Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
32944882 Bidirectional association between GERD and rheumatoid arthritis: two longitudinal follow-u 2021 Apr Several previous studies have suggested a relationship between GERD and RA. However, no study has investigated the bidirectional relationship between GERD and RA. This study aimed to evaluate the causal relationships between rheumatoid arthritis (RA) and gastroesophageal reflux disease (GERD). Participants aged ≥ 20 years old in the Korean Health Insurance Review and Assessment Service-National Sample Cohort from 2002 to 2013 were enrolled. In study I, 132,140 GERD participants were 1:2 matched with 264,280 control I participants. In study II, 6615 RA participants were 1:4 matched with 26,460 control II participants. Both control I and control II groups were matched with their study groups for age, sex, income, and region of residence. The occurrence of RA (study I) and GERD (study II) were followed up in both the study and control groups. The hazard ratios (HRs) of GERD for RA (study I) and of RA for GERD (study II) were analysed using stratified Cox-proportional hazards models. In study I, 0.8% (1,034/132,140) of the GERD group and 0.5% (1,290/264,280) of the control I group had RA (P < 0.001). The GERD group demonstrated a 1.49-fold higher adjusted HR than did the control I group (95% confidence interval (95% CI) = 1.37-1.62, P < 0.001). In study II, 22.5% (1,490/6,615) of the RA group and 15.2% (4,034/26,460) of the control II group had GERD (P < 0.001). The RA group showed a 1.46-fold higher adjusted HR than did the control II group (95% CI = 1.38-1.55, P < 0.001). GERD and RA have bidirectional associations in Korean adult population. Key Points • Several previous studies have suggested a relationship between gastroesophageal reflux disease (GERD) and rheumatoid arthritis (RA). • However, no study has investigated the bidirectional relationship between GERD and RA. • This is the first study to present a bidirectional relationship between GERD and RA. • GERD and RA have bidirectional relations with each other.
33877648 Disease-Modifying Antirheumatic Drugs (DMARDs) and drug interactions in dentistry. 2021 Apr OBJECTIVE: Rheumatoid arthritis is a chronic autoimmune disease. Treatment aims to reduce and improve its signs and symptoms. Hence, Disease-Modifying Antirheumatic Drugs (DMARDs) are the treatment of choice. The objective of this study was to identify potential interactions between DMARDs and the drugs most frequently prescribed in dentistry in order to avoid adverse reactions. MATERIALS AND METHODS: This literature review sets out to define possible adverse reactions provoked by pharmacological interactions between DMARDs and the drugs commonly prescribed in dentistry. A search was conducted in PubMed by searching the names of drugs used in dentistry, "drug interactions," "rheumatoid arthritis," and "dentistry", "hydroxychloroquine", "leflunomide", "methotrexate", "sulfasalazine", "adalimumab", "anakinra", "etanercept", "abatacept", "infliximab" and "rituximab". RESULTS: It was found that most DMARDs show potential interactions with many drugs used in dentistry, including various antibiotics, analgesics, anesthetics, antifungals, and corticosteroids. CONCLUSIONS: It is clinically important for oral health clinicians to be aware of possible drug interactions between DMARDs and the drugs commonly prescribed in dentistry to prevent potential adverse reactions and avoid endangering the patient.
33432861 Social stressors and risk of rheumatoid arthritis and their relationship to known modifiab 2021 May Objectives: To investigate whether low social support or low decision latitude at work correlate with risk of rheumatoid arthritis (RA), and whether and how those factors are associated with known modifiable risk factors for RA.Method: The Swedish population-based EIRA study included, from 1996 to 2015, 3724 incident RA cases and 5935 controls, matched for age, gender, and residential area. Participants filled in detailed questionnaires at diagnosis. Using logistic regression, we investigated whether low social support and low decision latitude at work were associated with RA risk, and whether and how these exposures are associated with known modifiable risk factors for RA.Results: Low decision latitude at work was associated with RA risk in unadjusted analyses [odd ratio (OR) = 1.52, 95% confidence interval (CI) = 1.20-1.94], but this association was weakened after adjustment for known RA risk factors (adjusted OR = 1.24, 95% CI = 0.93-1.63). Low social support was not associated with RA risk (unadjusted OR = 1.05, 95% CI = 0.95-1.15). Cases reporting low decision latitude were more often smokers (OR = 2.05, 95% CI = 1.33-3.16), without university degrees (OR = 8.23, 95% CI = 5.13-13.22), and more often female (OR = 2.52, 95% CI = 1.66-3.81), with a similar pattern among controls. Cases reporting low social support were more often men (OR = 1.60, 95% CI = 1.40-1.83), smokers (OR = 1.46, 95% CI = 1.26-1.70), obese (OR = 1.29, 95% CI = 1.09-1.54), physically inactive (OR = 2.78, 95% CI = 1.98-3.90), and without university degrees (OR = 2.04, 95% CI = 1.77-2.36), with a similar pattern among controls.Conclusion: Low decision latitude coexisted with several known environmental/social risk factors for RA, together defining groups of individuals at increased risk of RA. These risk factors should be viewed in context when testing actions to diminish RA risk in prospective studies.
