1.35, 95% CI 1.09-1.68]). The risk of hospitalization was lower in COVID-19 patients with RA receiving tumor necrosis factor inhibitors (TNFi) vs non-TNFi biologics (OR 0.32, 95% CI 0.20-0.53) and the comparator cohort (OR 0.77, 95% CI 0.51-1.17). The risk of hospitalization due to COVID-19 was similar between patients receiving tofacitinib and the comparator cohort. CONCLUSION: Compared with the comparator cohort, patients with RA were at a higher risk of more severe or critical COVID-19 and, except for non-TNFi biologics, systemic therapies did not further increase the risk. (ENCePP; registration no. EU PAS 35384).
34666946 India ink artifact on Dixon out-of-phase images can be used as a landmark to measure joint 2022 Feb PURPOSE: The purpose of this study was to test the feasibility of joint space width (JSW) measurement on Dixon MR images with the "India ink" artifact between cartilage and bone marrow as a landmark for the subchondral plate and to correlate it with radiographic JSW. MATERIALS AND METHODS: Both hands of six volunteers (three women, three men; mean age, 36.7 ± 10.4 [SD] years) and 24 patients with early rheumatoid arthritis (16 women, 8 men; mean age, 45.7 ± 14.5 [SD] years) were imaged with MRI Dixon sequences and radiographs. Two radiologists (R1, R2) separately measured JSW in 11 joints per hand on all Dixon images in volunteers, on contrast-enhanced T1-weighted out-of-phase images in patients and on radiographs in both groups. Inter-technique, intra-observer and inter-observer agreements were assessed using intraclass correlation coefficient (ICC) and Bland Altman analysis. RESULTS: In volunteers, agreement between JSW measurements on MRI and radiographs was the highest with T1-weighted Dixon out-of-phase images (mean ICC ranging from 0.69 to 0.76 for R1 and 0.65 to 0.74 for R2). In patients, median bias between JSW measurements at first and second readings was not statistically significantly different from 0 on T1-weighted Dixon out-of-phase images (mean bias of 0.00 and + 0.01 mm) and radiographs (mean bias of 0.00 and +0.01 mm). Median bias of the difference between measurements of R1 and R2 was statistically significantly different from 0 on T1-weighted Dixon out-of-phase images (mean bias of -0.11 and -0.09 mm; P < 0.039) and radiographs (mean bias of -0.24 and -0.20 mm; P < 0.035). CONCLUSION: Measurement of hand JSW on T1-weighted Dixon out-of-phase images using India ink artifact as a landmark for the subchondral plate is repeatable and reproducible.
35218463 Sarcococca saligna extract attenuates formaldehyde-induced arthritis in Wistar rats via mo 2022 Apr Sarcococca saligna plant is commonly used as traditional therapy for arthritis especially in Asian countries. The current study is designed to explore the anti-arthritic potential of S. saligna aqueous methanolic extract (SSME). Preliminary proximate study and HPLC analysis were performed to investigate the phytochemical characterization and quality control. The safety of the SSME was evaluated by performing an acute oral toxicity study (OECD guidelines 425). The anti-arthritic potential of SSME was explored by in vivo formaldehyde-induced arthritis model. The antiarthritic effect of the SSME was determined through paw diameter, arthritic index, body weight, biochemical and haematological parameters. Radiographic and histopathological studies were also carried out to evaluate the results. qRT-PCR was performed to determine the upregulation and downregulation of anti- and pro-inflammatory cytokines in rats while ELISA was done to determine the concentration of HSP-70, IL-6 and TNF-α in the serum. Results of acute oral toxicity showed no abnormality and mortality. There was no noticeable change in haematological and biochemical parameters. Histopathological examination exhibited the normal structure of vital organs. So, SSME might be safe at a 2000 mg/kg dose, proposing that LD(50) was higher than 2000 mg/kg body weight. Gallic acid, catechin, hydroxyl benzoic acid, sinapic acid, caffeic acid, ferulic acid and p-cumaric acid were identified by HPLC. The outcomes of in vivo formaldehyde-induced arthritic model showed that SSME significantly reduced paw inflammation and arthritic index and improved haematological and biochemical parameters. Moreover, the SSME influentially down-regulated the gene expression of IL-1β, IL-6, COX-2, PGE2, TNF-α and NF-κB, and up-regulated the expression of IL-4, and IL-10. The results of the undertaken study suggest that S. saligna have strong anti-arthritic activity supporting its conventional application as the remedy of rheumatoid arthritis.
