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- Smolen, JS, et al.
(författare)
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EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update
- 2023
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 82:1, s. 3-18
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Tidskriftsartikel (refereegranskat)abstract
- To provide an update of the EULAR rheumatoid arthritis (RA) management recommendations addressing the most recent developments in the field.MethodsAn international task force was formed and solicited three systematic literature research activities on safety and efficacy of disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs). The new evidence was discussed in light of the last update from 2019. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned to and participants finally voted on the level of agreement with each item.ResultsThe task force agreed on 5 overarching principles and 11 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); GCs; biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab including biosimilars), abatacept, rituximab, tocilizumab, sarilumab and targeted synthetic (ts) DMARDs, namely the Janus kinase inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib. Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering in sustained clinical remission is provided. Safety aspects, including risk of major cardiovascular events (MACEs) and malignancies, costs and sequencing of b/tsDMARDs were all considered. Initially, MTX plus GCs is recommended and on insufficient response to this therapy within 3–6 months, treatment should be based on stratification according to risk factors; With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD should be added to the csDMARD; after careful consideration of risks of MACEs, malignancies and/or thromboembolic events tsDMARDs may also be considered in this phase. If the first bDMARD (or tsDMARD) fails, any other bDMARD (from another or the same class) or tsDMARD (considering risks) is recommended. With sustained remission, DMARDs may be tapered but should not be stopped. Levels of evidence and levels of agreement were high for most recommendations.ConclusionsThese updated EULAR recommendations provide consensus on RA management including safety, effectiveness and cost.
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- Zapata, SJ, et al.
(författare)
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GENETIC SUSCEPTIBILITY VARIANTS FOR RHEUMATOID ARTHRITIS ARE NOT ASSOCIATED WITH EARLY REMISSION; A MULTI-COHORT STUDY
- 2021
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 403-404
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Patients who achieve remission promptly could have a specific genetic risk profile that supports regaining immune tolerance. The identification of these genes could provide novel drug targets.Objectives:To test the association between RA genetic risk variants with achieving remission at 6 months.Methods:We computed genetic risk scores (GRS) comprising of the RA susceptibility variants1 and HLA-SE status separately in 4425 patients across eight datasets from inception cohorts. Remission was defined as DAS28CRP<2.6 at 6 months. Missing DAS28CRP values in patients were imputed using predictive mean matching by MICE. We first tested whether baseline DAS28CRP changed with increasing GRS using linear regression. Next, we calculated odds ratios for GRS and HLA-SE on remission using logistic regression. Heterogeneity of the outcome between datasets was mitigated by running inverse variance meta-analysis.Results:Evaluation of the complete dataset, baseline clinical variables did not differ between patients achieving remission and those who did not (Table 1). Distribution of GRS was consistent between datasets. Neither GRS nor HLA-SE was associated with baseline DAS2DAS (OR1.01; 95% CI 0.99-1.04). A fixed effect meta-analysis (Figure 1.) showed no significant effect of the GRS (OR 0.99; 95% CI 0.94-1.03) or HLA-SE (OR 0.8CRP87; 95% CI 0.75-1.01) on remission at 6 months.Table 1.Summary of the data separated by disease activity after 6 months.allRemission at 6 monthsNo remission at 6 monthsN4425*15582430Age, mean (sd)55.38 (13.87)5517 (14.09)55.62 (13.59)Female %68.98%65.43%70.73%ACPA+ %61.94%63.53%61.67%Baseline DAS28, mean (sd)4.76 (1.22)4.47 (1.23)5.1 (1.15)*not all patients had 6 months dataConclusion:In these combined cohorts, RA genetics risk variants are not associated with early disease remission. At baseline there was no difference in genetic risk between patients achieving remission or not. Studies encompassing other genetic variants are needed to elucidate the genetics of RA remission.References:[1]Knevel R et al. Sci Transl Med. 2020;12(545):eaay1548.Acknowledgements:This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777357, RTCure.This project has received funding from Pfizer Inc.Disclosure of Interests:Samantha Jurado Zapata: None declared, Marc Maurits: None declared, Yann Abraham Employee of: Pfizer, Erik van den Akker: None declared, Anne Barton: None declared, Philip Brown: None declared, Andrew Cope: None declared, Isidoro González-Álvaro: None declared, Carl Goodyear: None declared, Annette van der Helm - van Mil: None declared, Xinli Hu Employee of: Pfizer, Thomas Huizinga: None declared, Martina Johannesson: None declared, Lars Klareskog: None declared, Dennis Lendrem: None declared, Iain McInnes: None declared, Fraser Morton: None declared, Caron Paterson: None declared, Duncan Porter: None declared, Arthur Pratt: None declared, Luis Rodriguez Rodriguez: None declared, Daniela Sieghart: None declared, Paul Studenic: None declared, Suzanne Verstappen: None declared, Leonid Padyukov: None declared, Aaron Winkler Employee of: Pfizer, John D Isaacs: None declared, Rachel Knevel Grant/research support from: Pfizer
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| 7. |
- Meisters, Rachelle, et al.