34209676 Alcohol Consumption and Risk of Rheumatoid Arthritis among Chinese Adults: A Prospective S 2021 Jun 29 Alcohol consumption may be associated with the risk of rheumatoid arthritis (RA), but potential sex-related differences in this association have not been explored. Thus, we utilized 87,118 participants in the Kailuan Study, a prospective cohort initiated in 2006 to study the risk factors of cardiovascular disease in a Chinese population. We included those that did not have RA at baseline (2006), and performed cox proportional hazard modeling to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) of RA according to the levels of alcohol consumption (never or past, light or moderate (<1 serving/day for women, <2 servings/day for men), and heavy (>1 serving/day for women, >2 servings/day for men), adjusting for age, sex, body mass index, and smoking. Diagnoses of RA were confirmed via medical record review by rheumatologists. From 2006 to 2018, we identified 87 incident RA cases. After adjusting for potential confounders, the HR of RA was 1.26 (95% CI: 0.62, 2.56) for participants with light or moderate alcohol consumption and 1.98 (95% CI: 0.93, 4.22) for participants with heavy alcohol consumption) versus non-drinkers. The HR of each 10 g increase in alcohol consumption was 1.11 (95% CI: 0.98, 1.26) (p-trend = 0.09). A significant association between alcohol consumption and RA risk was observed in women, but not in men (p for interaction = 0.06). Among women, each 10 g increase in alcohol consumption was significantly associated with a high risk of RA (HR: 1.56; 95% CI: 1.06, 2.29). In contrast, each 10 g increase in alcohol consumption was not significantly associated with the risk of RA in men (HR: 1.10; 95% CI: 0.97, 1.25). Excluding past drinkers generated similar results. In this prospective Chinese cohort, increasing alcohol consumption was associated with an elevated risk of RA among women, but not in men. These findings highlight the importance of incorporating analysis of sex differences into future studies of alcohol consumption and RA risk.
33900118 Topical delivery of curcumin-loaded transfersomes gel ameliorated rheumatoid arthritis by 2021 Apr Aim: To fabricate and evaluate curcumin-loaded transfersomes (Cur-TF) for the targeted delivery and enhanced therapeutic efficacy of curcumin for the treatment of rheumatoid arthritis (RA). Methods: Modified thin-film hydration method was used to prepare Cur-TF which were then embedded into carbopol-934 gel. They were further evaluated through in vitro techniques and in an in vivo arthritis model. Results: Cur-TF had optimal particle size, spherical morphology, high encapsulation efficiency and sustained drug release profiles. The Cur-TF gel had better in vitro skin penetration than plain curcumin. In vivo findings demonstrated improved clinical, histological and x-ray scores and reduced pro-inflammatory cytokines through NF-κβ inhibition. Conclusion: Cur-TF gel delivered curcumin to the arthritic dermal tissue through a topical route and demonstrated promising therapeutic efficacy by significantly alleviating complete Freud's adjuvant (CFA)-induced arthritis.
