scholarly journals EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update

2013 ◽  
Vol 73 (3) ◽  
pp. 492-509 ◽  
Author(s):  
Josef S Smolen ◽  
Robert Landewé ◽  
Ferdinand C Breedveld ◽  
Maya Buch ◽  
Gerd Burmester ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Task Force ◽  
Certolizumab Pegol ◽  
Treatment Strategies ◽  
Treat To Target ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Dmard Therapy ◽  
Eular Recommendations ◽  
Disease Modifying

In this article, the 2010 European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA) with synthetic and biological disease-modifying antirheumatic drugs (sDMARDs and bDMARDs, respectively) have been updated. The 2013 update has been developed by an international task force, which based its decisions mostly on evidence from three systematic literature reviews (one each on sDMARDs, including glucocorticoids, bDMARDs and safety aspects of DMARD therapy); treatment strategies were also covered by the searches. The evidence presented was discussed and summarised by the experts in the course of a consensus finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) were determined. Fourteen recommendations were developed (instead of 15 in 2010). Some of the 2010 recommendations were deleted, and others were amended or split. The recommendations cover general aspects, such as attainment of remission or low disease activity using a treat-to-target approach, and the need for shared decision-making between rheumatologists and patients. The more specific items relate to starting DMARD therapy using a conventional sDMARD (csDMARD) strategy in combination with glucocorticoids, followed by the addition of a bDMARD or another csDMARD strategy (after stratification by presence or absence of adverse risk factors) if the treatment target is not reached within 6 months (or improvement not seen at 3 months). Tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, biosimilars), abatacept, tocilizumab and, under certain circumstances, rituximab are essentially considered to have similar efficacy and safety. If the first bDMARD strategy fails, any other bDMARD may be used. The recommendations also address tofacitinib as a targeted sDMARD (tsDMARD), which is recommended, where licensed, after use of at least one bDMARD. Biosimilars are also addressed. These recommendations are intended to inform rheumatologists, patients, national rheumatology societies and other stakeholders about EULAR's most recent consensus on the management of RA with sDMARDs, glucocorticoids and bDMARDs. They are based on evidence and expert opinion and intended to improve outcome in patients with RA.

scholarly journals Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2013 update of the EULAR recommendations for the management of rheumatoid arthritis

2014 ◽  
Vol 73 (3) ◽  
pp. 516-528 ◽  
Author(s):  
Jackie L Nam ◽  
Sofia Ramiro ◽  
Cecile Gaujoux-Viala ◽  
Kaoru Takase ◽  
Mario Leon-Garcia ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Literature Review ◽  
Systematic Literature Review ◽  
Initial Treatment ◽  
Certolizumab Pegol ◽  
Treatment Strategies ◽  
Treat To Target ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Disease Modifying

ObjectivesTo update the evidence for the efficacy of biological disease-modifying antirheumatic drugs (bDMARD) in patients with rheumatoid arthritis (RA) to inform the European League Against Rheumatism(EULAR) Task Force treatment recommendations.MethodsMedline, Embase and Cochrane databases were searched for articles published between January 2009 and February 2013 on infliximab, etanercept, adalimumab, certolizumab-pegol, golimumab, anakinra, abatacept, rituximab, tocilizumab and biosimilar DMARDs (bsDMARDs) in phase 3 development. Abstracts from 2011 to 2012 American College of Rheumatology (ACR) and 2011–2013 EULAR conferences were obtained.ResultsFifty-one full papers, and 57 abstracts were identified. The randomised controlled trials (RCT) confirmed the efficacy of bDMARD+conventional synthetic DMARDs (csDMARDs) versus csDMARDs alone (level 1B evidence). There was some additional evidence for the use of bDMARD monotherapy, however bDMARD and MTX combination therapy for all bDMARD classes was more efficacious (1B). Clinical and radiographic responses were high with treat-to-target strategies. Earlier improvement in signs and symptoms were seen with more intensive initial treatment strategies, but outcomes were similar upon addition of bDMARDs in patients with insufficient response to MTX. In general, radiographic progression was lower with bDMARD use, mainly due to initial treatment effects. Although patients may achieve bDMARD- and drug-free remission, maintenance of clinical responses was higher with bDMARD continuation (1B), but bDMARD dose reduction could be applied (1B). There was still no RCT data for bDMARD switching.ConclusionsThe systematic literature review confirms efficacy of biological DMARDs in RA. It addresses different treatment strategies with the potential for reduction in therapy, particularly with early disease control, and highlights emerging therapies.

