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ID PMID Title PublicationDate abstract
34894330 Development, psychometric evaluation and cognitive debriefing of the rheumatoid arthritis 2021 Dec 11 BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease often associated with persistent pain. There is a need for a patient-reported outcome measure (PROM) that is rooted in the patient experience and psychometrically validated. We describe the development of the Rheumatoid Arthritis Symptom and Impact Questionnaire (RASIQ), a novel PROM with potential to record key symptoms and impacts of RA with a 24-h recall period. RESULTS: A literature review identified RA concepts that patients considered most important to their disease experience, including pain, fatigue, joint swelling and stiffness. From this, an initial item pool (33 items; 27 related to symptoms, 6 related to impacts) was developed with a recall period of 24 h. Two rheumatologists evaluated each item's relevance, and the second version of the RASIQ was refined (29 items; 21 related to symptoms, 8 related to impacts). Next, three rounds of cognitive debriefing interviews were conducted with patients with RA (n = 15 overall). The RASIQ was revised to remove items deemed irrelevant or redundant, leaving 16 items measuring symptoms (joint pain, energy/tiredness, joint stiffness) and impacts (rest, sleep). A parallel series of semi-structured concept elicitation interviews (n = 30) facilitated the design of a conceptual model of RA symptoms, impacts and treatment experiences. Post-hoc comparison of the model with RASIQ revealed that all items selected were among the most important and relevant symptoms and impacts for patients. A final round of cognitive debriefing interviews (n = 12) confirmed that the final 16-item RASIQ was relevant and easy to understand, with no further changes recommended. Psychometric evaluation using data from two Phase II RA clinical trials confirmed a 3-factor structure, as well as the reliability and validity of the scale scores, and the ability of RASIQ to detect changes in symptoms and impacts when administered at specific study timepoints, using a 24-h recall period. CONCLUSIONS: RASIQ is a novel, 16-item PROM developed with substantial patient input. Results from concept elicitation, cognitive debriefing, and psychometric evaluation confirmed the validity of the instrument, which has the potential to measure symptoms and impacts through a 24-h recall period and complement existing disease activity instruments with longer recall periods.
34313159 OCT retinal angiography features in patients with rheumatoid arthritis: A pilot study. 2021 Jul 27 PURPOSE: To evaluate the superficial (SCP) and deep retinal capillary plexus (DCP) by mean of optical coherence tomography angiography (OCTA) in treatment-naïve patients affected by rheumatoid arthritis (RA). METHODS: Between March 2019 and January 2020, patients with recent diagnosis of "definite RA" based on 2010 Rheumatoid Arthritis Classification Criteria were included in a Prospective, observational single center case-control study carried out at G.B. Bietti Foundation. Data were compared with those of 16 healthy age- and sex-matched subjects. Values of the vessel density (VD) of SCP and DCP, central foveal thickness (CFT), foveal avascular zone (FAZ) were collected by mean of OCTA. Main outcome measure was the VD alteration of SCP and DCP in treatment-naïve RA-patients. RESULTS: No difference in age, sex-distribution, best-corrected visual acuity, CFT was registered between the two groups. OCTA data analysis showed in RA-patients a statistically significant reduction in the VD in the mean global area, inner ring, especially in the superior quadrant of the SCP. A trend of VD reduction was also registered in temporal, nasal, and inferior quadrants, respectively, although it did not reach a statistically significant value. Assessment of VD of DCP and FAZ area did not evidence any difference among the groups. CONCLUSIONS: OCTA allows to highlight the vascular remodeling of the retinal microcirculation in RA-patients, even in early stages of the disease, demonstrating a reduction of VD. Outcomes of the current investigation can provide new insight in the pathogenetic mechanism of RA and extend the potential applications of this diagnostic tool.