(författare)
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EULAR/eumusc.net standards of care for rheumatoid arthritis : cross-sectional analyses of importance, level of implementation and care gaps experienced by patients and rheumatologists across 35 European countries
- 2020
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 79:11, s. 1423-1431
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Tidskriftsartikel (refereegranskat)abstract
- Objective As part of European League against Rheumatism (EULAR)/European Musculoskeletal Conditions Surveillance and Information Network, 20 user-focused standards of care (SoCs) for rheumatoid arthritis (RA) addressing 16 domains of care were developed. This study aimed to explore gaps in implementation of these SoCs across Europe. Methods Two cross-sectional surveys on the importance, level of and barriers (patients only) to implementation of each SoC (0-10, 10 highest) were designed to be conducted among patients and rheumatologists in 50 European countries. Care gaps were calculated as the difference between the actual and maximum possible score for implementation (ie, 10) multiplied by the care importance score, resulting in care gaps (0-100, maximal gap). Factors associated with the problematic care gaps (ie, gap≥30 and importance≥6 and implementation<6) and strong barriers (≥6) were further analysed in multilevel logistic regression models. Results Overall, 26 and 31 countries provided data from 1873 patients and 1131 rheumatologists, respectively. 19 out of 20 SoCs were problematic from the perspectives of more than 20% of patients, while this was true for only 10 SoCs for rheumatologists. Rheumatologists in countries with lower gross domestic product and non-European Union countries were more likely to report problematic gaps in 15 of 20 SoCs, while virtually no differences were observed among patients. Lack of relevance of some SoCs (71%) and limited time of professionals (66%) were the most frequent implementation barriers identified by patients. Conclusions Many problematic gaps were reported across several essential aspects of RA care. More efforts need to be devoted to implementation of EULAR SoCs.
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- Sharma-Oates, A, et al.
(författare)
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INCREASED BIOLOGICAL AGE IN MALE PARTICIPANTS OF SWEDISH AND UK RHEUMATOID ARTHRITIS COHORTS IS NOT LINKED TO DISEASE
- 2022
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 1177-1177
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Immunesenescence in the adaptive immune system, subsequent to thymic involution, results in compromised immunity and increased susceptibility to autoimmune disease and chronic inflammation. There are reports in the literature that immunesenescence, including thymic atrophy and telomere shortening, is accelerated in patients with rheumatoid arthritis (RA)1. What is unclear is whether RA includes accelerated biological ageing overall in addition to immune ageing which may help to explain the increased risk of age-related diseases in RA2. Recent studies have identified a set of DNA methylated sites across the genome that are highly correlated with chronological age and mortality, termed epigenetic clocks3,4 or DNAm age (DNAma), and can be used to determine an individual’s biological age.ObjectivesThe aim of our study is to determine if the biological epigenetic clocks of RA patients are accelerated.MethodsWe evaluated the Horvath3 and Hannum4 epigenetic clocks of control and RA patients using published DNAm data sets, accessions GSE42861 (EIRA, Swedish cohort of 342 RA patients and 328 non-RA controls) and E-MTAB-6988 (77 RA discordant monozygotic twins).ResultsWe did not detect significant differences between DNAma of RA and non-RA twins. Similarly, there were no significant differences between the DNAma of RA patients and controls from the Swedish EIRA cohort. However, we detected a significant acceleration in DNAma of male discordant twins, both RA and non-RA, by 5.4 years (p=3.29e-5) and 2.8 years (p=0.04) using the Hannum and Horvath clocks, respectively. Male participants, both control and RA patients, from the EIRA cohort also exhibited an accelerated DNAma, by 1.5 years (p=7.55e-5) using the Hannum clock but using the Horvath clock a significant DNAma acceleration, by 1.4 years (p=0.002) was detected in male RA patients from the EIRA cohort.ConclusionOverall, we detected a significant biological age acceleration in male participants from both RA and control groups and only found a significant difference between DNAma of Non-RA controls and RA patients for one of the epigenetic clocks. Further analysis using additional cohort data and biological clock algorithms is needed to confirm our findings.References[1]Goronzy, J.J. and Weyand CM (2001). Thymic function and peripheral T-cell homeostasis in rheumatoid arthritis. Trends Immunol. 22(5):251-5.[2]Meune C, et al. (2009) Trends in cardiovascular mortality in patients with rheumatoid arthritis over 50 years: a systematic review and meta-analysis of cohort studies. Rheumatol 48:1309-1313.[3]Horvath S (2013) DNA methylation age of human tissues and cell types. Genome Biol 14:R115.[4]Hannum G, et al (2013) Genome-wide Methylation Profiles Reveal Quantitative Views of Human Aging Rates. Mol Cell 49:359-367.AcknowledgementsThe study was funded by FOREUMDisclosure of InterestsNone declared
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