34876670 Acute exacerbation of interstitial lung disease associated with rheumatic disease. 2022 Feb Interstitial lung disease (ILD) is a cause of morbidity and mortality in patients with rheumatic diseases, such as connective-tissue diseases, rheumatoid arthritis and systemic vasculitis. Some patients with ILD secondary to rheumatic disease (RD-ILD) experience acute exacerbations, with sudden ILD progression and high mortality during or immediately after the exacerbation, and a very low 1-year survival rate. In the ILD subtype idiopathic pulmonary fibrosis (IPF), an acute exacerbation is defined as acute worsening or development of dyspnoea associated with new bilateral ground-glass opacities and/or consolidations at high-resolution CT, superimposed on a background pattern consistent with fibrosing ILD. However, acute exacerbation in RD-ILD (AE-RD-ILD) currently has no specific definition. The aetiology and pathogenesis of AE-RD-ILD remain unclear, but distinct triggers might include infection, mechanical stress, microaspiration and DMARD treatment. At this time, no effective evidence-based therapeutic strategies for AE-RD-ILD are available. In clinical practice, AE-RD-ILD is often empirically treated with high-dose systemic steroids and antibiotics, with or without immunosuppressive drugs. In this Review, we summarize the clinical features, diagnosis, management and prognosis of AE-RD-ILD, enabling the similarities and differences with acute exacerbation in IPF to be critically assessed.
34134455 Role of Fibroblast Activation Protein Alpha in Fibroblast-like Synoviocytes of Rheumatoid 2021 Jun 6 Fibroblast-like synoviocytes (FLSs) have been introduced in recent years as a key player in the pathogenesis of rheumatoid arthritis (RA), but the exact mechanisms of their transformation and intracellular pathways have not yet been determined. This study aimed to investigate the role of fibroblast activation protein-alpha (FAP-α) in the regulation of genes involved in the transformation and pathogenic activity of RA FLSs. Synovial FLSs were isolated from RA patients and non-arthritic individuals (n=10 in both groups) and characterized; using immunocytochemistry and flow cytometry analysis. FLSs were divided into un-treated and Talabostat-treated groups to evaluate the FAP-α effect on the selected genes involved in cell cycle regulation (p21, p53, CCND1), apoptosis (Bcl-2, PUMA), and inflammatory and destructive behavior of FLSs (IL-6, TGF-β1, MMP-2, MMP-9, P2RX7). Gene expression analysis was performed by quantitative real-time polymerase chain reaction (qRT-PCR), and immunoblotting was carried out to evaluate FAP-α protein levels. The basal level of FAP-α protein in RA patients was significantly higher than non-arthritic control individuals. However, no differences were observed between RA and non-arthritic FLSs, at the baseline mRNA levels of all the genes. Talabostat treatment significantly reduced FAP-α protein levels in both RA and non-arthritic FLSs, however, had no effect on mRNA expressions except an upregulated TGF-β1 expression in non-arthritic FLSs. A significantly higher protein level of FAP-α in FLSs of RA patients compared with that of healthy individuals may point to the pathogenic role of this protein in RA FLSs. However, more investigations are necessary to address the mechanisms mediating the FAP-α pathogenic role in RA FLSs.
33185165 Safety and Efficacy of Mavrilimumab For Rheumatoid Arthritis: A Systematic Review and Meta 2021 BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by progressive swelling and stiffness in the joints. Mavrilimumab is a human monoclonal antibody that may block the autoimmune mechanism of the antibodies causing RA. OBJECTIVE: We aim to assess the safety and efficacy of Mavrilimumab in treating rheumatoid arthritis. METHODS: We conducted an online search using PubMed, Scopus, Web of Science, and Cochrane CENTRAL till June 2019, and updated the search in May 2020, using relevant keywords. We screened studies for eligibility. Data were extracted from eligible studies and pooled as Risk ratio (RR) with a 95% confidence interval (CI), using Review Manager software (ver.3.5). RESULTS: Five studies (with 1145 patients) were eligible to our criteria. Pooled result from three trials showed a significant reduction in Disease Activity Score 28 based on C-reactive protein (DAS28-CRP) remission < 2.6 after 12 weeks (RR = 3.31, 95% CI [1.53, 7.18], P = 0.002), American College of Rheumatology (ACR) 20, after 12 weeks (RR = 2.38, 95% CI [1.80, 3.16], P < 0.00001), ACR 50, after 12 weeks (RR = 2.93, 95% CI [1.67, 5.15], P = 0.0002), ACR 70, after 12 weeks (RR = 4.90, 95% CI [1.60, 15.00], P = 0.005). Mavrilimumab not associated with a significant adverse event (RR = 1.22, 95% CI [0.89, 1.68], P = 0.22). CONCLUSION: We found that subcutaneous Mavrilimumab was effective and well-tolerating in treating RA patients, with no significant adverse events.