scholarly journals EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update

2020 ◽  
pp. annrheumdis-2019-216655 ◽  
Author(s):  
Josef S Smolen ◽  
Robert B M Landewé ◽  
Johannes W J Bijlsma ◽  
Gerd R Burmester ◽  
Maxime Dougados ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Task Force ◽  
Certolizumab Pegol ◽  
Janus Kinase ◽  
Sustained Remission ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Levels Of Evidence ◽  
Eular Recommendations ◽  
Disease Modifying

ObjectivesTo provide an update of the European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) management recommendations to account for the most recent developments in the field.MethodsAn international task force considered new evidence supporting or contradicting previous recommendations and novel therapies and strategic insights based on two systematic literature searches on efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) since the last update (2016) until 2019. A predefined voting process was applied, current levels of evidence and strengths of recommendation were assigned and participants ultimately voted independently on their level of agreement with each of the items.ResultsThe task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib). Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering on sustained clinical remission is provided. Cost and sequencing of b/tsDMARDs are addressed. Initially, MTX plus GCs and upon insufficient response to this therapy within 3 to 6 months, stratification according to risk factors is recommended. With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD or JAK inhibitor should be added to the csDMARD. If this fails, any other bDMARD (from another or the same class) or tsDMARD is recommended. On sustained remission, DMARDs may be tapered, but not be stopped. Levels of evidence and levels of agreement were mostly high.ConclusionsThese updated EULAR recommendations provide consensus on the management of RA with respect to benefit, safety, preferences and cost.

scholarly journals Efficacy of glucocorticoids, conventional and targeted synthetic disease-modifying antirheumatic drugs: a systematic literature review informing the 2016 update of the EULAR recommendations for the management of rheumatoid arthritis

2017 ◽  
Vol 76 (6) ◽  
pp. 1102-1107 ◽  
Author(s):  
Katerina Chatzidionysiou ◽  
Sharzad Emamikia ◽  
Jackie Nam ◽  
Sofia Ramiro ◽  
Josef Smolen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Literature Review ◽  
Systematic Literature Review ◽  
Treat To Target ◽  
Tight Control ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Eular Recommendations ◽  
Synthetic Dmards ◽  
Disease Modifying

ObjectivesTo perform a systematic literature review (SLR) informing the 2016 update of the recommendations for the management of rheumatoid arthritis (RA).MethodsAn SLR for the period between 2013 and 2016 was undertaken to assess the efficacy of glucocorticoids (GCs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and targeted synthetic DMARDs (tsDMARDs) (tofacitinib and baricitinib) in randomised clinical trials.ResultsFor GCs, four studies were included in the SLR. Patients without poor prognostic factors experienced benefit when GCs were added to methotrexate (MTX). Lower doses of GCs were similar to higher doses. For csDMARDs, two new studies comparing MTX monotherapy with combination csDMARD were included in the SLR. In the tREACH trial at the end of 12 months no difference between the groups in disease activity, functional ability and radiographic progression was seen, using principles of tight control (treat-to-target). In the CareRA trial, combination therapy with csDMARDs was not superior to MTX monotherapy and monotherapy was better tolerated.For tsDMARDs, tofacitinib and baricitinib were shown to be more effective than placebo (MTX) in different patient populations.ConclusionsAddition of GCs to csDMARD therapy may be beneficial but the benefits should be balanced against the risk of toxicity. Under tight control conditions MTX monotherapy is not less effective than combination csDMARDs, but better tolerated. Tofacitinib and baricitinib are efficacious in patients with RA, including those with refractory disease.

scholarly journals EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs

2010 ◽  
Vol 69 (6) ◽  
pp. 964-975 ◽  
Author(s):  
Josef S Smolen ◽  
Robert Landewé ◽  
Ferdinand C Breedveld ◽  
Maxime Dougados ◽  
Paul Emery ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Expert Opinion ◽  
Treatment Strategies ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Eular Recommendations ◽  
Evidence Strength ◽  
Synthetic Dmards ◽  
Disease Modifying ◽  
General Aspects