35241924 Low-Dose Interleukin-2 Altered Gut Microbiota and Ameliorated Collagen-Induced Arthritis. 2022 PURPOSE: Low-dose interleukin-2 (ld-IL-2) has been shown to regulate the balance between effector T and regulatory T (Treg) cells and has been used in several clinical trials to treat autoimmune diseases including rheumatoid arthritis (RA). In this study, we investigated the effects of ld-IL-2 on collagen-induced arthritis (CIA) in mice. METHODS: Arthritis severity in CIA mice was measured using the arthritis index (AI), radiographs, and hematoxylin and eosin staining. Cytokines were detected using enzyme-linked immunosorbent assay. Gut microbiota alterations and short-chain fatty acid production were analyzed through 16S rRNA sequencing and gas chromatography. RESULTS: The AI scores of CIA mice treated with ld-IL-2 were significantly lower compared to the model group, which significantly reduced the severity of arthritis. Ld-IL-2 also altered the gut microbiota in CIA mice. The diversity, composition, and dominant species of gut microbiota were altered by ld-IL-2 treatment. Ld-IL-2 also increased short-chain fatty acid levels. There was a strong correlation between ld-IL-2 treatment and improved gut microbiota. CONCLUSION: Ld-IL-2 significantly ameliorated joint inflammation and bone damage and improved gut microbial dysbiosis in CIA, indicating that it may be a promising therapy for RA patients.
35014221 Rheumatoid Arthritis Synovial Inflammation Quantification Using Computer Vision. 2022 Apr OBJECTIVE: We quantified inflammatory burden in rheumatoid arthritis (RA) synovial tissue by using computer vision to automate the process of counting individual nuclei in hematoxylin and eosin images. METHODS: We adapted and applied computer vision algorithms to quantify nuclei density (count of nuclei per unit area of tissue) on synovial tissue from arthroplasty samples. A pathologist validated algorithm results by labeling nuclei in synovial images that were mislabeled or missed by the algorithm. Nuclei density was compared with other measures of RA inflammation such as semiquantitative histology scores, gene-expression data, and clinical measures of disease activity. RESULTS: The algorithm detected a median of 112,657 (range 8,160-821,717) nuclei per synovial sample. Based on pathologist-validated results, the sensitivity and specificity of the algorithm was 97% and 100%, respectively. The mean nuclei density calculated by the algorithm was significantly higher (P < 0.05) in synovium with increased histology scores for lymphocytic inflammation, plasma cells, and lining hyperplasia. Analysis of RNA sequencing identified 915 significantly differentially expressed genes in correlation with nuclei density (false discovery rate is less than 0.05). Mean nuclei density was significantly higher (P < 0.05) in patients with elevated levels of C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, and cyclized citrullinated protein antibody. CONCLUSION: Nuclei density is a robust measurement of inflammatory burden in RA and correlates with multiple orthogonal measurements of inflammation.
35545952 The changing incidence of rheumatoid arthritis over time in north-west Greece: data from a 2022 May 12 OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown aetiology that affects approximately 1% of the population. The disease presents a temporal variability in different geographic areas. We investigated RA incidence over a 40-year-period in a defined area of north-west Greece, with a total population of about 400 000 inhabitants. METHOD: This incidence study was based on retrospective review of clinical records among adults with RA newly diagnosed from 1980 to 2019 at the referral university hospital of Ioannina. An incident case was defined as any patient diagnosed with RA based on the 1987 American College of Rheumatology criteria, over 16-years-old, and resident in the study area for at least 1 year before diagnosis. RESULTS: Out of 1411 cases diagnosed, women constituted a 2.65-fold higher number than men, with a lower mean age at diagnosis. The overall age-adjusted annual incidence rate (95% confidence interval) was 9.5 (8.5-10.5) for the total observation period, 11.7 (10.7-13.0) in 1980-1989, 10.4 (9.4-10.8) in 1990-1999, 9.8 (8.9-10.8) in 2000-2009, and 6.1 (5.3-6.9) in 2010-2019, presenting a statistically significant decline over time, along with a constant decrease in rheumatoid factor (RF)-positive incidence for both sexes. CONCLUSION: Our findings suggest a decrease in the incidence of RA over 40 years in a geographically defined Greek population. Also, the progressive decrease in the incidence of RF-positive disease may relate to less severe expression of RA in Greek patients. These trends could be explained by different clinical, serological, and genetic factors reported in Greece compared to northern European countries.