33245555 Update on the Safety Profile of Tofacitinib in Rheumatoid Arthritis from Clinical Trials t 2021 Mar Tofacitinib is approved for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who do not respond adequately or are intolerant to one or more disease-modifying anti-rheumatic drugs. The tofacitinib RA clinical development program included randomized controlled trials of 6-24-month duration and long-term extension studies with > 7061 patients and 22,875 patient-years of exposure. To date, there are no data from other randomized studies in patients with cardiovascular risk factors comparing the long-term safety of a JAK inhibitor versus an anti-TNF. Real-world studies are necessary to complete the body of evidence supporting the effectiveness and safety of a therapeutic agent. In the case of tofacitinib, real-world data derive from health insurance claims databases, registries (US Corrona Registry, Swiss Registry, and others), national pharmacovigilance programs, and hospital databases (case series). The present article provides complete and up-to-date information on the safety profile of tofacitinib in RA, from clinical trials to real-world studies. Tofacitinib has demonstrated a consistent safety profile during up to 9.5 years of experience in randomized controlled trials and long-term extension studies. Real-world evidence has not added new safety issues with respect to those found in the clinical program. In general, the safety profile of tofacitinib is consistent with that of biologic disease-modifying anti-rheumatic drugs, with an increased risk of herpes zoster that seems to be a class effect of Janus kinase inhibitors. The continuous follow-up of therapeutic agents to treat rheumatoid arthritis is needed to adequately establish the safety profile for new mechanisms of action and potential risks associated with their longer term use.
34874821 Post-COVID-19 syndrome in patients with primary Sjögren's syndrome after acute SARS-CoV-2 2021 Nov OBJECTIVES: To analyse the frequency and characteristics of post-COVID-19 syndrome in patients with primary Sjögren's syndrome (pSS) affected by acute SARS-CoV-2 infection. METHODS: By the first week of April 2021, all centres included in the Big Data Sjögren Consortium were contacted asking for patients included in the Registry diagnosed with SARSCoV-2 infection according to the ECDC guidelines. According to the NICE definitions, symptoms related to COVID-19 were classified as acute COVID-19 (signs and symptoms for up to 4 weeks), ongoing symptomatic COVID-19 (presence of signs and symptoms from 4 to 12 weeks) and post-COVID-19 syndrome (signs and symptoms that continue for > 12 weeks not explained by an alternative diagnosis after a protocolized study). RESULTS: We identified 132 patients who were followed a mean follow-up of 137.8 days (ranging from 5 days to 388 days) after being diagnosed with COVID-19. In the last visit, 75 (57%) patients remained symptomatic: 68 (52%) remained symptomatic for more than 4 weeks fulfilling the NICE definition for ongoing symptomatic post-COVID-19, and 38 (29%) remained symptomatic for more than 12 weeks fulfilling the definition of post-COVID-19 syndrome. More than 40% of pSS patients reported the persistence of four symptoms or more, including anxiety/depression (59%), arthralgias (56%), sleep disorder (44%), fatigue (40%), anosmia (34%) and myalgias (32%). Age-sex adjusted multivariate analysis identified raised LDH levels (OR 10.36), raised CRP levels (OR 7.33), use of hydroxychloroquine (OR 3.51) and antiviral agents (OR 3.38), hospital admission (OR 8.29), mean length of hospital admission (OR 1.1) and requirement of supplemental oxygen (OR 6.94) as factors associated with a higher risk of developing post-COVID-19 syndrome. A sensitivity analysis including hospital admission in the adjusted model confirmed raised CRP levels (OR 8.6, 95% CI 1.33-104.44) and use of hydroxychloroquine (OR 2.52, 95% CI 1.00-6.47) as the key independent factors associated with an enhanced risk of developing post-COVID-19 syndrome. CONCLUSIONS: This is the first study that analyses the frequency and characteristics of post-COVID-19 syndrome in patients affected by a systemic autoimmune disease. We found that 57% of patients with pSS affected by COVID-19 remain symptomatic after a mean follow-up of 5 months. The risk of developing post-COVID-19 syndrome in patients who required hospitalisation was 8-times higher than in non-hospitalised patients, with baseline raised CRP levels and the use of hydroxychloroquine being independent risk factors for post-COVID-19.