30874488 Atlantoaxial instability in a patient with neck pain and rheumatoid arthritis. 2021 May Context: The purpose of this report is to describe the clinical decision-making process for a patient with rheumatoid arthritis with neck pain with underlying atlantoaxial instability.Findings: The patient was evaluated for worsening upper neck pain that began insidiously 1 year prior. The patient denied numbness or tingling in her upper or lower extremities, dizziness or lightheadedness, difficulty maintaining balance with walking, or muscle weakness. Cervical spine range of motion was limited in all planes due to pain and apprehension. The patient's neurological examination was unremarkable. Prior flexion and extension radiographs of the cervical spine were interpreted as unremarkable with alignment preserved in flexion and extension. However, upon further inspection, the cervical spine flexion radiograph was concerning for inadequate cervical motion, which may have limited the diagnostic utility of these radiographs. Additionally, a Sharp-Purser test was performed, which was positive for excessive motion. Flexion and extension radiographs of the cervical spine were then repeated ensuring the patient adequately flexed and extended during the imaging. Severe anterior subluxation of C1 relative to C2 with cervical flexion was noted, as C1 moved as much as 8-9 mm anterior to C2 with cervical flexion. Given the degree of atlantoaxial instability, the patient subsequently underwent successful posterior fusion from the occiput to C2.Conclusion/Clinical Relevance: This case report demonstrates the importance of properly screening for upper cervical spine instability in patients with rheumatoid arthritis and neck pain and understanding the importance of obtaining adequate and appropriate diagnostic imaging.
33916688 Vitamin D and VDR Gene Polymorphisms' Association with Rheumatoid Arthritis in Lithuanian 2021 Apr 3 Background and Objectives: Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune, multi-factorial disease, in which environmental and genetic factors play a major role. RA is possibly linked to vitamin D deficiency and vitamin D receptor (VDR) gene polymorphisms, and research demonstrates that FokI variant susceptibility is associated with increased disease risk among Caucasians. The aim of this study was to evaluate vitamin D deficiency prevalence and its correlation to RA clinical parameters, and to determine the possible association of VDR gene polymorphisms and RA susceptibility in the Lithuanian population. Materials and Methods: Overall, 206 RA patients and 180 age- and sex-matched healthy controls were enrolled at Vilnius University Hospital Santaros Klinikos after informed consent was obtained. The disease activity score 28 C-reactive protein (DAS28 CRP), rheumatoid arthritis impact of disease (RAID) score, and health assessment questionnaire (HAQ) were recorded in RA patients, and 25(OH)D serum levels were evaluated by chemiluminescent microparticle immunoassay for all subjects. Four VDR gene polymorphisms, BsmI, FokI, ApaI, and TaqI, were assessed using real-time PCR instruments and genotyping assays in both groups. Results: The study registered a high prevalence of 25(OH)D deficiency (<50 nmol/L) in RA patients (61.55% (n = 127)). The mean serum concentration in RA patients (44.96 ± 21.92 (nmol/L)) was significantly lower than in the healthy controls (54.90 ± 22.82 (nmol/L)), p < 0.0001. A significant inverse correlation between vitamin D level, DAS28 CRP, and HAQ scores was confirmed in RA patients, with p < 0.05. Still, there was no significant association between the overall risk of RA disease for any allele or genotype of the four VDR loci tested. Conclusions: The study confirmed that vitamin D deficiency is prevalent among RA patients and the 25(OH)D level is significantly lower compared with healthy controls. Lower vitamin D concentration was related with increased disease activity and disability scores. However, genetic analysis of four VDR polymorphisms did not confer the susceptibility to RA in Lithuanian population.