35207282 Antibodies to Porphyromonas gingivalis Are Increased in Patients with Severe Periodontitis 2022 Feb 15 There is accumulating data suggesting that periodontitis is associated with increased risk of systemic and autoimmune diseases, including cardiovascular disease, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), and there is an unmet need to identify these individuals early. With the periodontal bacteria Porphyromonas gingivalis (Pg) as one of the key drivers of periodontitis, we set out to investigate whether antibodies to Pg virulence factor arginine gingipain (Rgp) could serve as a biomarker for periodontitis patients at increased risk of autoimmunity and systemic disease. We measured serum anti-Rgp IgG in three study populations: PAROKRANK (779 individuals with myocardial infarction (MI); 719 controls), where 557 had periodontitis, and 312 were positive for autoantibodies associated with RA/SLE; the PerioGene North pilot (41 periodontitis; 39 controls); and an SLE case/control study (101 SLE; 100 controls). Anti-Rgp IgG levels were increased in severe periodontitis compared to controls (p < 0.0001), in individuals positive for anti-citrullinated protein antibodies (p = 0.04) and anti-dsDNA antibodies (p = 0.035), compared to autoantibody-negative individuals; and in MI patients versus matched controls (p = 0.035). Our data support longitudinal studies addressing the role of anti-Rgp antibodies as biomarkers for periodontitis patients at increased risk of developing autoimmunity linked to RA and SLE, and mechanisms underpinning these associations.
35136990 Selection of treatment regimens based on shared decision-making in patients with rheumatoi 2022 Feb 8 OBJECTIVE: To compare the outcome of various treatment de-escalation regimens in patients with RA who achieved sustained remission. METHODS: At period 1, 436 RA patients who were treated with MTX and bDMARDs and had maintained DAS28(ESR) at < 2.6 were divided into five groups based on shared patient/physician decision-making; continuation, dose-reduction and discontinuation of MTX or bDMARD. At end of year 1, patients who achieved DAS28(ESR)<3.2 were allowed to enrol in period 2 for treatment using the de-escalation regimens for another year. The primary and secondary endpoints were the proportion of patients with DAS28(ESR)<2.6 at year 1 and 2, respectively. RESULTS: Based on shared decision-making, 81.4% elected de-escalation of treatment and 48.4% selected de-escalation of MTX. At end of period 1, similar proportions of patients maintained DAS28(ESR)<2.6 (continuation, 85.2%; MTX-dose-reduction, 79.0%; MTX-discontinuation, 80.0%; bDMARD-dose-reduction, 73.9%), although the rate was significantly different between the continuation and bDMARD-discontinuation. At end of period 2, similar proportions of patients of the MTX groups maintained DAS28(ESR)<2.6 (continuation or de-escalation), but the rates were significantly lower in the bDMARD-discontinuation group. However, half of the latter group satisfactorily discontinued bDMARD. Adverse events were numerically lower in MTX and bDMARD-de-escalation groups during period 1 and 2, compared with the continuation group. CONCLUSIONS: After achieving sustained remission by combination treatment of MTX/bDMARDs, disease control was achieved comparably by continuation, dose-reduction or discontinuation of MTX and dose-reduction of bDMARD at end of year 1. Subsequent de-escalation of MTX had no impacts on disease control but decreased adverse events in year 2.
34880054 Whole gut virome analysis of 476 Japanese revealed a link between phage and autoimmune dis 2022 Feb OBJECTIVE: The relationship between autoimmune diseases and the gut microbiome has been intensively studied, and several autoimmunity-associated bacterial taxa have been identified. However, much less is known about the roles of the gut virome in autoimmune diseases. METHODS: Here, we performed a whole gut virome analysis based on the shotgun sequencing of 476 Japanese which included patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis and healthy control subjects. RESULTS: Our case-control comparison of the viral abundance revealed that crAss-like phages, which are one of the main components of a healthy gut virome, significantly decreased in the gut of the patients with autoimmune disease, specifically the patients with RA and SLE. In addition, Podoviridae significantly decreased in the gut of the patients with SLE. To understand how these viruses affected the bacteriome, we performed a quantitative virus-bacterium association analysis and clustered regularly interspaced short palindromic repeat-based virus-bacterium interaction analysis. We identified a symbiosis between Podoviridae and Faecalibacterium. In addition, multiple bacterial targets of crAss-like phages were identified (eg, Ruminococcus spp). CONCLUSION: Our data suggest that the gut virome can affect our body either directly or via bacteria. Our analyses have elucidated a previously missing part of the autoimmunity-associated gut microbiome and presented new candidates that contribute to the development of autoimmune diseases.