34665706 Clinical determinants of vaginal dryness in patients with primary Sjögren's syndrome. 2021 Nov OBJECTIVES: The majority of women with primary Sjögren's syndrome (pSS) suffer from vaginal dryness, which negatively impacts daily and sexual activities. As little is known about the aetiology and clinical context of this complaint, this study investigated the relationship between vaginal dryness and other clinical parameters associated with pSS. METHODS: Female participants of the REgistry of Sjögren syndrome at UMCG - LongiTudinal (RESULT) cohort who fulfilled ACR-EULAR and/or AECG classification criteria for pSS were included, using baseline data for analyses. Patient-reported vaginal dryness (range 0-10) was correlated with demographic characteristics, systemic disease activity (i.e., ESSDAI), Sjögren's Syndrome Disease Damage Index, salivary and lacrimal gland function, patient-reported outcomes (ESSPRI, MFI), serology and quality of life (SF-36, EQ-5D). Significantly associated parameters (p<0.05) were corrected for potential confounders. RESULTS: This cross-sectional study included 199 women with pSS; mean age was 52±14 years, 53% were postmenopausal, and median vaginal dryness score was 5 (IQR 2-7). Vaginal dryness was significantly associated with older age, postmenopausal status, peripheral neuropathy, oral and ocular dryness, ESSPRI and SF-36 mental and general health. After correction for age, menopausal status and medication use, peripheral neuropathy (B=1.632), oral dryness (B=0.302), and ocular dryness (B=0.230) were independently associated with vaginal dryness. CONCLUSIONS: The independent association of vaginal dryness with oral and ocular dryness might imply that the aetiology of these symptoms is partly shared. Of all extraglandular features, only peripheral neuropathy was independently associated with vaginal dryness, suggesting that peripheral neuropathy plays a significant role in the pathology of vaginal dryness in pSS.
33737825 Estrogen Protects Articular Cartilage by Downregulating ASIC1a in Rheumatoid Arthritis. 2021 PURPOSE: The severity of rheumatoid arthritis (RA) in women is generally lower than that in men. RA is mediated, at least in part, by the protective effects of estradiol. However, the mechanisms underlying the protective effect of estradiol on RA are still unclear. Recent studies have demonstrated that activation of acid-sensing ion channel 1a (ASIC1a) by tissue acidosis plays an important role in the injury of cartilage in RA. Here, we assessed the effects of estradiol on acid-mediated cartilage injury both in vitro and in vivo and explored the involvement of ASIC1a in RA and its underlying mechanism. METHODS: Cultured primary articular chondrocytes were subjected to acidosis-mediated injury in vitro. Beclin1, LC3, p62, GPER1, and ASIC1a expression was detected through Western blotting, quantitative real-time PCR, and immunofluorescence analysis. Adjuvant arthritis (AA) was induced in rats through intradermal immunization by injecting 0.25 mL heat-killed mycobacteria (10 mg/mL) suspended in complete Freund's adjuvant into the left hind metatarsal footpad. The levels of estrogen and related inflammatory factors in the serum were measured using enzyme-linked immunosorbent assay. The expression of ASIC1a and autophagy-related proteins was detected through immunohistochemical analysis and Western blot. RESULTS: Treatment of primary articular chondrocytes with estradiol decreased the expression of ASIC1a and autophagy level. The symptoms of cartilage damage and levels of inflammatory cytokines in the serum were reduced after estradiol treatment in the rats with AA. In addition, estradiol treatment reduced ASIC1a expression via the PI3K-AKT-mTOR pathway, among which G-protein coupled estradiol receptor 1 (GPER1) plays a regulatory role. Finally, the level of autophagy in chondrocytes was decreased by the selective ASIC1a blocker psalmotoxin-1 (PCTX-1). CONCLUSION: Estradiol can protect the cartilage of rats with AA against acidosis-mediated damage and autophagy by suppressing ASIC1a expression through GPER1.
33834034 Bone Erosions Detected by Ultrasound Are Prognostic for Clinical Arthritis Development in 2021 Anti-citrullinated protein antibodies (ACPA) often precede onset of rheumatoid arthritis (RA) by years, and there is an urgent clinical need for predictors of arthritis development among such at-risk patients. This study assesses the prognostic value of ultrasound for arthritis development among ACPA-positive patients with musculoskeletal pain. We prospectively followed 82 ACPA-positive patients without clinical signs of arthritis at baseline. Ultrasound at baseline assessed synovial hypertrophy, inflammatory activity by power Doppler, and erosions in small joints of hands and feet. We applied Cox regression analyses to examine associations with clinical arthritis development during follow-up (median, 69 months; range, 24-90 months). We also compared the ultrasound findings among the patients to a control group of 100 blood donors without musculoskeletal pain. Clinical arthritis developed in 39/82 patients (48%) after a median of 6 months (range, 1-71 months). One or more ultrasound erosions occurred in 13/82 patients (16%), with none in control subjects (p < 0.001). Clinical arthritis development was more common among patients with baseline ultrasound erosions than those without (77 vs. 42%, p = 0.032), and remained significant in a multivariable Cox regression analysis that included previously described prognostic factors (HR 3.9, 95% CI 1.6-9.4, p = 0.003). Ultrasound-detected tenosynovitis was more frequent among the patients and associated with clinical arthritis development in a univariable analysis (HR 2.5, 95% CI 1.1-5.7, p = 0.031), but did not remain statistically significant in multivariable analysis. Thus, bone erosions detected by ultrasound are independent predictors of clinical arthritis development in an ACPA-positive at-risk population. Trial Registration: Regional Ethics Committee in Linköping, Sweden, Dnr M220-09. Registered 16 December 2009, https://etikprovningsmyndigheten.se/.