Treatment of rheumatoid arthritis (RA) may differ among rheumatologists and currently, clear and consensual international recommendations on RA treatment are not available. In this paper recommendations for the treatment of RA with synthetic and biological disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs) that also account for strategic algorithms and deal with economic aspects, are described. The recommendations are based on evidence from five systematic literature reviews (SLRs) performed for synthetic DMARDs, biological DMARDs, GCs, treatment strategies and economic issues. The SLR-derived evidence was discussed and summarised as an expert opinion in the course of a Delphi-like process. Levels of evidence, strength of recommendations and levels of agreement were derived. Fifteen recommendations were developed covering an area from general aspects such as remission/low disease activity as treatment aim via the preference for methotrexate monotherapy with or without GCs vis-à-vis combination of synthetic DMARDs to the use of biological agents mainly in patients for whom synthetic DMARDs and tumour necrosis factor inhibitors had failed. Cost effectiveness of the treatments was additionally examined. These recommendations are intended to inform rheumatologists, patients and other stakeholders about a European consensus on the management of RA with DMARDs and GCs as well as strategies to reach optimal outcomes of RA, based on evidence and expert opinion.

scholarly journals Rheumatoid arthritis: problems of treatment at the present stage

2018 ◽  
Vol 12 (4) ◽  
pp. 65-70
Author(s):  
N. V. Chichasova
Keyword(s):  
Rheumatoid Arthritis ◽  
Biologic Agents ◽  
Control Treatment ◽  
Treat To Target ◽  
Present Stage ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Synthetic Dmards ◽  
Disease Modifying ◽  
Set Up

The possibilities of rheumatoid arthritis therapy have been significantly expanded today. In addition to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biologic agents (BAs), and a targeted synthetic DMARD, a control treatment strategy has been put into practice.The paper demonstrates successes in the early prescription of csDMARD and the implementation of treat-to-target principles – to achieve the goal after 6 months in 50% of patients receiving subcutaneous methotrexate and 45% of those using a Leflunomide generic. During this therapy, there is a lower need for BAs and targeted synthetic DMARDs. The priority problem is to train general practitioners in methods for the early detection of RA and to set up schools for these patients.

scholarly journals Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2016 update of the EULAR recommendations for the management of rheumatoid arthritis

2017 ◽  
Vol 76 (6) ◽  
pp. 1113-1136 ◽  
Author(s):  
Jackie L Nam ◽  
Kaoru Takase-Minegishi ◽  
Sofia Ramiro ◽  
Katerina Chatzidionysiou ◽  
Josef S Smolen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Literature Review ◽  
Clinical Response ◽  
Dose Reduction ◽  
Systematic Literature Review ◽  
Phase Iii ◽  
Treat To Target ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Disease Modifying

ObjectivesTo update the evidence for the efficacy of biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) to inform European League Against Rheumatism (EULAR) Task Force treatment recommendations.MethodsMEDLINE, EMBASE and Cochrane databases were searched for phase III or IV (or phase II, if these studies were lacking) randomised controlled trials (RCTs) published between January 2013 and February 2016. Abstracts from the American College of Rheumatology and EULAR conferences were obtained.ResultsThe RCTs confirmed greater efficacy with a bDMARD+conventional synthetic DMARD (csDMARD) versus a csDMARDs alone (level 1A evidence). Using a treat-to-target strategy approach, commencing and escalating csDMARD therapy and adding a bDMARD in cases of non-response, is an effective approach (1B). If a bDMARD had failed, improvements in clinical response were seen on switching to another bDMARD (1A), but no clear advantage was seen for switching to an agent with another mode of action. Maintenance of clinical response in patients in remission or low disease activity was best when continuing rather than stopping a bDMARD, but bDMARD dose reduction or ‘spacing’ was possible, with a substantial proportion of patients achieving bDMARD-free remission (2B). RCTs have also demonstrated efficacy of several new bDMARDs and biosimilar DMARDs (1B).ConclusionsThis systematic literature review consistently confirmed the previously reported efficacy of bDMARDs in RA and provided additional information on bDMARD switching and dose reduction.

scholarly journals Immediate Effect of Baricitinib on Arthritis and Biological Disease-Modifying Antirheumatic Drug-Induced Psoriasis-Like Skin Lesions in Two Patients with Rheumatoid Arthritis

2021 ◽  
Vol 2021 ◽  
pp. 1-4
Author(s):  
Yoshifumi Tada ◽  
Nobuyuki Ono ◽  
Syuichi Koarada
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Certolizumab Pegol ◽  
Skin Lesions ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Drug Induced ◽  
Beneficial Effects ◽  
Disease Modifying ◽  
Disease Modifying Antirheumatic Drug