35084309 Adherence of Italian rheumatologists to the EULAR recommendations and outcomes in early rh 2022 Jan 12 OBJECTIVES: The aim of this study was to assess the real-life adherence of Italian rheumatologist to the 2013 EULAR recommendations and treatment outcome in rheumatoid arthritis (RA) patients who started a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD). METHODS: The MITRA study is an Italian multicentre observational cohort focused on treatment naïve RA patients with early diagnosis recruited in an 18-month period starting from 2015. The data related to treatment with csDMARDs during the following 12 months follow-up were presented in this paper. RESULTS: Two-hundred and fifty-nine RA patients from MITRA cohort who had a follow-up visit and started a csDMARD were included in the prospective analysis. Methotrexate was started as first conventional DMARD in 224 (86.4%) patients. During the first year after starting conventional DMARDs, 175 (67.6%) RA patients reached the pre-specified target, which was DAS28 remission (<2.6) for 112 (43.2%) patients and LDA (<3.2) for 63 (24.3%) patients. Factors that negatively impacted the target achievement were fibromyalgia (HR: 0.2 [0.05-0.81]), HAQ-DI (HR: 0.72 [0.56-0.93]) and ESR (HR: 0.99 [0.99-1]). Globally, 33 (12.7%) patients started a biologic DMARD, while 61 out of 84 (72.6%) patients who had never reached the target remained on conventional DMARD. One-hundred and ninety-three adverse events (AEs) were recorded, the majority classified as mild (91 cases, 51%). CONCLUSIONS: A high proportion of RA patients achieved the target during the first-year follow-up. However, a considerable portion of RA patients did not start a biological drug although the target was never reached. AEs remain frequent with conventional DMARDs, but the majority were mild.
35445144 Connective tissue disease-related interstitial lung disease (CTD-ILD) and interstitial lun 2022 Connective tissue diseases (CTDs) demonstrating features of interstitial lung disease (ILD) include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), dermatomyositis (DM) and polymyositis (PM), ankylosing spondylitis (AS), Sjogren syndrome (SS), and mixed connective tissue disease (MCTD). On histopathology of lung biopsy in CTD-related ILDs (CTD-ILDs), multi-compartment involvement is an important clue, and when present, should bring CTD to the top of the list of etiologic differential diagnoses. Diverse histologic patterns including nonspecific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), organizing pneumonia, apical fibrosis, diffuse alveolar damage, and lymphoid interstitial pneumonia can be seen on histology in patients with CTD-ILDs. Although proportions of ILDs vary, the NSIP pattern accounts for a large proportion, especially in SSc, DM and/or PM and MCTD, followed by the UIP pattern. In RA patients, interstitial lung abnormality (ILA) is reported to occur in approximately 20-60% of individuals of which 35-45% will have progression of the CT abnormality. Subpleural distribution and greater baseline ILA involvement are risk factors associated with disease progression. Asymptomatic CTD-ILDs or ILA patients with normal lung function and without evidence of disease progression can be followed without treatment. Immunosuppressive or antifibrotic agents for symptomatic and/or fibrosing CTD-ILDs can be used in patients who require treatment.
35259476 Lifetime female hormonal exposure and risk of rheumatoid arthritis in postmenopausal women 2022 Mar 5 OBJECTIVE: To assess the relationships between lifetime female hormonal exposures and the risk of incident RA in postmenopausal women. METHODS: E3N is an ongoing French prospective cohort of 98,995 women since 1990 aged 40-65 years at enrolment. Data on reproductive/hormonal factors and treatments were regularly recorded. Exposures were defined as follows: - reproductive span (in years)=duration from menarche to menopause; - total ovulatory years=reproductive span-(number of full-term pregnancies×0.75+number of miscarriages×0.25+total duration of breast feeding+total duration of oral contraception); - lifetime duration of hormonal exposure (in years)=reproductive span+total duration of menopausal hormonal therapy; - composite estrogen score (CES, range=0-6): 1 point for each item: early menarche, high parity, history of hysterectomy, use of oral contraception, use of menopausal hormonal therapy and late menopause. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of incident RA were estimated using Cox proportional hazards regression models with age as the time scale. RESULTS: Among the 78,391 postmenopausal cohort women, 637 validated incident RA cases occurred. Lifetime durations of hormonal exposures were not associated with incident RA in postmenopausal women. High (CES=4-6) versus low (CES=0-1) estrogen exposure was inversely associated with the risk of RA: HR 0.37; 95% CI 0.2-0.8. CONCLUSION: In the E3N cohort, high lifetime estrogen exposure, that summarizes cumulative endogenous and exogenous exposures, was associated with a decreased risk of RA in postmenopausal women.