34712532 Association Between Rheumatoid Arthritis and Serum Vitamin D Levels. 2021 Sep Introduction Vitamin D is responsible for regulating innate and adaptive immune responses and for boosting the immune system; hence, a decline in its levels results in autoimmunity. Current studies have linked the deficiency of vitamin D to different autoimmune diseases, including rheumatoid arthritis (RA). In this study, we will determine the association between vitamin D level and RA. Methods This is a case-control study, conducted in a tertiary care hospital in Pakistan from January 2021 to May 2021. Three hundred patients with a confirmed recent diagnosis of RA were enrolled as the study group. Another 300 participants without RA, matched for age and gender, were enrolled in the study as a control group. RA was diagnosed on the basis of clinical symptoms, radiological features on X-ray, and anti-citrullinated protein levels of more than 20 u/mL. Results The mean vitamin D level in participants with RA was significantly lower than in the placebo group (30.18 ± 6.27 vs. 38.29 ± 7.98; p-value: <0.0001). The mean vitamin D level in participants with positive RF patients was significantly lower compared to rheumatoid factor (RF)-negative RA patients (29.21 ± 5.16 vs. 32.26 ± 7.02; p-value: <0.0001). There were more participants with hypovitaminosis D in RF-positive participants as compared to RF negative (88.6% vs. 44.3%; p-value: 0.00001). Conclusion There is a high prevalence of vitamin D deficiency in patients with RA and there is a link with disease severity. Therefore, a high index of suspicion is required while evaluating the at-risk patients, especially women, with complaints of vitamin D deficiency. Vitamin D supplementation may be needed for the prevention or avoidance of the progression of the disease.
34962619 Comparison of Clinical Manifestations in Rheumatoid Arthritis vs. Spondyloarthritis: A Sys 2022 Apr INTRODUCTION: Misclassification of spondyloarthritis (SpA) as rheumatoid arthritis (RA) may lead to delayed SpA diagnosis and suboptimal therapeutic outcomes. Here, we evaluate the literature on clinical manifestations in patients with SpA and RA, particularly seronegative RA, to understand the potential overlap, distinctions, and most reliable approaches to accurate diagnosis. METHODS: In this systematic literature review, conducted according to PRISMA guidelines, we searched key biomedical databases for English-language publications of original research articles (up to July 23, 2020) and rheumatology conference abstracts (January 1, 2018-July 31, 2020) reporting key SpA clinical presentations in patients with SpA or RA. Publications were assessed for eligibility by two independent reviewers; discrepancies were resolved by a third. Studies were evaluated for publication quality using the Downs and Black checklist. RESULTS: Of 4712 records retrieved, 79 met the inclusion criteria and were included in the analysis. Of these, 54 included study populations with SpA and RA, and 25 with seropositive and/or seronegative RA. Entheseal abnormalities were more frequently reported among patients with SpA than RA and with seronegative vs. seropositive RA. Psoriasis, nail psoriasis, and dactylitis were exclusively seen in SpA vs. RA. In most publications (70 of 79), advanced imaging techniques allowed for more accurate distinction between SpA and RA. Overlapping clinical characteristics occur in SpA and RA, including inflammation and destruction of joints, pain, diminished functional ability, and increased risk for comorbidities. However, of 54 studies comparing SpA and RA populations, only seven concluded that no distinction can be made based on the SpA manifestations and outcomes examined. CONCLUSIONS: Typical SpA-related clinical symptoms and signs were observed in patients with RA, suggesting that misclassification could occur. Availability of advanced imaging modalities may allow for more prompt and comprehensive evaluation of peripheral manifestations in SpA and RA, reducing misclassification and delayed diagnosis.