33625044 Interstitial lung disease throughout the rheumatoid arthritis disease course. 2021 May 1 PURPOSE OF REVIEW: To summarize the current understanding of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) throughout the rheumatoid arthritis (RA) disease course from preclinical to established disease. RECENT FINDINGS: ILD is a serious extra-articular manifestation of RA. Multiple studies have demonstrated a high prevalence of both subclinical and clinical ILD throughout the RA disease course. Investigations of patients without RA have demonstrated an association between RA-related autoantibodies like anticitrullinated protein antibodies (ACPA) and interstitial abnormalities on lung imaging. A significant proportion of RA-ILD patients develop ILD prior to articular manifestations, suggesting that the lung plays a central role in RA development, perhaps through ACPA production. RA-ILD also occurs in early RA, when exuberant autoantibody production and systemic inflammation may propagate pulmonary disease activity. In patients with established RA, a high burden of subclinical and clinical ILD results in significant morbidity, mortality, and healthcare expenditure. Multiple epidemiologic and genetic risk factors, as well as serum biomarkers, have been associated with RA-ILD. SUMMARY: Subclinical and clinical ILD occur frequently in preclinical, early, and established RA and may play a key role in RA-related autoantibody production and disease progression. Further studies are needed to better understand the risk factors, prognosis, and potential therapies for RA-ILD.
33836352 Inhibition of regulator of G protein signaling 10, aggravates rheumatoid arthritis progres 2021 Jun Rheumatoid arthritis (RA) is the most common inflammatory arthropathy, with evidence pointing to an immune-mediated etiology that propagates chronic inflammation. Although targeted immune therapeutics and aggressive treatment strategies have substantially improved, a complete understanding of the associated pathological mechanisms of the disease remains elusive. This study aimed at investigating whether regulator of G protein signaling 10 (RGS10) could affect rheumatoid arthritis (RA) pathology by regulating the immune response. A DBA/J1 mouse model of RA was established and evaluated for disease severity. RGS10 expression was inhibited by adeno-associated virus in vivo. Moreover, small interfering RNA was used to downregulate RGS10 expression in raw 264.7 cells in vitro. Results showed that RGS10 inhibition augmented RA severity, and attenuated the increase in expression of inflammatory factors. Furthermore, activated NF-κB signaling pathways were detected following RGS10 inhibition. These results revealed that RGS10 inhibition directly aggravated the RA pathological process by activating the NF-κB signaling pathway. Therefore, RGS10 is a promising novel therapeutic target for RA treatment with a potential clinical impact.
32862311 Cognitive impairment in elderly patients with rheumatic disease and the effect of disease- 2021 Apr Recent development of biologic disease-modifying anti-rheumatic drugs (DMARDs) has led to better control of disease activity among patients with chronic rheumatological diseases. Many patients with rheumatic disease are living longer, adding to the growing elderly population. Rheumatic diseases, most notably rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), are known to increase the risk of cognitive impairment. Systemic inflammation associated with chronic rheumatological diseases has been postulated to be key driver of cognitive decline. Recent development of classic and biologic DMARDs have led to better control of disease activity among patients with rheumatic conditions. It is proposed that strict control of systemic inflammation will significantly lower the risk of cognitive impairment among patients with rheumatic disease. The impact of classic DMARDs on cognitive function appears to be variable. On the other hand, biologic DMARDs, specifically antitumor necrosis factor (TNF) drugs (i.e., etanercept), have been shown to significantly lower the risk of dementia. Experimental studies on IL-1, IL-6, and B and T cell blockade are promising. However, clinical data is limited. Preclinical studies on targeted therapies, specifically JAK/STAT inhibitors, also show promising results. Additional studies are necessary to better understand the impact of these newer biologic agents on cognitive function in elderly patients with rheumatic disease. Key points • Patients with chronic rheumatic conditions are beginning to live longer, adding to the elderly population. • Patients with chronic rheumatologic disease are at increased risk of cognitive impairment compared to the general population. • Recent development of biologic (i.e., TNF, IL-1, IL-6) and targeted drugs (i.e., Janus kinase inhibitors) have led to better control of disease activity. • Current evidence suggests that TNF inhibitors may have beneficial effects on cognitive function. However, evidence on newer biologic and targeted therapies is limited.
33926364 Factors affecting persistence with biologic treatments in patients with rheumatoid arthrit 2021 Sep Introduction: Biologic treatments are a milestone in the management of rheumatoid arthritis (RA) patients with an inadequate response to conventional synthetic treatments. With the increase in the number of biologic treatments, predictor factors of discontinuation are needed to choose the right treatment for the right patient.Areas covered: In this article, the factors affecting persistence with biologic treatments will be covered: factors associated with the demographic characteristics and comordidities of the patients, those with the characteristics of the disease, the biomarkers, and the adherence.Expert opinion: Seeking factors affecting persistence with biologic treatments is an important field of clinical research to offer the best management to the RA patients. Personalized medicine is the ultimate goal in this field to choose the biological therapy with the highest persistence for every patient. To achieve this goal, biomarkers could be a milestone.
