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33191276 Priorities for High-quality Care in Rheumatoid Arthritis: Results of Patient, Health Profe 2021 Apr OBJECTIVE: To elucidate the essential elements of high-quality rheumatoid arthritis (RA) care in order to develop a vision statement and a set of strategic objectives for a national RA quality framework. METHODS: Focus groups and interviews were conducted by experienced qualitative researchers using a semistructured interview or focus group guide with healthcare professionals, patients, clinic managers, healthcare leaders, and policy makers to obtain their perspectives on elements essential to RA care. Purposive sampling provided representation of stakeholder types and regions. Recorded data was transcribed verbatim. Two teams of 2 coders independently analyzed the deidentified transcripts using thematic analysis. Strategic objectives and the vision statement were drafted based on the overarching themes from the qualitative analysis and finalized by a working group. RESULTS: A total of 54 stakeholders from 9 Canadian provinces participated in the project (3 focus groups and 19 interviews). Seven strategic objectives were derived from the qualitative analysis representing the following themes: (1) early access and timeliness of care; (2) evidence-informed, high-quality care for the ongoing management of RA and comorbidities; (3) availability of patient self-management tools and educational materials for shared decision making; (4) multidisciplinary care; (5) patient outcomes; (6) patient experience and satisfaction with care; and (7) equity, the last of which emerged as an overarching theme. The ultimate vision obtained was "ensuring patient-centered, high-quality care for people living with rheumatoid arthritis." CONCLUSION: The 7 strategic objectives that were identified highlight priorities for RA quality of care to be used in developing the National RA Quality Measurement Framework.
33535081 Circ_AFF2 facilitates proliferation and inflammatory response of fibroblast-like synoviocy 2021 Apr Circular RNAs (circRNAs) have been implicated in the pathological regulation of human diseases by acting as microRNA (miRNA) sponges to affect gene expression. CircRNA Fragile Mental Retardation 2 (circ_AFF2) was dysregulated in rheumatoid arthritis (RA), but little is known about its specific function and hidden molecular mechanism in RA. Circ_AFF2, miR-375 and TAK1-binding 2 (TAB2) expression levels were determined through the quantitative real-time polymerase chain reaction (qRT-PCR). Flow cytometry was performed to analyze cell cycle and apoptosis. Cell proliferation detection was conducted by 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The protein levels were measured using western blot. Inflammatory response was evaluated by enzyme-linked immunosorbent assay (ELISA). RNA pull-down assay was used to select the miRNA target of circ_AFF2. The interaction between miR-375 and circ_AFF2 or TAB2 was analyzed using the dual-luciferase reporter assay. Contrasted to normal samples and fibroblast-like synoviocytes (FLS), circ_AFF2 expression was upregulated in RA blood samples and FLS-RA cells. Cell cycle, proliferation and inflammatory response were blocked while apoptosis was promoted in FLS-RA after the downregulation of circ_AFF2. In addition, circ_AFF2 could interact with miR-375 and the function of circ_AFF2 was achieved by sponging miR-375 in FLS-RA cells. Moreover, TAB2 was a target of miR-375 and miR-375 repressed RA progression by decreasing TAB2 expression in FLS-RA cells. More importantly, circ_AFF2 promoted the expression of TAB2 by targeting miR-375. These findings clarified that circ_AFF2 induced cell progression, inflammatory response in FLS-RA cells via the miR-375/TAB2 axis. Circ_AFF2 could be used as a biomarker in the diagnosis and treatment of RA.