33307184 Long-term Outcomes Following Multiply Recurrent Clostridioides difficile Infection and Fec 2022 Apr BACKGROUND AND AIMS: Fecal microbiota transplantation (FMT) is a commonly used therapy for multiply recurrent Clostridioides difficile (mrCDI). By altering the gut microbiota, there is the potential for FMT to impact the risk for cardiometabolic, intestinal or immune-mediated conditions. Likewise, the microbiota disturbance associated with mrCDI could potentially lead to these conditions. We aimed to assess the associations of mrCDI and FMT with cardiometabolic, immune-mediated diseases, and irritable bowel syndrome. METHODS: This retrospective cohort study using a United States commercial claims database included persons diagnosed with CDI or undergoing FMT. We created 2 pairwise comparisons: mrCDI vs non-mrCDI, and non-mrCDI or mrCDI treated with FMT vs mrCDI without FMT. RESULTS: We found no significant association between mrCDI (vs non-mrCDI) and inflammatory bowel disease (adjusted hazard ratio (aHR) = 1.65; 95% confidence interval, 0.67-4.04), rheumatoid arthritis (HR = 0.86; 0.47-1.56), psoriasis (HR = 0.72; 0.23-2.27), diabetes (aHR = 0.97; 0.67-1.40), hypertension (aHR = 1.05; 0.76-1.44), myocardial infarction (aHR = 0.82; 0.63-1.06), stroke (aHR = 0.83; 0.62-1.12), or irritable bowel syndrome (HR = 0.94; 0.61-1.45). Similarly, we found no association of CDI with FMT (vs mrCDI without FMT) and diabetes (aHR = 0.92; 0.27-3.11), hypertension (aHR = 1.41; 0.64-3.15), stroke (aHR = 1.27; 0.69-2.34) or inflammatory bowel syndrome (aHR = 0.80; 0.26-2.46). However, the incidence of myocardial infarction was increased following FMT (aHR = 1.68; 1.01-2.81). CONCLUSION: Relative to those with CDI, persons with mrCDI do not appear to be intrinsically at higher risk of cardiometabolic, immune-mediated diseases, or irritable bowel syndrome. However, those who underwent FMT for CDI had a higher incidence of myocardial infarction. Future studies should assess this association to assess reproducibility.
35579773 Implementation of the treat-to-target approach and treatment satisfaction in patients with 2022 May 17 OBJECTIVE: To investigate the implementation of treat-to-target (T2T) and treatment satisfaction from Chinese rheumatologists' perspectives. METHODS: This retrospective analysis of a cross-sectional database collected from rheumatologists and their adult patients with RA in China using Adelphi Real World Disease Specific Programme™ methodology. Multivariate logistic regression models were used to evaluate factors associated with T2T use, achievement of T2T goals, and physician treatment satisfaction. RESULTS: Sixty physicians provided data for 600 patients, of whom 39.0% (234/600) were being treated using T2T, and 64.9% (366/564) had achieved their T2T goal. Physicians were satisfied with treatment in 74.3% (445/599) of patients. Patients with a higher pain score were more likely to be managed using T2T (odds ratio (OR) 1.25; p = 0.017), but less likely to have achieved the T2T goal (OR 0.76; p = 0.004). T2T use was more likely if patients had a longer time since diagnosis (> 2 vs ≤ 2 years; OR 1.61; p = 0.031) or received targeted synthetic or biologic disease-modifying antirheumatic drugs (tsDMARDs or bDMARDs; OR 6.90; p < 0.001). T2T goal achievement was more likely for patients with higher body mass index (≥ 24 vs < 24 kg/m(2); OR 2.73; p = 0.001) or full-time employment (OR 2.11; p = 0.005). Physician treatment satisfaction was more likely if the T2T goal was achieved (OR 4.78; p < 0.001) or tsDMARDs or bDMARDs were used (OR 2.58; p = 0.017), and less likely if pain scores were higher (OR 0.79; p = 0.019). CONCLUSIONS: T2T implementation in China is suboptimal. Our findings provide insight into T2T implementation and physician treatment satisfaction, supporting T2T use in Chinese RA clinical practice. Key Points • T2T implementation in China is currently suboptimal. • Patients with greater pain were more likely to be managed using T2T but were less likely to have achieved their T2T goals. • Physician treatment satisfaction was associated with T2T goal achievement.