35423998 Hyaluronic acid-green tea catechin conjugates as a potential therapeutic agent for rheumat 2021 Apr 15 Fibroblast-like synoviocytes are a key effector cell type involved in the pathogenesis of rheumatoid arthritis. The major green tea catechin, epigallocatechin-3-O-gallate (EGCG), has attracted significant interest for rheumatoid arthritis therapy because of its ability to suppress the proliferation and interleukin-6 secretion of synoviocytes. However, therapeutic efficacy of EGCG has been limited by a lack of target cell specificity. Herein we report hyaluronic acid-EGCG (HA-EGCG) conjugates as an anti-arthritic agent that is capable of targeting fibroblast-like synoviocytes via HA-CD44 interactions. These conjugates exhibited superior anti-proliferative and anti-inflammatory activities compared with EGCG under simulated physiological conditions. Near-infrared fluorescence imaging revealed preferential accumulation of the conjugates at inflamed joints in a collagen-induced arthritis rat model, and their anti-arthritic efficacy was investigated by measuring a change in the edema and histopathological scores. Our findings suggest the potential of HA-EGCG conjugates as an anti-arthritic agent for the treatment of rheumatoid arthritis.
35005250 Osteosarcopenia synergistically increases the risk of falls in patients with rheumatoid ar 2021 Dec OBJECTIVES: Osteosarcopenia is defined as osteoporosis with sarcopenia. The impacts of osteosarcopenia on falls and fractures in rheumatoid arthritis (RA) patients were investigated using 4 years of data from a longitudinal study (CHIKARA study). METHODS: The patients were divided into 4 groups by their baseline status: no sarcopenia and no osteoporosis (SP-OP-); only sarcopenia (SP + OP-); only osteoporosis (SP-OP+); and both sarcopenia and osteoporosis (SP + OP+). Survival rates and Cox hazard ratios were analyzed using falls and fractures as endpoints, adjusted by age, sex, and body mass index. RESULTS: A total of 100 RA patients (SP-OP-: 44%, SP + OP-: 17%, SP-OP+: 28%, and SP + OP+: 11%) were enrolled; 37 patients had falls, and 19 patients had fractures. The fall-free and fracture-free survival rates were significantly lower in SP + OP+ (36.4%, 54.5%) than in SP-OP- (75.0%, 86.4%). The hazard ratio of falls was significantly increased in SP + OP+, by 3.32-fold (95%CI: 1.01-10.9), whereas in SP + OP- and SP-OP+, there were no differences compared to SP-OP-. CONCLUSIONS: The survival rates with the endpoints of falls and fractures in RA patients with osteosarcopenia were lower during 4-year follow-up. The risk of falls increased with the synergistic effect of osteoporosis and sarcopenia.
35056507 Another Look at the Contribution of Oral Microbiota to the Pathogenesis of Rheumatoid Arth 2021 Dec 28 Although autoimmunity contributes to rheumatoid arthritis (RA), several lines of evidence challenge the dogma that it is mainly an autoimmune disorder. As RA-associated human leukocyte antigens shape microbiomes and increase the risk of dysbiosis in mucosae, RA might rather be induced by epigenetic changes in long-lived synovial presenting cells, stressed by excessive translocations into joints of bacteria from the poorly cultivable gut, lung, or oral microbiota (in the same way as more pathogenic bacteria can lead to "reactive arthritis"). This narrative review (i) lists evidence supporting this scenario, including the identification of DNA from oral and gut microbiota in the RA synovium (but in also healthy synovia), and the possibility of translocation through blood, from mucosae to joints, of microbiota, either directly from the oral cavity or from the gut, following an increase of gut permeability worsened by migration within the gut of oral bacteria such as Porphyromonas gingivalis; (ii) suggests other methodologies for future works other than cross-sectional studies of periodontal microbiota in cohorts of patients with RA versus controls, namely, longitudinal studies of oral, gut, blood, and synovial microbiota combined with transcriptomic analyses of immune cells in individual patients at risk of RA, and in overt RA, before, during, and following flares of RA.