34599044 Risk of 30-day Readmission After Knee or Hip Replacement in Rheumatoid Arthritis and Osteo 2022 Feb OBJECTIVE: To determine the indication and risk of 30-day rehospitalization after hip or knee replacement among patients with rheumatoid arthritis (RA) and osteoarthritis (OA) by Medicare and non-Medicare status. METHODS: Using the Nationwide Readmission Database (2010-2014), we defined an index hospitalization as an elective hospitalization with a principal procedure of total hip (THR) or knee replacement (TKR) among adults aged ≥ 18 years. Primary payer was categorized as Medicare or non-Medicare. Survey logistic regression provided the odds of 30-day rehospitalization in RA relative to OA. We calculated the rates for principal diagnoses leading to rehospitalization. RESULTS: Overall, 3.53% of 2,190,745 index hospitalization had a 30-day rehospitalization. Patients with RA had a higher adjusted risk of rehospitalization after TKR (OR 1.11, 95% CI 1.02-1.21) and THR (OR 1.39, 95% CI 1.19-1.62). Persons with RA and OA did not differ with respect to rates of infections, cardiac events, or postoperative complications leading to the rehospitalization. After TKR, RA patients with Medicare had a lower venous thromboembolism (VTE) risk (OR 0.58, 95% CI 0.58-0.88), whereas those with RA had a greater VTE risk (OR 2.41, 95% CI 1.04-5.57) after THR. CONCLUSION: Patients with RA had a higher 30-day rehospitalization risk than OA after TKR and THR regardless of payer type. While infections, postoperative complications, and cardiac events did not differ, there was a significant difference in VTE as the principal diagnosis of rehospitalization.
34952630 CTLA4-Ig treatment induces M1-M2 shift in cultured monocyte-derived macrophages from healt 2021 Dec 24 BACKGROUND: In rheumatoid arthritis (RA), macrophages play an important role in modulating the immunoinflammatory response through their polarisation into "classically" (M1) or "alternatively activated" (M2) phenotypes. In RA, CTLA4-Ig (abatacept) reduces the inflammatory activity of macrophages by interacting with the costimulatory molecule CD86. The study aimed to investigate the efficacy of CTLA4-Ig treatment to induce an M2 phenotype both in M1-polarised monocyte-derived macrophages (MDMs) obtained from healthy subjects (HS) and in cultured MDMs obtained from active RA patients. METHODS: Cultured MDMs were obtained from peripheral blood mononuclear cells of 7 active RA patients and from 10 HS after stimulation with phorbol myristate acetate (5 ng/mL) for 24 h. HS-MDMs were then stimulated with lipopolysaccharide (LPS, 1 mg/mL) for 4 h to induce M1-MDMs. M1-MDMs and RA-MDMs were treated with CTLA4-Ig (100 μM and 500 μM) for 3, 12, 24, and 48 h. The gene expression of CD80, CD86, and TLR4 (M1 markers); CD163, CD204, and CD206 (surface M2 markers); and MerTK (functional M2 marker) was evaluated by qRT-PCR. The protein synthesis of surface M2 markers was investigated by Western blotting. The statistical analysis was performed by the Wilcoxon t-test. RESULTS: In LPS-induced HS-M1-MDMs, CTLA4-Ig 100 μM and 500 μM significantly downregulated the gene expression of M1 markers (3 h p<0.01 for all molecules; 12 h p<0.05 for TLR4 and CD86) and significantly upregulated that of M2 markers, primarily after 12 h of treatment (CD163: p < 0.01 and p < 0.05; CD206: p < 0.05 and p < 0.01; CD204: p < 0.05 by 100 mg/mL). Moreover, in these cells, CTLA4-Ig 500 μM increased the protein synthesis of surface M2 markers (p < 0.05). Similarly, in RA-MDMs, the CTLA4-Ig treatment significantly downregulated the gene expression of M1 markers at both concentrations primarily after 12 h (p < 0.05). Furthermore, both concentrations of CTLA4-Ig significantly upregulated the gene expression of CD206 (after 3 h of treatment; p < 0.05), CD163, and MerTK (after 12 h of treatment, p < 0.05), whereas CD204 gene expression was significantly upregulated by the high concentration of CTLA4-Ig (p < 0.05). The protein synthesis of all surface markers was increased primarily by CTLA4-Ig 500 μM, significantly for CD204 and CD206 after 24 h of treatment (p < 0.05). CONCLUSIONS: CTLA4-Ig treatment seems to induce the in vitro shift from M1 to M2 macrophages, of both HS-M1-MDMs and RA-MDMs, as observed by the significant downregulation exerted on selected M1 markers and the upregulation of selected M2 markers suggesting an additional mechanism for its modulation of the RA inflammatory process.