34626797 Administration of an adeno-associated viral vector expressing interferon-β in patients wi 2022 Jan OBJECTIVE: Inflammatory hand arthritis (IHA) results in impaired function. Local gene therapy with ART-I02, a recombinant adeno-associated virus (AAV) serotype 5 vector expressing interferon (IFN)-β, under the transcriptional control of nuclear factor κ-B responsive promoter, was preclinically shown to have favorable effects. This study aimed to investigate the safety and tolerability of local gene therapy with ART-I02 in patients with IHA. METHODS: In this first-in-human, dose-escalating, cohort study, 12 IHA patients were to receive a single intra-articular (IA) injection of ART-I02 ranging 0.3 × 10(12)-1.2 × 10(13) genome copies in an affected hand joint. Adverse events (AEs), routine safety laboratory and the clinical course of disease were periodically evaluated. Baseline- and follow-up contrast enhanced magnetic resonance images (MRIs), shedding of viral vectors in bodily fluids, and AAV5 and IFN-β immune responses were evaluated. A data review committee provided safety recommendations. RESULTS: Four patients were enrolled. Long-lasting local AEs were observed in 3 patients upon IA injection of ART-I02. The AEs were moderate in severity and could be treated conservative. Given the duration of the AEs and their possible or probable relation to ART-I02, no additional patients were enrolled. No systemic treatment emergent AEs were observed. The MRIs reflected the AEs by (peri)arthritis. No T-cell response against AAV5 or IFN-β, nor IFN-β antibodies could be detected. Neutralizing antibody titers against AAV5 raised post-dose. CONCLUSION: Single IA doses of 0.6 × 10(12) or 1.2 × 10(12) ART-I02 vector genomes were administered without systemic side effects or serious AEs. However, local tolerability was insufficient for continuation. TRIAL REGISTRATION: NCT02727764.
34977434 Instructive cartilage regeneration modalities with advanced therapeutic implantations unde 2022 May The development of interdisciplinary biomedical engineering brings significant breakthroughs to the field of cartilage regeneration. However, cartilage defects are considerably more complicated in clinical conditions, especially when injuries occur at specific sites (e.g., osteochondral tissue, growth plate, and weight-bearing area) or under inflammatory microenvironments (e.g., osteoarthritis and rheumatoid arthritis). Therapeutic implantations, including advanced scaffolds, developed growth factors, and various cells alone or in combination currently used to treat cartilage lesions, address cartilage regeneration under abnormal conditions. This review summarizes the strategies for cartilage regeneration at particular sites and pathological microenvironment regulation and discusses the challenges and opportunities for clinical transformation.
35649544 Canadian Rheumatology Association Meeting Virtual Conference, February 2-5, 2022. 2022 Jun 1 The 76th Annual Meeting of the Canadian Rheumatology Association was held virtually on February 2-5, 2022. The program consisted of presentations covering original research, symposia, awards, and lectures. Highlights of the meeting include the following 2022 Award Winners: Distinguished Rheumatologist, John G. Hanly and Lori B. Tucker; Distinguished Teacher- Educator, Stephen Aaron; Emerging Investigator, Jessica Widdifield; Ian Watson Award for the Best Abstract on SLE Research by a Trainee, Maher Banjari; Phil Rosen Award for the Best Abstract on Clinical or Epidemiology Research by a Trainee, Molly Dushnicky; Best Abstract by a Rheumatology Resident, Wen Qi; Best Abstract on Basic Science Research by a Trainee, Omar Cruz Correa; Best Abstract by a Post-Graduate Research Trainee, Holly Philpott; Best Abstract on Quality Care Initiatives in Rheumatology, Michael Zeeman; Best Abstract by a Medical Student, Samir Magdy Iskander; Best Abstract by an Undergraduate Student, Daniel Onwuka; Best Abstract by a Rheumatology Post-Graduate Research Trainee, Jennifer Lee; Best Abstract on Research by Young Faculty, Nancy Maltez; Best Abstract on Pediatric Research by Young Faculty, Chelsea DeCoste; Best Abstract on Spondyloarthritis Research, Vanessa Ocampo; Practice Reflection Award, Gold, Bailey Dyck. Lectures and other events included: Keynote Lecture by Grace Wright: Towards Equity: Is Everyone in the Rheum Paving the Path to Equity with Diversity?; State of the Art Lecture by Tuhina Neogi: Pain Across the Spectrum of Rheumatic Diseases; Dunlop-Dottridge Lecture by Simon Carette: Vasculitis: What Have We Learned in the Past 50 Years?; and the Great Debate: Be it Resolved that the Rheumatology Healthcare Provider Is Responsible for Prescribing and Monitoring Physical Activity. Arguing for: Claire LeBlanc and Laura Passalent, and against: Arthur Bookman and Marie Clements-Baker. Topics including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjögren syndrome, psoriatic arthritis, spondyloarthritis, vasculitis, osteoarthritis, fibromyalgia, and their respective diagnoses, treatments, and outcomes are reflected in the abstracts, which we are pleased to publish in this issue of The Journal of Rheumatology.