34851442 [Polymyalgia rheumatica in 18-fluorodeoxyglucose-positron-emission-tomography/computed tom 2021 Dec 1 BACKGROUND: The diagnosis of patients with polymyalgia rheumatica (PMR) has relied upon the clinical examination of symptoms and laboratory parameters of inflammation until now. Currently, the use of different imaging modalities is being explored, including ultrasound, MRI and PET. OBJECTIVES: The aim was to evaluate the diagnostic value of 18-fluorodeoxyglucose-positron-emission-tomography/computed tomography (18F-FDG-PET/CT) for PMR, in order to improve the sensitivity and specificity of diagnosing PMR and to improve the differential diagnosis of rheumatoid arthritis (RA). MATERIALS AND METHODS: Examinations using 18F-FDG-PET/CT of 284 rheumatological patients, including 97 patients with PMR, were retrospectively evaluated over a 44-month period. Furthermore, 13 regions changed by inflammation were analysed via a three-dimensional region of interest (ROI) measurement with determination of maximum standardized uptake values (SUVmax), followed by statistical analyses. RESULTS AND DISCUSSION: Patients with PMR presented significantly elevated uptake in all regions examined (p < 0.001), compared with a control group treated for rheumatological diseases. The method with the highest diagnostic relevance was represented by the combination of four SUVmax values of both anterolateral hip capsules and both ischial tuberosities, reaching a sensitivity of 91.3% and a specificity of 97.6% with a cut-off of 11.0 SUV at the initial diagnosis of PMR patients who had not yet received any immunosuppressive therapy. Patients with RA could be significantly distinguished from those with PMR at initial diagnosis in the same anatomical regions (p < 0.001).
34850088 MicroRNA-106b Overexpression Suppresses Synovial Inflammation and Alleviates Synovial Dama 2021 Nov 27 OBJECTIVES: To explore the effect of miR-106b on synovial inflammation and damage in rheumatoid arthritis (RA) patients, and further to investigate its possible mechanism. METHODS: : Quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence, in situ hybridization and immunohistochemistry assay were separately used to verify the levels of miR-106b and cytokines in the synovial tissues of patients with RA or osteoarthritis (OA). Pearson correlation analysis was conducted to examine the bivariate relationship between miR-106b and cytokines or RANKL. Following the isolation and culture of fibroblast-like synoviocytes (FLS), the cells were transfected with lentivirus-mediated miR-106b mimic, miR-106b inhibitor, and negative control miR-106b mimic, respectively. Thereafter, cell proliferation was measured by Cell Counting Kit-8 assay, and cell invasion and migration capacity was assessed by Transwell assay. Furthermore, concentration and expression of cytokines were separately detected by Enzyme linked immunosorbent assay and Western blot. RESULTS: Compared with osteoarthritis, validation by qRT-PCR showed that RA patients had a lower level of miR-106b and higher levels of receptor activator of nuclear factor-κ B ligand (RANKL), tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6). Additionally, the scatter plot showed that the relative transcription of miR-106b level was negatively correlated to the level of TNF-a, IL-6, and RNKAL in the synovial tissues of both RA and OA patients (All P<0.05). Furthermore, miR-106b overexpression suppressed cell proliferation, migration and invasion capacity of human RA-FLS. CONCLUSIONS: miR-106b overexpression suppresses synovial inflammation and alleviates synovial damage, thus it may be served as a potential therapeutic target for RA patients.
34228181 Comparative efficacy and safety of infliximab and its biosimilars in patients with rheumat 2021 Jul 6 OBJECTIVE: To assess the relative efficacy and safety of infliximab and its biosimilars in patients with active rheumatoid arthritis (RA) who showed an inadequate response to methotrexate (MTX). METHODS: We performed a Bayesian network meta-analysis combining direct and indirect evidence from randomized controlled trials (RCTs), comparing the efficacy and safety of infliximab biosimilars versus the originator product in patients with active RA despite receiving MTX. RESULTS: Overall, 7 RCTs involving 3168 patients, including 7 biologic agents, met the inclusion criteria. The NI-071 was listed at the top left of the diagonal of the league table because it was associated with the most favorable surface under the cumulative ranking curve (SUCRA) for the American College of Rheumatology 20 (ACR20) response rate. SB2 was listed at the bottom right of the diagonal of the league table because it was associated with the least favorable results. Based on SUCRA, NI-071 had the highest probability of being the best treatment agent in terms of the ACR20 response rate (SUCRA = 0.731), followed by ABP 710, CT-P13, BCD-055, infliximab, Exemptia, PF-06438179, and SB2 (SUCRA = 0.311). Although statistically non-significant differences in safety ranking were observed for serious adverse events (SAEs) among the treatment options, ABP 710 presented the highest safety probability (SUCRA = 0.739) while BCD-055 showed the lowest safety profile (SUCRA = 0.289). CONCLUSION: No significant difference in ACR20 response rates and SAEs were detected between infliximab biosimilars and the originator in the investigated study populations.