34103319 Bidirectional association between migraine and rheumatoid arthritis: two longitudinal foll 2021 Jun 8 OBJECTIVE: To investigate the bidirectional association between migraine and rheumatoid arthritis (RA). DESIGN: Two longitudinal follow-up studies. SETTING: Data collected from a national cohort between 2002 and 2013 by the Korean National Health Insurance Service-Health Screening Cohort. PARTICIPANTS: In cohort 1, matching resulted in the inclusion of 31 589 migraine patients and 126 356 control I participants. In cohort 2, matching resulted in the inclusion of 9287 RA patients and 37 148 control II participants. PRIMARY AND SECONDARY OUTCOME MEASURES: The HRs for RA in patients with migraine (cohort 1) and migraine in patients with RA (cohort 2) were analysed using stratified Cox proportional hazard models after adjusting for autoimmune disease, Charlson Comorbidity Index scores without rheumatoid diseases, obesity (body mass index), smoking and history of alcohol intake. Subgroup analyses stratified by age, sex, income and region of residence were also performed. RESULTS: The incidence of RA in the migraine group (2.0% (640/31 589)) was higher than that in the control I group (1.4% (1709/126 356), p<0.001). The adjusted HR for RA in the migraine without aura group was 1.48 (95% CIs=1.34 to 1.63, p<0.001).The incidence of migraine in the RA group (6.4% (590/9287)) was higher than that in the control II group (4.6% (1721/37 148), p<0.001). The adjusted HR for migraine without aura in the RA group was 1.35 (95% CI=1.23 to 1.49, p<0.001). CONCLUSION: Migraine increases the risk of RA, and RA is also associated with an increased risk of migraine.
34855107 The current status of anti-citrullinated protein antibodies and citrullinated protein-reac 2022 Mar Anti-citrullinated protein antibodies are a hallmark of rheumatoid arthritis. It is widely acknowledged that the presence of ACPAs is the result of the interaction of genes, the environment and epigenetic modifications. The mechanism by which the factors, especially citrullination and ACPA glycosylation, affect ACPAs is still unclear. In this article, we review the presence of the ACPAs in RA and their relationship with clinical manifestations. The pathogenicity of ACPAs and B cells in RA was also summarized. A growing body of evidence has shown that ACPA-positive patients have more serious bone erosion and destruction and poor clinical prognosis than ACPA-negative patients. Recently, with the direct study of citrullinated protein-reactive B cells, their role in the development of rheumatoid arthritis has been further understood. It indicates that further understanding of the mechanism of ACPAs and CP-reactive B cells would beneficial in the prevention and treatment of RA.
34644014 [Consequences of antinuclear antibodies testing in clinical practice]. 2021 Oct 13 Connectivitis or collagenosis are autoimmune multi-systemic diseases. Systemic lupus erythematous (SLE) and Sjogren's syndrome are the most common type after the rheumatoid arthritis. Antinuclear antibodies (ANA), previously called antinuclear factors, are frequently present in connectivitis. Due to their high sensitivity, they may constitute a good screening test. To avoid useless and expensive investigations following a false positive test, a high clinical suspicion is required before any further biological testing. In case of ANA positive testing and low clinical evidence, the presence of anti-DSF70 antibody enables to exclude the diagnostics with a good negative predictive value.
34192347 DPP4 reduces proinflammatory cytokine production in human rheumatoid arthritis synovial fi 2021 Dec Rheumatoid arthritis (RA) is an autoimmune disorder that is characterized by increasing levels of proinflammatory cytokines. The ubiquitous enzyme dipeptidyl peptidase-4 (DPP4, also known as CD26) regulates different immune disorders, although the effects of DPP4 in RA are uncertain. Here, we found lower levels of DPP4 in RA synovial tissues compared with normal tissues. DPP4 levels were also lower in a rat collagen-induced arthritis model than in control (healthy) rats. Overexpression of DPP4 or exogenous treatment of RA synovial fibroblasts with DPP4 reduced levels of proinflammatory interleukin (IL)-1β, IL-6, and IL-13, and increased anti-inflammatory IL-10 synthesis, while DPP4 inhibitors sitagliptin and vildagliptin increased proinflammatory cytokine production, indicating an enhanced risk of RA development. The evidence suggests that increasing DPP4 expression is a novel strategy for RA disease.
