Severe Extraarticular Manifestations in a Community-based Cohort of Patients with Rheumatoid Arthritis: Risk Factors and Incidence in Relation to Treatment with Tumor Necrosis Factor Inhibitors

Theander, Lisa; Nyhäll-Wåhlin, Britt Marie; Nilsson, Jan‐Åke; Willim, Minna; Jacobsson, Lennart; Petersson, Ingemar F; Turesson, Carl

doi:10.3899/jrheum.161103

Cited by 26 publications

(7 citation statements)

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“…First, a relatively small proportion of patients with RA-ILD was included, so we had to be conservative while building our models because of the risk of overfitting, so residual confounding cannot be ruled-out. Treatment and disease activity were not included; the former due to concerns about the accuracy of timing and dosing and current literature’s inability to validate a true relationship between RA-ILD and methotrexate45 or bDMARDs 46–48. The latter, because of the design of the study with only a single measurement, which has not shown to be relevant in previous reports,49 50 as opposed to its longitudinal evaluation 51.…”

Section: Discussionmentioning

confidence: 99%

Anti-carbamylated proteins antibody repertoire in rheumatoid arthritis: evidence of a new autoantibody linked to interstitial lung disease

et al. 2020

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ObjectiveTo analyse the association between anti-carbamylated protein antibodies (Anti-CarP) and interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients.MethodsCross-sectional study including RA patients fulfilling the 2010 ACR/EULAR criteria. The main population comprised two groups: (1) RA patients diagnosed with RA-ILD (RA-ILD group); (2) RA patients without ILD (non-ILD RA group). Non-ILD RA patients in whom ILD was suspected underwent a diagnostic work-up and, if ILD was diagnosed, were switched to the RA-ILD group. ILD was diagnosed by high-resolution computed tomography and confirmed by a multidisciplinary committee. An independent replication sample was also obtained. Three Anti-CarP IgG autoantibodies against fetal calf serum (Anti-FCS), fibrinogen (Anti-Fib) and chimeric fibrine/filagrine homocitrullinated peptide (Anti-CFFHP) and one Anti-CarP IgA against FCS (Anti-FCS-IgA) were determined by home-made ELISA. Associations between Anti-CarP and ILD were analysed using multivariable logistic regression adjusted by smoking, sex, age, RA disease duration, rheumatoid factor and anticitrullinated protein antibodies.ResultsWe enrolled 179 patients: 37 (21%) were finally diagnosed with RA-ILD. Anti-CarP specificities were more frequent in RA-ILD patients (Anti-FCS 70% vs 43%; Anti-Fib 73% vs 51%; Anti-CFFHP 38% vs 19%; Anti-CarP-IgA 51% vs 20%, p<0.05 for all comparisons). Serum titers of Anti-CarP were significantly higher in RA-ILD patients. Anti-CarP specificities showed a robust effect towards increasing the odds of ILD in the multivariate analysis (Anti-FCS (OR: 3.42; 95% CI: 1.13 to 10.40), Anti-Fib (OR: 2.85; 95% CI: 0.83 to 9.70), Anti-CFFHP (OR: 3.11; 95% CI: 1.06 to 9.14) and Anti-FCS-IgA (OR: 4.30; 95% CI: 1.41 to 13.04)). Similar findings were observed in the replication sample.ConclusionsAnti-CarP were strongly associated with ILD. The role of homocitrullination in RA-ILD merits further investigation.

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Section: Discussionmentioning

confidence: 99%

Anti-carbamylated proteins antibody repertoire in rheumatoid arthritis: evidence of a new autoantibody linked to interstitial lung disease

et al. 2020

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“…Bone destruction is primarily mediated by osteoclasts activated by ‘receptor activator of nuclear factor-κB’ (RANKL) and inflammatory cytokines in the synovial lining ( 10 ). If clinically manifested RA remains untreated or becomes treatment refractory, it can lead to extra-articular manifestations such as cardiovascular disease (CVD), interstitial lung disease, and increased risk of malignancy, due to increased immune complexes and acute phase response ( 37 ).…”

Section: Background: Rheumatoid Arthritismentioning

confidence: 99%

New Druggable Targets for Rheumatoid Arthritis Based on Insights From Synovial Biology

Sandhu

Thelma

2022

Front. Immunol.