33999266 Comparative efficacy and safety of adalimumab biosimilars and adalimumab in patients with 2021 May 17 OBJECTIVE: We assessed the relative efficacy and safety of adalimumab and biosimilars in patients with active rheumatoid arthritis (RA) presenting an inadequate response to methotrexate (MTX). METHODS: We performed a Bayesian network meta-analysis combining direct and indirect evidence from randomized controlled trials (RCTs) examining efficacy and safety of adalimumab biosimilars versus adalimumab in patients with active RA despite MTX therapy. RESULTS: Overall, 8 RCTs involving 3577 patients, including 8 biologic types, met the inclusion criteria. MSB11022 is listed at the top left of the diagonal of the league table, as it was associated with the most favorable surface under the cumulative ranking curve (SUCRA) for the American College of Rheumatology 20 (ACR20) response rate; FKB327 is listed at the bottom right of the diagonal of the league table, as it was associated with the least favorable results. Based on SUCRA, MSB11022 presented the highest probability of being the best treatment for achieving the ACR20 response rate (SUCRA = 0.623), followed by PF-06410293, CinnoRA, BI 695501, ABP 50, Exemptia, SB5, adalimumab, and FKB327 (SUCRA = 0.390); no difference was observed in ACR20 response rates between biosimilars and adalimumab. Although statistically non-significant, differences in safety ranking were observed for serious adverse events (SAEs) among the interventions, with MSB11022 presenting the highest probability of being safe (SUCRA = 0.865) and Exemptia the lowest (SUCRA = 0.300). CONCLUSION: No significant difference was detected between adalimumab biosimilars and the originator in terms of ACR20 response rates and SAEs in the studied patients.
35095899 Cytohesin-2/ARNO: A Novel Bridge Between Cell Migration and Immunoregulation in Synovial F 2021 The guanine nucleotide exchange factor cytohesin-2 (ARNO) is a major activator of the small GTPase ARF6 that has been shown to play an important role(s) in cell adhesion, migration and cytoskeleton reorganization in various cell types and models of disease. Interestingly, dysregulated cell migration, in tandem with hyper-inflammatory responses, is one of the hallmarks associated with activated synovial fibroblasts (SFs) during chronic inflammatory joint diseases, like rheumatoid arthritis. The role of ARNO in this process has previously been unexplored but we hypothesized that the pro-inflammatory milieu of inflamed joints locally induces activation of ARNO-mediated pathways in SFs, promoting an invasive cell phenotype that ultimately leads to bone and cartilage damage. Thus, we used small interference RNA to investigate the impact of ARNO on the pathological migration and inflammatory responses of murine SFs, revealing a fully functional ARNO-ARF6 pathway which can be rapidly activated by IL-1β. Such signalling promotes cell migration and formation of focal adhesions. Unexpectedly, ARNO was also shown to modulate SF-inflammatory responses, dictating their precise cytokine and chemokine expression profile. Our results uncover a novel role for ARNO in SF-dependent inflammation, that potentially links pathogenic migration with initiation of local joint inflammation, offering new approaches for targeting the fibroblast compartment in chronic arthritis and joint disease.