32888273 Pulmonary Manifestations of Rheumatoid Arthritis, Psoriatic Arthritis and Peripheral Spond 2021 Interstitial lung disease (ILD) is the most common form of pulmonary impairment in patients with rheumatoid arthritis (RA). However, patients with RA or other arthritic diseases such as psoriatic arthritis (PsA) or peripheral spondyloarthritis (pSpA) are at a higher risk of developing several other pulmonary diseases, such as chronic obstructive lung disease (COPD), compared to patients without arthritis. This review aims at summarizing the current knowledge on the prevalence of pulmonary diseases in the above-mentioned forms of arthritis, the challenges faced by prevalence studies in detecting pulmonary diseases in patients with arthritis, as well as possible treatment options. Dyspnea, cough or other pulmonary symptoms in arthritis patients should prompt gradual diagnostic procedures considering pulmonary manifestations as a major cluster of differential diagnosis. However, treatment options often lack solid evidence-based guidelines and referrals to specialized centers are often necessary.
33645133 [Effect of Xinfeng Capsules-containing serum on TNF-α-induced apoptosis and inflammation 2021 Jan The aim of this paper was to observe the effect of Xinfeng Capsules(XFC)-containing serum on the apoptosis and inflammation of fibroblast-like synoviocytes(FLS) in rheumatoid arthritis(RA) induced by tumor necrosis factor-α(TNF-α), so as to investigate the mechanism of XFC in the treatment of RA. RA-FLS immortalized cell line was established, and XFC drug-containing serum was prepared. CCK-8, ELISA, RT-qPCR, immunofluorescence and TUNEL were used to observe the effect of XFC-containing serum on RA-FLS apoptosis and inflammatory indexes. CCK-8 results showed that the optimal concentration and time of TNF-α on RA-FLS were 10 ng·mL~(-1) and 48 h, respectively; and the optimal concentration and time of XFC on RA-FLS were 6.48 mg·g~(-1) and 72 h, respectively. The results of ELISA showed that compared with RA-FLS group, the expressions of TNF-α, IL-1β, IL-6, IL-8 in TNF-α+RA-FLS group were significantly increased, while the expressions of IL-4 and IL-10 were significantly decreased(P<0.01); after intervention with XFC-containing serum, the expressions of TNF-α, IL-1β, IL-6, IL-8 were significantly decreased, whereas the expressions of IL-4 and IL-10 were significantly increased(P<0.01). The results of RT-qPCR showed that compared with RA-FLS group, the mRNA expressions of Fas, FasL, caspase-3, caspase-8, Bax, Bcl-X1 in TNF-α+RA-FLS group were significantly decreased, while the mRNA expression of Bcl-2 was significantly increased(P<0.001); after intervention with XFC-containing serum, the mRNA expressions of Fas, FasL, caspase-3, caspase-8, Bax, Bcl-X1 were significantly increased, whereas the mRNA expression of Bcl-2 was significantly decreased(P<0.01). The results of immunofluorescence showed that compared with RA-FLS group, the protein expressions of caspase-3 and Bax in TNF-α+RA-FLS group was significantly lower than those in RA-FLS group(P<0.05); after intervention with XFC-containing serum, the protein expressions of caspase-3 and Bax were significantly increased, whereas the protein expression of Bcl-2 was significantly decreased(P<0.05). TUNEL results showed that compared with RA-FLS group, the apoptosis of TNF-α+RA-FLS group was decreased(P<0.05); after intervention with XFC-containing serum, the apoptosis was significantly increased(P<0.05). One of the mechanisms of XFC in the treatment of RA is to promote the apoptosis of RA-FLS and inhibit its inflammatory reaction.
