Objective
To develop updated guidelines for the pharmacologic management of rheumatoid arthritis.
Methods
We developed clinically relevant population, intervention, comparator, and outcomes (PICO) ...questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the certainty of evidence. A voting panel comprising clinicians and patients achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations.
Results
The guideline addresses treatment with disease‐modifying antirheumatic drugs (DMARDs), including conventional synthetic DMARDs, biologic DMARDs, and targeted synthetic DMARDs, use of glucocorticoids, and use of DMARDs in certain high‐risk populations (i.e., those with liver disease, heart failure, lymphoproliferative disorders, previous serious infections, and nontuberculous mycobacterial lung disease). The guideline includes 44 recommendations (7 strong and 37 conditional).
Conclusion
This clinical practice guideline is intended to serve as a tool to support clinician and patient decision‐making. Recommendations are not prescriptive, and individual treatment decisions should be made through a shared decision‐making process based on patients’ values, goals, preferences, and comorbidities.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objective
To develop updated guidelines for the pharmacologic management of rheumatoid arthritis.
Methods
We developed clinically relevant population, intervention, comparator, and outcomes (PICO) ...questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the certainty of evidence. A voting panel comprising clinicians and patients achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations.
Results
The guideline addresses treatment with disease‐modifying antirheumatic drugs (DMARDs), including conventional synthetic DMARDs, biologic DMARDs, and targeted synthetic DMARDs, use of glucocorticoids, and use of DMARDs in certain high‐risk populations (i.e., those with liver disease, heart failure, lymphoproliferative disorders, previous serious infections, and nontuberculous mycobacterial lung disease). The guideline includes 44 recommendations (7 strong and 37 conditional).
Conclusion
This clinical practice guideline is intended to serve as a tool to support clinician and patient decision‐making. Recommendations are not prescriptive, and individual treatment decisions should be made through a shared decision‐making process based on patients’ values, goals, preferences, and comorbidities.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objective
To examine the degree to which shared risk factors explain the relationship of periodontitis (PD) to rheumatoid arthritis (RA) and to determine the associations of PD and Porphyromonas ...gingivalis with pathologic and clinical features of RA.
Methods
Patients with RA (n = 287) and patients with osteoarthritis as disease controls (n = 330) underwent a standardized periodontal examination. The HLA–DRB1 status of all participants was imputed using single‐nucleotide polymorphisms from the extended major histocompatibility complex. Circulating anti–P gingivalis antibodies were measured using an enzyme‐linked immunosorbent assay, and subgingival plaque was assessed for the presence of P gingivalis using polymerase chain reaction (PCR). Associations of PD with RA were examined using multivariable regression.
Results
Presence of PD was more common in patients with RA and patients with anti–citrullinated protein antibody (ACPA)–positive RA (n = 240; determined using the anti–cyclic citrullinated peptide 2 anti–CCP‐2 test) than in controls (35% and 37%, respectively, versus 26%; P = 0.022 and P = 0.006, respectively). There were no differences between RA patients and controls in the levels of anti–P gingivalis or the frequency of P gingivalis positivity by PCR. The anti–P gingivalis findings showed a weak, but statistically significant, association with the findings for both anti–CCP‐2 (r = 0.14, P = 0.022) and rheumatoid factor (RF) (r = 0.19, P = 0.001). Presence of PD was associated with increased swollen joint counts (P = 0.004), greater disease activity according to the 28‐joint Disease Activity Score using C‐reactive protein level (P = 0.045), and higher total Sharp scores of radiographic damage (P = 0.015), as well as with the presence and levels of anti–CCP‐2 (P = 0.011) and RF (P < 0.001). The expression levels of select ACPAs (including antibodies to citrullinated filaggrin) were higher in patients with subgingival P gingivalis and in those with higher levels of anti–P gingivalis antibodies, irrespective of smoking status. Associations of PD with established seropositive RA were independent of all covariates examined, including evidence of P gingivalis infection.
Conclusion
Both PD and P gingivalis appear to shape the autoreactivity of RA. In addition, these results demonstrate an independent relationship between PD and established seropositive RA.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objective
Interstitial lung disease (ILD) is a frequent complication of rheumatoid arthritis (RA), occurring in up to 40% of patients during the course of their disease. Early diagnosis is critical, ...particularly given the shared clinicoepidemiologic features between advanced rheumatoid arthritis–associated ILD (RA‐ILD) and idiopathic pulmonary fibrosis (IPF). This study was undertaken to define the molecular basis of this overlap through comparative profiling of serum proteins in RA‐ILD and IPF.
Methods
Multiplex enzyme‐linked immunosorbent assays (ELISAs) were used to profile 45 protein biomarkers encompassing cytokines/chemokines, growth factors, and matrix metalloproteinases (MMPs) in sera obtained from RA patients with ILD and those without, individuals with IPF, and healthy controls. Levels of selected serum proteins were compared between patient subgroups using adjusted linear regression, principal component analysis (PCA), and least absolute shrinkage and selection operator (LASSO) modeling.