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Rheumatoid arthritis (RA) is a multifactorial autoimmune disease characterized by chronic inflammation and destruction of multiple small joints which may lead to systemic complications. Altered immunity via pathogenic autoantibodies pre-date clinical symptom development by several years. Incompletely understood range of mechanisms trigger joint-homing, leading to clinically evident articular disease. Advances in therapeutic approaches and understanding pathogenesis have improved prognosis and likely remission. However, partial/non-response to conventional and biologic therapies witnessed in a subset of patients highlights the need for new therapeutics. It is now evident that joint disease chronicity stems from recalcitrant inflammatory synovial environment, majorly maintained by epigenetically and metabolically reprogrammed synoviocytes. Therefore, interference with effector functions of activated cell types seems a rational strategy to reinstate synovial homeostasis and complement existing anti-inflammatory interventions to mitigate chronic RA. Presenting this newer aspect of fibroblast-like synoviocytes and myeloid cells underlying the altered synovial biology in RA and its potential for identification of new druggable targets is attempted in this review. Major leads from i) molecular insights of pathogenic cell types from hypothesis free OMICS approaches; ii) hierarchy of their dysregulated signaling pathways; and iii) knowledge of druggability of molecular nodes in these pathways are highlighted. Development of such synovial biology-directed therapeutics hold promise for an enriched drug repertoire for RA.

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“…Myocarditis may be diffuse necrotizing or granulomatous. According to [ 18 ], the percentage of cardiomyopathy in patients with RA is believed to be 3–30%, discovered by autopsy. The precise etiopathogenesis of this disease is not fully understood, but some inflammatory cytokines (for example, interleukin (IL)-1α) and mediators are released from the degenerating myocardium, thus activating inflammatory corpuscles in other nearby cells [ 10 ].…”

Section: Cardiac Involvement In Rheumatoid Arthritismentioning

confidence: 99%

Ischemic Heart Disease and Rheumatoid Arthritis—Two Conditions, the Same Background

Rezuş

Macovei

Burlui

et al. 2021

Life

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Rheumatoid arthritis (RA) is one of the most frequent inflammatory rheumatic diseases, having a considerably increased prevalence of mortality and morbidity due to cardiovascular disease (CVD). RA patients have an augmented risk for ischemic and non-ischemic heart disease. Increased cardiovascular (CV) risk is related to disease activity and chronic inflammation. Traditional risk factors and RA-related characteristics participate in vascular involvement, inducing subclinical changes in coronary microcirculation. RA is considered an independent risk factor for coronary artery disease (CAD). Endothelial dysfunction is a precocious marker of atherosclerosis (ATS). Pro-inflammatory cytokines (such as TNFα, IL-1, and IL-6) play an important role in synovial inflammation and ATS progression. Therefore, targeting inflammation is essential to controlling RA and preventing CVD. Present guidelines emphasize the importance of disease control, but studies show that RA- treatment has a different influence on CV risk. Based on the excessive risk for CV events in RA, permanent evaluation of CVD in these patients is critical. CVD risk calculators, designed for the general population, do not use RA-related predictive determinants; also, new scores that take into account RA-derived factors have restricted validity, with none of them encompassing imaging modalities or specific biomarkers involved in RA activity.

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Severe Extraarticular Manifestations in a Community-based Cohort of Patients with Rheumatoid Arthritis: Risk Factors and Incidence in Relation to Treatment with Tumor Necrosis Factor Inhibitors

Abstract: This study suggests that patients treated with TNF inhibitors are at a slightly increased risk of developing severe ExRA. RF-positive patients with disabling disease of long duration were more likely to develop severe ExRA.

Cited by 26 publications

References 30 publications

Anti-carbamylated proteins antibody repertoire in rheumatoid arthritis: evidence of a new autoantibody linked to interstitial lung disease

Anti-carbamylated proteins antibody repertoire in rheumatoid arthritis: evidence of a new autoantibody linked to interstitial lung disease

New Druggable Targets for Rheumatoid Arthritis Based on Insights From Synovial Biology

Ischemic Heart Disease and Rheumatoid Arthritis—Two Conditions, the Same Background

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