34362418 Is tea consumption associated with reduction of risk of rheumatoid arthritis? A Swedish ca 2021 Aug 7 BACKGROUND: Tea is a popular beverage around the world and has properties that can affect the immune system. The association between tea consumption and the risk of rheumatoid arthritis (RA), a chronic autoimmune disease primarily affecting the joints, is not well studied and results are conflicting. METHODS: We collected data on tea consumption for 2237 incident RA cases diagnosed 2005-2018 and 4661 controls matched on age, sex, and residential area. Tea consumption was classified into no (0 cups/day), irregular (< 1 cup/day), regular (1-2 cups/day), and high (≥ 2 cups/day) consumption, and irregular consumption was used as the reference category. Missing data on tea consumption was classified as no consumers, and sensitivity analyses were performed to test this assumption. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression, adjusting for smoking, coffee, alcohol, educational level, and body mass index. We also performed stratified analysis on sex, anti-citrullinated autoantibody (ACPA) status, and smoking habits. RESULTS: Among the cases, we found 57.3% to be ever consumers of tea with 19.7 having a high tea consumption. Corresponding figures for the controls were 58.4% ever drinkers with 22.1% high tea consumers. High tea consumption had an inverse association to the risk of RA compared to irregular consumption [OR = 0.78 (95% CI 0.66-0.92)], but the association lost statistical significance in the adjusted model [adjusted OR (adjOR) = 0.85 (95% CI 0.71-1.01)]. Among non-tea consumers, a protective effect was also observed compared to irregular consumers [adjOR = 0.82 (95% CI 0.70-0.88)], but this association did not withstand sensitivity analysis, possibly due to bias. In the ACPA-positive group and among current smokers, a protective effect of tea consumption was observed among the high tea consumers [adjOR = 0.76 (95% CI 0.62-0.94) and adjOR = 0.60 (95% CI 0.38-0.95), respectively]. CONCLUSIONS: This study suggests a protective effect of high consumption of tea, among smokers and for ACPA-positive RA. TRIAL REGISTRATION: Not applicable.
32876784 Systematic review of recommendations on the use of methotrexate in rheumatoid arthritis. 2021 Apr OBJECTIVE: Most recommendations for the use of methotrexate (MTX) in rheumatoid arthritis (RA) are issued by developed countries. It is unknown whether they are relevant globally. We reviewed existing recommendations on the use of MTX for the treatment of RA and summarized areas of agreement that could be relevant for least developed countries (LDCs). METHODS: Electronic databases and registries were searched for recommendations on MTX use in RA, duplicates were eliminated, and the most updated version adopted when there were several versions on the same recommendation. Reviewers used the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument for study quality assessment. Similarities and discrepancies of recommendations are reported. RESULTS: After deduplication, 1693 unique citations were found; 25 full texts were screened and 12 included in the narrative synthesis. Average scores for the AGREE II domains ranged from 33.3 to 83.3%. Recommendations targeted rheumatologists and health care providers involved in RA care. Most covered some but not all of the following areas: baseline "pre-MTX" assessment (7/12;58%), prescription of MTX (10/12;83.3%), management of MTX side effects (6/12;50%), and special considerations (e.g., peri-operative management) (8/12; 66.7%). Recommendations agreed on baseline tests prior to starting MTX, monitoring, and need for folic acid supplementation. These aspects can serve as the foundation for the development of MTX recommendations relevant to LDCs. Recommendations disagreed on the MTX starting dose, optimal route, titration, and intervals to monitor toxicity. CONCLUSION: Existing recommendations do not uniformly address all aspects related to the use of MTX and disagree in relevant aspects of MTX use. Adaptations to these recommendations are needed to facilitate their implementation in LDCs. Key Points • This paper summarizes current recommendations on the use of methotrexate for the treatment of rheumatoid arthritis. • Areas of agreement between recommendations include the following: pre-methotrexate patient assessment, need for folic acid supplementation, and toxicity monitoring. • Areas of disagreement relate to methotrexate starting and maximal dose, titration, and frequency of assessments.