35079182 Ultrasound remission in patients with rheumatoid arthritis in clinical remission. 2021 OBJECTIVES: The aim of the study was to assess ultrasound (US) remission in patients with rheumatoid arthritis (RA) in clinical remission using different definitions. MATERIAL AND METHODS: This was a cross-sectional study including patients with RA in clinical remission defined by disease activity score (DAS28)-erythrocyte rate (ESR) ≤ 2.6 for at least 6 months. Each patient underwent B-mode and power Doppler (PD) assessments of 42 joints and 20 tendons. B-mode and PD signal for synovitis and tenosynovitis (TS) were defined and graded semi-quantitatively (0-3) according to the outcome measures in rheumatology clinical trials (OMERACT). Several different definitions of US remission were examined: the absence of synovial hypertrophy (SH), TS on B-mode and PD signal, the absence of SH and PD signal, a grade ≤ 1 of SH and the absence of PD, a grade ≤ 1 of SH and PD, the absence of PD, or a grade of PD ≤ 1. The DAS28, clinical disease activity index (CDAI), simple disease activity index (SDAI), and the Boolean American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission criteria were compared. RESULTS: Thirty-seven patients were enrolled. The rate of remission according to the different composite indices was 70.2% for the SDAI, 64.8% for the CDAI, and 54% for the ACR/EULAR Boolean criteria. Synovial hypertrophy and TS in B-mode were detected in 94.6% and 40.5% of patients, respectively. Synovitis with PD signal was found in 59.5% and 13.5% of patients had TS with PD, respectively. Ultrasound remission at joints and tendons was found in 5.4-62.2% of patients. For the other remission criteria: CDAI, SDAI, and ACR/EULAR Boolean criteria, 7.7-60% of patients showed US remission at joints and tendons. CONCLUSIONS: Clinical remission, even classified by strict composite indices, does not seem to be the closest method to the concept of absence of inflammatory activity; hence the interest of integrating US in assessing remission in practice.
34908689 Assessment of Depression, Anxiety, Stress, and quality of life in rheumatoid arthritis pat 2021 Oct BACKGROUND: Rheumatoid arthritis (RA) is a disabling condition that results in considerable suffering and negatively impacts an individual's psychological, financial, social, and quality of life (QoL). Pain, fatigue, and disabilities, which may be considered as stress factors, are common challenges that may subsequently lead to psychological distress. AIM: Assessment of Depression, Anxiety, Stress, and QoL in RA patients and Comparison with healthy individuals. MATERIALS AND METHODS: This cross-sectional analytical study included 50 RA patients who have reported to a tertiary health care center on outpatient basis and an equal number of age- and sex-matched healthy individuals. The study was conducted after obtaining Institutional Ethics Committee approval and informed consent of the participants. Patients were assessed based on Disease Activity Score incorporating erythrocyte sedimentation rates, Depression Anxiety Stress Scale (DAS21), Health Assessment questionnaire, Visual Analog Scale, and Multidimensional scale of Perceived Social Support. RESULTS: Levels of anxiety, depression, and stress in patients with RA were significantly higher as compared to age- and sex-matched healthy controls. RA patients had significantly lower scores on total social support, as well as social support of family and friends. However, there was no difference between RA patients and healthy controls on social support from significant others. CONCLUSION: Patients with RA had significantly higher levels of anxiety, depression, and stress and significantly lower levels of social support compared to age- and sex-matched healthy controls. The therapeutic implications of these findings need further evaluation.
34728991 Surgical treatment outcome on a national cohort of 176 patients with cervical manifestatio 2021 Jul PURPOSE: Rheumatoid arthritis (RA) affecting the cervical spine results in instability and deformity that can be divided into the subtypes C1-C2 horizontal (atlantoaxial instability), C0-C2 vertical (basilar invagination), subaxial, and combined instabilities. The aim of this study was to compare the surgical treatments and outcomes of RA-related deformity and instability in a population-based setting. PATIENTS AND METHODS: All patients with RA in the national Swespine register from January 1, 2006, to March 20, 2019, were assessed. Baseline characteristics, surgical treatments, European Myelopathy Scale (EMS), Neck Disability Index, the Visual Analog Scale for neck and arm pain as well as pre- and postoperative imaging were analyzed. The follow-up time points were at 1-, 2-, and 5 years after surgery. RESULTS: A total of 176 patients were included. There were 62 (35%) patients with C1-C2 horizontal instability, 48 (27%) with C0-C2 vertical instability, 19 (11%) patients with subaxial instability, 43 (24%) patients with combined instability, and 4 patients without instability served as controls. The EMS improved in the C1-C2 horizontal instability group after fusion surgery (Δ =2.6 p) but remained within baseline confidence intervals in the other groups. All patients regardless of instability improved in pain. The subaxial instability had the highest risk of death within 5 years after surgery (11/19, 58%). The most dangerous complications due to implant failure were seen in patients instrumented with laminar hooks. CONCLUSION: The neurological outcome after fusion surgery is poor and the death rate is high in patients with cervical RA-related instability and deformity.