34176880 Evaluation of Synovitis of Hand in Patients With Rheumatoid Arthritis Using Diffusion Kurt 2021 Jul OBJECTIVE: To explore the role of diffusion kurtosis magnetic resonance (MR) imaging in the noninvasive identification of synovitis in hand arthritis. METHODS: A total of 30 patients with rheumatoid arthritis (RA) and 10 patients suspected of RA were enrolled in the prospective study. A 3.0-T MR imaging including the diffusion kurtosis MR imaging sequence (b = 0, 500, 1000, 1500, 2000 s·mm2) was performed. A total of 210 regions of interest were confirmed and diffusion kurtosis MR imaging parameters were generated. The suspected synovitis or effusion was scored on a scale of 0 (effusion) to 3 (mild, moderate, severe synovitis), according to RA-MR imaging scoring system. The performance of diffusion kurtosis MR imaging parameters (the apparent diffusion coefficient [ADC], diffusion coefficient [D], and kurtosis [K]) in distinguishing different synovitis scores was evaluated. RESULTS: There were significant differences in ADC, D, and K values among different synovitis scores (all P < 0.001). Synovitis scores were negatively correlated with the ADC and D values significantly (r = -0.725, -0.757, respectively, all P < 0.001), but positively correlated with the K values significantly (r = 0.429, P < 0.001). The area under the curve values of D, ADC, and K values were 0.884, 0.874, and 0.728 for differentiating score 1-3 from score 0, respectively. Diffusion coefficient and ADC had similar diagnostic performance, and both were higher than K in detecting synovitis. No significant difference was found between the ADC and D values in detecting synovitis. CONCLUSIONS: The diffusion kurtosis MR imaging may be feasible as a noninvasive method for the diagnosis and grading of synovitis in the hands of RA patients, and the D and ADC values showed similar diagnostic performance, both of which were higher than K values.
33753821 Serum C-reactive protein metabolite (CRPM) is associated with incidence of contralateral 2021 Mar 22 The heterogeneous nature of osteoarthritis (OA) and the need to subtype patients is widely accepted in the field. The biomarker CRPM, a metabolite of C-reactive protein (CRP), is released to the circulation during inflammation. Blood CRPM levels have shown to be associated with disease activity and response to treatment in rheumatoid arthritis (RA). We investigated the level of blood CRPM in OA compared to RA using data from two phase III knee OA and two RA studies (N = 1591). Moreover, the association between CRPM levels and radiographic progression was investigated. The mean CRPM levels were significantly lower in OA (8.5 [95% CI 8.3-8.8] ng/mL, n = 781) compared to the RA patients (12.8 [9.5-16.0] ng/mL, n = 60); however, a significant subset of OA patients (31%) had CRPM levels (≥ 9 ng/mL) comparable to RA. Furthermore, OA patients (n = 152) with CRPM levels ≥ 9 ng/mL were more likely to develop contra-lateral knee OA assessed by X-ray over a two-year follow-up period with an odds ratio of 2.2 [1.0-4.7]. These data suggest that CRPM is a blood-based biochemical marker for early identification OA patients with an inflammatory phenotype.
34013997 Advances in Ultrasound Imaging in Rheumatology-What Do They Mean and What Challenges Do Th 2022 Mar Musculoskeletal ultrasound is an important tool for the monitorization of inflammatory rheumatic diseases, with subclinical synovitis being frequently detected in ultrasound scans of patients in clinical remission. It has been shown, for example, that the presence of Power Doppler signal synovial membrane has prognostic value for patients with rheumatoid arthritis. Microvascular imaging technologies significantly improve the sensitivity for slow-flow vessels and may potentially detect subclinical inflammation when Power Doppler fails to do so. The authors briefly discuss the implications of the use of such techniques in rheumatology setting and review available evidence.