32506315 Patient-provider communication about medication cost in rheumatoid arthritis. 2021 Jan OBJECTIVE: To examine the perceived importance and frequency with which out-of-pocket medication costs are discussed between rheumatologists and patients with rheumatoid arthritis (RA) in Canada. METHODS: A cross-sectional online survey was distributed to patients with RA and rheumatologists; both were asked to rate their perceived importance of discussing medication costs, and how often these discussions occurred. Predictors of (1) patients discussing costs with their rheumatologist and (2) the perceived importance of discussing medication cost for patients were explored. RESULTS: Seventy-eight patients and 64 rheumatologists completed the survey; 68% patients and 75% of physicians rated the perceived importance of discussing medication costs as "quite" or "very important"; 22% of patients reported never talking about medication cost, but no physicians reported never discussing costs with patients. The only predictor of talking about cost among patients (at 10% level) was whether they perceived it as highly important (p = 0.058). Higher perceived importance of discussing out-of-pocket costs was associated with a more positive attitude to shared decision-making (p = 0.044). CONCLUSION: Discussions about cost do not always happen, even with diseases with potentially high medication costs like RA. Cost was more likely to be discussed by patients who perceived it as "very important," suggesting the onus might be on patients to initiate these conversations. Without any significant predictors regarding what may make physicians more likely to think it was important to discuss medication costs, there is a need to reinforce recommendations that all physicians seek to discuss costs with all of their patients when suggesting medications. Key Points • There is a need for patients and physicians to discuss costs in the treatment decision-making process. Our findings suggest this does not always happen. • Among patients, medication cost was more likely to be discussed by those who perceived it as "very important" and higher perceived importance of discussing out-of-pocket costs was associated with a more positive attitude to shared decision-making. • Our results did not reveal any significant predictors regarding what may make physicians more likely to think it was important to discuss medication costs, suggesting that there is a need to reinforce recommendations that all physicians seek to discuss medication costs with all of their patients when suggesting medications.
34739327 Neuropsychiatric adverse drug reactions associated with low dose methotrexate in rheumatoi 2022 Mar BACKGROUND: Neuropsychiatric adverse drug reactions (NPADRs) are not commonly associated with low dose methotrexate (LDMTX) in patients with rheumatoid arthritis (RA). RESEARCH DESIGN AND METHODS: In this case series assessment, we described the nature and frequency of NPADRs with LDMTX in the Dutch DREAM-RA registry, including causality of NPADRs, the impact on further LDMTX treatment and the impact on patient reported Health Related Quality of Life (HRQoL). RESULTS: A total of 71 NPADRs (frequency 6.8%) associated with LDMTX were captured in the DREAM-RA registry. NPADRs were registered for 62 (5.9%) out of 1048 patients with 10.9 NPADRs per 1000 patient years. Headache, dizziness and depression were most frequently reported. The causality was considered probable for 67 NPADRs (94.4%) and definite for 1 NPADR (1.4%). NPADRs led to LDMTX withdrawal in 34 cases (47.9%) and was not restarted in 16 cases (47.1%). Median mental HRQoL was significantly decreased around the occurrence of the NPADR and remained significantly lower after the event. Median physical HRQoL was not significantly affected. CONCLUSIONS: Knowledge on the nature, frequency and impact of the demonstrated NPADRs during LDMTX therapy will enhance attention toward these potential ADRs allowing better risk assessment and communication to patients.
33338001 Efficacy and safety of baricitinib in 446 patients with rheumatoid arthritis: a real-life 2021 Jul OBJECTIVES: Baricitinib, an oral Janus kinase (JAK) 1-2 inhibitor, is currently used along biologic DMARDs (bDMARDs) after the failure of methotrexate (MTX) in rheumatoid arthritis (RA). We investigated the efficacy and safety of baricitinib in real life. METHODS: We prospectively enrolled 446 RA patients treated with baricitinib from 11 Italian centres. Patients were evaluated at baseline and after 3, 6, and 12 months. They were arrayed based on previous treatments as bDMARD-naïve and bDMARD-insufficient responders (IR) after the failure or intolerance to bDMARDs. A sub-analysis differentiated the effects of methotrexate (MTX) and the use of oral glucocorticoids (OGC). RESULTS: Our cohort included 150 (34%) bDMARD-naïve and 296 (66%) bDMARD-IR patients, with 217 (49%) using baricitinib as monotherapy. Considering DAS-28-CRP as the primary outcome, at 3 and 6 months, 114/314 (36%) and 149/289 (51.6%) patients achieved remission, while those in low disease activity (LDA) were 62/314 (20%) and 46/289 (15.9%), respectively; finally at 12 months 81/126 (64%) were in remission and 21/126 (17%) in LDA. At all-timepoints up to 12 months, bDMARDs-naïve patients demonstrated a better clinical response, independently of MTX. A significant reduction in the OGC dose was observed at 3 and 12 months in all groups. The serum positivity for both rheumatoid factors (RF) and anti-citrullinated protein antibodies (ACPA) conferred a lower risk of stopping baricitinib due to inefficacy. Fifty-eight (13%) patients discontinued baricitinib due to adverse events, including thrombotic events and herpes zoster reactivation. CONCLUSIONS: Real-life data confirm the efficacy and safety profiles of baricitinib in patients with RA and provide evidence that drug survival is higher in bDMARDs-naïve and seropositive patients.