Results
Multiplex ELISA‐based assessment of sera from 2 independent cohorts (Veterans Affairs VA and Non‐VA) revealed a number of non‐overlapping biomarkers distinguishing RA‐ILD from RA without ILD (RA–no ILD) in adjusted regression models. Parallel analysis of sera from IPF patients also yielded a discriminatory panel of protein markers in models adjusted for age/sex/smoking, which showed differential overlap with profiles linked to RA‐ILD in the VA cohort versus the Non‐VA cohort. PCA revealed several distinct functional groups of RA‐ILD–associated markers that, in the VA cohort, encompassed proinflammatory cytokines/chemokines as well as 2 different subsets of MMPs. Finally, LASSO regression modeling in the Non‐VA and VA cohorts revealed distinct biomarker combinations capable of discriminating RA‐ILD from RA–no ILD.
Conclusion
Comparative serum protein biomarker profiling represents a viable method for distinguishing RA‐ILD from RA–no ILD and identifying population‐specific mediators shared with IPF.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
To determine whether RA and interstitial lung disease (ILD) severity measures are associated with survival in patients with RA-ILD.
We studied US veterans with RA-ILD participating in a multicentre, ...prospective RA cohort study. RA disease activity (28-joint DAS DAS28-ESR) and functional status (multidimensional HAQ MDHAQ) were collected longitudinally while pulmonary function tests (forced vital capacity FVC, diffusing capacity for carbon monoxide) were obtained from medical records. Vital status and cause of death were determined from the National Death Index and administrative data. Predictors of death were assessed using multivariable Cox regression models adjusting for age, sex, smoking status, ILD duration, comorbidity burden and medications.
We followed 227 RA-ILD participants (93% male and mean age of 69 years) over 1073 person-years. Median survival after RA-ILD diagnosis was 8.5 years. Respiratory diseases (28%) were the leading cause of death, with ILD accounting for 58% of respiratory deaths. Time-varying DAS28-ESR (adjusted hazard ratio aHR 1.21; 95% CI: 1.03, 1.41) and MDHAQ (aHR 1.85; 95% CI: 1.29, 2.65) were separately associated with mortality independent of FVC and other confounders. Modelled together, the presence of either uncontrolled disease activity (moderate/high DAS28-ESR) or FVC impairment (<80% predicted) was significantly associated with mortality risk. Those with a combination of moderate/high disease activity and FVC <80% predicted had the highest risk of death (aHR 4.43; 95% CI: 1.70, 11.55).
Both RA and ILD disease severity measures are independent predictors of survival in RA-ILD. These findings demonstrate the prognostic value of monitoring the systemic features of RA-ILD.
Ankylosing spondylitis is a chronic inflammatory disease characterized by inflammation of the sacroiliac joints and the spine that can lead to significant pain, immobility, and disability. The ...etiology and pathogenesis of ankylosing spondylitis are incompletely understood, though most patients carry the HLA-B*27 allele. The objective of this study was to evaluate DNA methylation changes in ankylosing spondylitis with the goal of revealing novel mechanistic insights into this disease.
Genome-wide DNA methylation analysis was performed in whole blood DNA samples using the Infinium MethylationEPIC array in patients with ankylosing spondylitis compared to age, sex, and race matched patients with osteoarthritis as a non-inflammatory disease control. We studied 24 patients with ankylosing spondylitis, including 12 patients who carry HLA-B*27 and 12 patients who are HLA-B*27 negative. DNA methylation analysis was performed with adjustment for blood cell composition in each sample.
We identified a total of 67 differentially methylated sites between ankylosing spondylitis patients and osteoarthritis controls. Hypermethylated genes found included GTPase-related genes, while hypomethylated genes included HCP5, which encodes a lncRNA within the MHC region, previously associated with genetic risk for psoriasis and toxic epidermal necrolysis. Carrying HLA-B*27 was associated with robust hypomethylation of HCP5, tubulin folding cofactor A (TBCA) and phospholipase D Family Member 6 (PLD6) in ankylosing spondylitis patients. Hypomethylation within HCP5 involves a CpG site that contains a single nucleotide polymorphism in linkage disequilibrium with HLA-B*27 and that controls DNA methylation at this locus in an allele-specific manner.
A genome-wide DNA methylation analysis in ankylosing spondylitis identified DNA methylation patterns that could provide potential novel insights into this disease. Our findings suggest that HLA-B*27 might play a role in ankylosing spondylitis in part through inducing epigenetic dysregulation.
•A genome-wide DNA methylation study in ankylosing spondylitis (AS) was performed.•DNA methylation changes in peripheral blood underlie ankylosing spondylitis.•HLA-B*27 is associated robust hypomethylation of HCP5, TBCA, and PLD6 in AS.•HLA-B*27 might play a pathogenic role in AS through inducing epigenetic dysregulation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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