35588095 Identification of Multimorbidity Patterns in Rheumatoid Arthritis through Machine Learning 2022 May 19 OBJECTIVE: Recognizing that the interrelationships between chronic conditions that complicate rheumatoid arthritis (RA) are poorly understood, we aimed to identify patterns of multimorbidity and to define their prevalence in RA through machine learning. METHODS: We constructed RA and age- and gender-matched (1:1) non-RA cohorts within a large commercial insurance database (MarketScan®) and the Veterans Health Administration (VHA). Chronic conditions (n=44) were identified from diagnosis codes from outpatient and inpatient encounters. Exploratory factor analysis was performed separately in both databases, stratified by RA diagnosis and sex, to identify multimorbidity patterns. The association of RA with different multimorbidity patterns was determined using conditional logistic regression. RESULTS: We studied 226,850 patients in MarketScan® (76% female) and 120,780 patients in the VHA (89% male). The primary multimorbidity patterns identified were characterized by the presence of cardiopulmonary, cardiometabolic, and mental health and chronic pain disorders. Multimorbidity patterns were similar between RA and non-RA patients, females and males, MarketScan® and the VHA. RA patients had higher odds of each multimorbidity pattern (odds ratios [ORs] 1.17 to 2.96), with mental health and chronic pain disorders being the multimorbidity pattern most strongly associated with RA (ORs 2.07 to 2.96). CONCLUSIONS: Cardiopulmonary, cardiometabolic, and mental health and chronic pain disorders represent predominant multimorbidity patterns, each of which are over-represented in RA. The identification of multimorbidity patterns occurring more frequently in RA is an important first step in progressing toward a holistic approach to RA management and warrants assessment of their clinical and predictive utility.
35040282 Association of Healthy Lifestyle Behaviors and the Risk of Developing Rheumatoid Arthritis 2022 Jan 18 OBJECTIVE: We investigated whether a healthy lifestyle, defined by a healthy lifestyle index score (HLIS), was associated with rheumatoid arthritis (RA) risk, overall and seropositive/seronegative subtypes. METHODS: We analyzed female nurses in Nurses' Health Study (NHS, 1986-2016) and NHSII (1991-2017). Lifestyle and medical information were collected on biennial questionnaires. Medical records confirmed incident RA and serostatus. The HLIS index includes five modifiable components: smoking, alcohol consumption, body mass index, physical activity, and diet. Cox regression, adjusted for confounders, modeled associations between HLIS and incident RA. The population attributable risk (PAR) estimated the proportion of incident RA preventable if participants adopted ≥4 healthy lifestyle factors. RESULTS: 1,219 incident RA cases (776 seropositive; 443 seronegative) developed in 4,467,751person-years. Higher (healthier) HLIS was associated with lower overall (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.82-0.90), seropositive (HR 0.85, 95% CI 0.80-0.91), and seronegative RA risk (HR 0.87, 95% 0.80-0.94). Women with 5 healthy lifestyle factors had lowest risk (HR 0.42, 95% CI 0.22-0.80). The PAR for adhering to ≥ 4 lifestyle factors was 34% for RA. CONCLUSION: In this prospective cohort, healthier lifestyle was associated with lower RA risk. A substantial proportion of RA may be preventable by healthy lifestyle.