32557255 Non-anti-TNF biologic agents are associated with slower worsening of interstitial lung dis 2021 Jan OBJECTIVES: To analyze the effect of disease-modifying antirheumatic drugs (DMARDs) on the outcome of interstitial lung disease secondary to rheumatoid arthritis (RA-ILD). PATIENTS AND METHODS: We performed a multicenter, prospective, observational study of patients with RA-ILD receiving DMARDs between 2015 and 2017. The patients were assessed using high-resolution computed tomography and pulmonary function tests at baseline and at 24 months. The radiological assessment was centralized. The main outcome measure at 24 months was changed in lung function (improvement, stabilization, worsening, or death). We recorded the 28-joint Disease Activity Score 28 (DAS28) and adverse events. A logistic regression analysis was performed to identify factors associated with worsening of ILD. RESULTS: After 24 months, lung disease was stabilized in 40 patients (57.1%), improved in 8 (11.4%), and worse in 21 (30.0%). One patient (1.4%) died. The factors associated with worsening of ILD in the multivariate analysis were treatment with abatacept, tocilizumab, or rituximab (OR, 0.102 [95%CI, 0.015-0.686]), DAS28 (OR, 1.969 [95%CI, 1.005-3.857]), and smoking (OR, 6.937 [95%CI, 1.378-4.900]). During follow-up, 30 patients (42.9%) experienced an adverse event, which was severe in 12 cases (17.1%). CONCLUSIONS: Lung function is stable and inflammatory activity well controlled in most patients with RA-ILD receiving treatment with DMARDs. Non-anti-TNF DMARDs reduce the risk of worsening of lung disease in 90% of patients. The inflammatory activity of RA and smoking, on the other hand, are associated with worsening. Key Points • We have performed prospectively evaluated lung and joint function in patients with RA-ILD receiving treatment with various DMARDs. • In our study, the lung function is stable and inflammatory activity well controlled in most patients with RA-ILD receiving treatment with DMARDs. • Neither csDMARDs nor anti-TNF agents were associated with a significant risk of worsening of lung disease, whereas non-anti-TNF bDMARDs could reduce the risk of worsening of lung disease. • Smoking and poor control of joint involvement were the main factors associated with worsening of lung disease.
34155846 Efficacy and Safety of Biosimilar and Originator Etanercept in Rheumatoid Arthritis Patien 2021 Jun BACKGROUND: There is a lack of real-life clinical data for biosimilar etanercept, an anti-TNF blocking fusion protein. We describe the comparable efficacy and safety of originator and biosimilar etanercept in rheumatoid arthritis (RA) patients in a real-life clinical setting. Our data confirm that a biosimilar etanercept can be safely used as first-line treatment as well as in patients switched from a previous originator compound. OBJECTIVES: To compare the efficacy and safety of originator and biosimilar etanercept in a cohort of RA patients attending two Italian hospitals. METHODS: The study involved 81 consecutive adult RA patients treated for at least 6 months with originator or biosimilar etanercept and considered their clinical and laboratory data, concomitant medications, and adverse events at baseline, and after 3 and 6 months of treatment. RESULTS: Group 1 included 51 patients taking originator etanercept; group 2 included 30 taking biosimilar etanercept, including 19 who had been switched from the reference product. Despite a significant baseline difference in clinical disease activity, one-way analysis of variance showed that the two groups were clinically comparable after 6 months of treatment, and the same was true when only those receiving etanercept as first-line biological treatment were considered. Nine patients discontinued the treatment due to inefficacy or adverse events, which were never serious and were only reported in group 1. CONCLUSIONS: The efficacy and safety profiles of originator and biosimilar etanercept are comparable in RA patients in a real-life clinical setting. Further studies are needed to confirm these preliminary findings.