Biological disease-modifying antirheumatic drugs (bDMARDs) are very effective for treating rheumatoid arthritis (RA). However, they sometimes induce adverse events such as psoriasis-like skin lesions. We describe psoriasis-like skin lesions that developed simultaneously with an RA flare in patient 1 during treatment with abatacept and in patient 2 soon after starting certolizumab pegol. The skin lesions persisted in patient 2 despite stopping certolizumab. Baricitinib was initiated because of RA flare and resulted in immediate beneficial effects on arthritis as well as skin lesions. The RA went into remission in both patients, and the psoriasis-like skin lesions disappeared within four weeks (patient 1) and three months (patient 2).

scholarly journals Blood pro-resolving mediators are linked with synovial pathology and are predictive of DMARD responsiveness in rheumatoid arthritis

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Esteban A. Gomez ◽  
Romain A. Colas ◽  
Patricia R. Souza ◽  
Rebecca Hands ◽  
Myles J. Lewis ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Treatment Initiation ◽  
Plasma Concentrations ◽  
Docosapentaenoic Acid ◽  
Lipid Mediator ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Dmard Therapy ◽  
Disease Modifying ◽  
Learning Analysis

Abstract Biomarkers are needed for predicting the effectiveness of disease modifying antirheumatic drugs (DMARDs). Here, using functional lipid mediator profiling and deeply phenotyped patients with early rheumatoid arthritis (RA), we observe that peripheral blood  specialized pro-resolving mediator (SPM) concentrations are linked with both DMARD responsiveness and disease pathotype. Machine learning analysis demonstrates that baseline plasma concentrations of resolvin D4, 10S, 17S-dihydroxy-docosapentaenoic acid, 15R-Lipoxin (LX)A4 and n-3 docosapentaenoic-derived Maresin 1 are predictive of DMARD responsiveness at 6 months. Assessment of circulating SPM concentrations 6-months after treatment initiation establishes that differences between responders and non-responders are maintained, with a decrease in SPM concentrations in patients resistant to DMARD therapy. These findings elucidate the potential utility of  plasma SPM concentrations as biomarkers of DMARD responsiveness in RA.

Cervical Spine Involvement among Patients with Rheumatoid Arthritis Treated Actively with Treat-to-target Strategy: 10-year Results of the NEO-RACo Study

2019 ◽  
Vol 47 (8) ◽  
pp. 1160-1164 ◽  
Author(s):  
Tia Sandström ◽  
Vappu Rantalaiho ◽  
Timo Yli-Kerttula ◽  
Hannu Kautiainen ◽  
Timo Malmi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cervical Spine ◽  
Treatment Strategies ◽  
Treat To Target ◽  
Triple Combination ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Subaxial Subluxation ◽  
Long Run ◽  
Radiological Changes

Objective.To evaluate the development of radiological changes of the cervical spine in patients with rheumatoid arthritis (RA) in the NEO-RACo trial treated with an intensive, remission-targeted combination of conventional synthetic disease-modifying antirheumatic drugs (csDMARD) and additional infliximab (IFX) or placebo (PLA) for the first 6 months.Methods.Ninety-nine patients with early, DMARD-naive RA were treated with a triple combination of csDMARD and prednisolone, and randomized to double-blindly receive either IFX (FIN-RACo+IFX) or PLA (FIN-RACo+PLA) infusions during the first 6 months. After 2 years the treatment strategies became unrestricted, but the treatment goal was strict NEO-RACo remission. At the 10-year visit, radiographs of the cervical spine were taken of 85 patients (38 in the FIN-RACo+IFX group and 47 in the FIN-RACo+PLA group). The study was registered at ClinicalTrials.gov (NCT 00908089).Results.There were 4/85 patients (4.7%) with cervical spine involvement (CSI) by 10 years. Atlantoaxial subluxation was found in 2/85 patients (2.4%), both in the FIN-RACo+IFX group, and none in the FIN-RACo+PLA group. Atlantoaxial impaction was found in 1/85 patients (1.2%) in the FIN-RACo+IFX group. Subaxial subluxation was found in 1/85 patients (1.2%).Conclusion.Early and intensive remission-targeted treatment has reduced the incidence of CSI and our results show that intensive treatment also prevents its development in the long run.

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