33950231 Clinical use of Jak 1 inhibitors for rheumatoid arthritis. 2021 May 5 The uptake of Jak inhibitors in the RA space has been among the most rapid in rheumatology, based on the results of comprehensive clinical trial programmes of five agents. Newer generations of Jak inhibitors, like upadacitinib and filgotinib, target Jak 1 selectively with the aim of maximizing efficacy and to improve safety. This article will review the clinical significance of evidence on: (i) Jak 1 selectivity; (ii) efficacy from the SELECT and FINCH clinical trial programmes including patient intolerant or inadequately responding to MTX (MTX-IR) and other csDMARDs patients who are bDMARD-IR) and those using monotherapy when MTX is not tolerated or contraindicated and those treated when methotrexate naive; and (iii) safety from the clinical trial programmes of these two agents will be discussed.
34034155 Antigen-driven autoantibody production in lungs of interstitial lung disease with autoimmu 2021 Jul Interstitial lung disease (ILD) sometimes becomes a life-threatening complication of systemic autoimmune diseases; however, little is known about the immune response in lung lesions. We aimed to investigate humoural immunity in ILD associated with rheumatoid arthritis (RA), sjögren's syndrome (SjS), and mixed connective tissue disease (MCTD), using bronchoalveolar fluid (BALF) and serum samples from 15 patients with autoimmune disease associated-ILD. We first showed that BALF contained higher titers of disease-related autoantibodies than serum, suggesting the possibility of autoantibody production in lungs. Next, we produced 326 monoclonal antibodies from antibody-secreting cells in BALF, and the reactivity and their revertants, in which somatic hypermutations were reverted to germline, were analyzed. Among 123 antibodies from RA-ILD, 16 disease-related antibodies (anti-modified protein antibodies and rheumatoid factors) were identified, of which one antibody had both properties. The revertant antibodies changed their target modification in a complicated manner, suggesting that the antibodies were selected against various modifications in lungs. Among 146 antibodies from SjS-ILD and/or MCTD-ILD, seven anti-SSA/Ro60 antibodies and 15 anti-RNP antibodies were identified. Some of the anti-RNP antibodies recognized multiple RNP constituent proteins simultaneously, indicating that epitope spreading may progress in lungs. Our results revealed the existence of an active autoimmunity in the lungs of autoimmune disease associated-ILD.
33887489 Efficacy and safety of abatacept in interstitial lung disease of rheumatoid arthritis: A s 2021 Jun BACKGROUND: Interstitial lung disease (ILD) is a serious complication that represents the second leading cause of death in patients with rheumatoid arthritis (RA). Treatment of RA-ILD remains controversial. The absence of randomized clinical trials and specific ACR or EULAR therapeutic guidelines makes it difficult to establish solid therapeutic recommendations on this issue. In this scenario, real-world data is especially valuable. OBJECTIVE: To review the literature evidence on the efficacy and safety of abatacept (ABA) for the treatment of rheumatoid arthritis (RA) with associated interstitial lung disease (ILD), given its clinical relevance and the lack of consensus on its therapeutic management. METHODS: PUBMED and EMBASE were searched from the date of approval of ABA to the end of 2020 using a combination of RA, ILD and ABA terms following PRISMA guidelines. Identified studies were evaluated by two independent investigators. RESULTS: Nine original studies (1 case series and 8 observational studies) were selected for inclusion in the systematic review. No randomized trial or meta-analysis were identified. The mean age of patients ranged from 61.2 to 75 years and the mean RA duration varied from 7.4 to 18 years. Subcutaneous ABA (74.5%-91%) predominated in combination with conventional synthetic DMARDs (csDMARDs) (58%-75%), and it was used as first-line biologic agent in 22.8%-64.9% of the patients. The mean course of ILD ranged from 1 to 6.7 years, being usual and nonspecific interstitial pneumonia the most frequent patterns. Improvement or stabilization of ILD imaging (76.6%-92.7%) and FVC or DLCO (>85%) was described after a mean follow-up of 17.4-47.8 months, regardless of the pattern of lung involvement, being more remarkable in patients with shorter evolution of ILD. ABA led to significantly lower ILD worsening rates than TNF inhibitors (TNFi) and was associated with a 90% reduction in the relative risk of deterioration of ILD at 24 months of follow-up compared to TNFi and csDMARDs. Combination with methotrexate may have a corticoid-sparing effect. No unexpected adverse events were identified. CONCLUSIONS: Current evidence suggests that ABA may be a plausible alternative to treat RA patients with ILD. It would be highly desirable to develop prospective randomized controlled studies to confirm these findings.