34708132 Dissecting the Molecular Mechanism of Wang-Bi Capsule in the Treatment of Experimental Rhe 2021 Wang-Bi capsule (WB) is a traditional Chinese medicine formula and has been applied for rheumatoid arthritis (RA) treatment for many years. However, its underlying molecular mechanisms still remain unclear. In this study, collagen-induced arthritis (CIA) rats were used to observe the therapeutic effect of WB used at different time points, and the proteomic analysis of synovial tissue was applied to reveal its basic molecular mechanisms. The results demonstrated that WB not only effectively ameliorated the symptoms and synovitis, but also downregulated the serum levels of inflammatory cytokines/chemokines in CIA rats. Furthermore, the proteomic analysis of synovial tissue showed that WB could regulate several signaling pathways associated with inflammation or cell migration, such as "IL-1 signaling," "IL-8 signaling," and "CXCR4 signaling." The expression levels of proteins including matrix metalloproteinase 3 (MMP3), MMP19, lipopolysaccharide-binding protein (LBP), serine/threonine kinase interleukin-1 receptor-associated kinase 4 (IRAK4), and actin-related protein 2/3 complex subunit 5 (ARPC5) in these pathways were downregulated significantly by WB when compared with the model group. In sum, this study indicated that WB had obvious inhibitory effects on synovitis of CIA rats, and the mechanisms of which may be involved in downregulating the expression levels of several key proteins including MMP3, MMP19, LBP, IRAK4, and ARPC5.
33590850 Thymus variants on imaging in patients with rheumatoid arthritis-clinical and immunologica 2021 Dec 1 OBJECTIVES: We sought to clarify the presence of radiographic thymus variants using a scoring system, and their association with clinical and immunological features in RA patients. METHODS: A total of 387 RA patients were randomly selected from all patients visiting our department who underwent chest CT scanning, with exclusion of patients with thymoma or thymic cyst, or age < 30 years. Thymus size and attenuation score in axial CT images were quantitatively interpreted and assessed. Associations between immunophenotype data and clinical and serological features were analysed in a subset of patients. RESULTS: Thymic enlargement was found in 76 (19.6%) patients, and a thymus attenuation score ≥ 2 was found in 50 (12.9%) patients. The score was significantly associated with antibodies to ACPA positivity. Thymic enlargement was significantly associated with the proportions of CD4+ effector memory T cells. CONCLUSION: Radiographic thymus variants were frequently observed in RA patients and may reflect an abnormal immune response involved in the pathogenesis of RA.
33567493 Capsaicin-Sensitive Peptidergic Sensory Nerves Are Anti-Inflammatory Gatekeepers in the Hy 2021 Feb 8 Capsaicin-sensitive peptidergic sensory nerves play complex, mainly protective regulatory roles in the inflammatory cascade of the joints via neuropeptide mediators, but the mechanisms of the hyperacute arthritis phase has not been investigated. Therefore, we studied the involvement of these afferents in the early, "black box" period of a rheumatoid arthritis (RA) mouse model. Capsaicin-sensitive fibres were defunctionalized by pretreatment with the ultrapotent capsaicin analog resiniferatoxin and arthritis was induced by K/BxN arthritogenic serum. Disease severity was assessed by clinical scoring, reactive oxygen species (ROS) burst by chemiluminescent, vascular permeability by fluorescent in vivo imaging. Contrast-enhanced magnetic resonance imaging was used to correlate the functional and morphological changes. After sensory desensitization, both early phase ROS-burst and vascular leakage were significantly enhanced, which was later followed by the increased clinical severity scores. Furthermore, the early vascular leakage and ROS-burst were found to be good predictors of later arthritis severity. We conclude that the anti-inflammatory role of peptidergic afferents depends on their activity in the hyperacute phase, characterized by decreased cellular and vascular inflammatory components presumably via anti-inflammatory neuropeptide release. Therefore, these fibres might serve as important gatekeepers in RA.