scholarly journals Efficacy of pharmacological treatment in rheumatoid arthritis: a systematic literature research informing the 2019 update of the EULAR recommendations for management of rheumatoid arthritis

2020 ◽  
pp. annrheumdis-2019-216656 ◽  
Author(s):  
Andreas Kerschbaumer ◽  
Alexandre Sepriano ◽  
Josef S Smolen ◽  
Désirée van der Heijde ◽  
Maxime Dougados ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Residual Disease ◽  
Task Force ◽  
Certolizumab Pegol ◽  
Evidence Base ◽  
Janus Kinase ◽  
Cochrane Library ◽  
Literature Research ◽  
Eular Recommendations ◽  
Factor Inhibitor

ObjectivesTo inform the 2019 update of the European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA).MethodsA systematic literature research (SLR) to investigate the efficacy of any disease-modifying antirheumatic drug (DMARD) (conventional synthetic (cs)DMARD, biological (b) and biosimilar DMARD, targeted synthetic (ts)DMARD) or glucocorticoid (GC) therapy in patients with RA was done by searching MEDLINE, Embase and the Cochrane Library for articles published between 2016 and 8 March 2019.Results234 abstracts were selected for detailed assessment, with 136 finally included. They comprised the efficacy of bDMARDs versus placebo or other bDMARDs, efficacy of Janus kinase (JAK) inhibitors (JAKi) across different patient populations and head-to-head of different bDMARDs versus JAKi or other bDMARDs. Switching of bDMARDs to other bDMARDs or tsDMARDs, strategic trials and tapering studies of bDMARDs, csDMARDs and JAKi were assessed. The drugs evaluated included abatacept, adalimumab, ABT-122, baricitinib, certolizumab pegol, SBI-087, CNTO6785, decernotinib, etanercept, filgotinib, golimumab, GCs, GS-9876, guselkumab, hydroxychloroquine, infliximab, leflunomide, mavrilimumab, methotrexate, olokizumab, otilimab, peficitinib, rituximab, sarilumab, salazopyrine, secukinumab, sirukumab, tacrolimus, tocilizumab, tofacitinib, tregalizumab, upadacitinib, ustekinumab and vobarilizumab. The efficacy of many bDMARDs and tsDMARDs was shown. Switching to another tumour necrosis factor inhibitor (TNFi) or non-TNFi bDMARDs after TNFi treatment failure is efficacious. Tapering of DMARDs is possible in patients achieving long-standing stringent clinical remission; in patients with residual disease activity (including patients in LDA) the risk of flares is increased during the tapering. Biosimilars are non-inferior to their reference products.ConclusionThis SLR informed the task force regarding the evidence base of various therapeutic regimen for the development of the update of EULAR’s RA management recommendation.

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 Points to consider for the treatment of immune-mediated inflammatory diseases with Janus kinase inhibitors: a systematic literature research

RMD Open ◽  
2020 ◽  
Vol 6 (3) ◽  
pp. e001374
Author(s):  
Andreas Kerschbaumer ◽  
Josef S Smolen ◽  
Peter Nash ◽  
Thomas Doerner ◽  
Maxime Dougados ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Task Force ◽  
Inflammatory Diseases ◽  
Janus Kinase ◽  
Cochrane Library ◽  
Efficacy And Safety ◽  
Literature Research ◽  
Immune Mediated ◽  
Venous Thromboembolic Events

ObjectivesReview of efficacy and safety of Janus kinase (JAK) inhibition in immune-mediated inflammatory diseases (IMIDs).MethodsA systematic literature research (SLR) of all publications on JAK inhibitors (JAKi) treatment published until March 2019 using MEDLINE, EMBASE and the Cochrane Library. Efficacy and safety were assessed in randomised controlled trials (RCTs), integrating long-term extension periods additionally for safety evaluation.Results3454 abstracts were screened with 85 included in the final analysis (efficacy and RCT safety: n=72; safety only: n=13). Efficacy of RCTs investigating tofacitinib (TOFA, n=27), baricitinib (BARI, n=9), upadacitinib (UPA, n=14), filgotinib (FILGO, n=7), decernotinib (DEC, n=3) and peficitinib (PEF, n=7) was evaluated. Six head-to-head trials comparing JAKi with tumour necrosis factor inhibitors (TNFi) were included. Efficacy of JAKi was shown in rheumatoid arthritis (RA) for all agents, psoriatic arthritis (TOFA, FILGO), ankylosing spondylitis (TOFA, FILGO), systemic lupus erythematosus (BARI), chronic plaque psoriasis (TOFA, BARI, PEF), ulcerative colitis (TOFA, UPA), Crohn’s disease (UPA, FILGO) and atopic dermatitis (TOFA, BARI, UPA). Safety analysis of 72 RCTs, one cohort study and 12 articles on long-term extension studies showed increased risks for infections, especially herpes zoster, serious infections and numerically higher rates of venous thromboembolic events. No increased malignancy rates or major adverse cardiac events were observed.ConclusionJAKi provide good efficacy compared to placebo (and to TNFi in RA and Pso) across various IMIDs with an acceptable safety profile. This SLR informed the task force on points to consider for the treatment of IMIDs with JAKi with the available evidence.

scholarly journals EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis

2009 ◽  
Vol 69 (2) ◽  
pp. 325-331 ◽  
Author(s):  
M J L Peters ◽  
D P M Symmons ◽  
D McCarey ◽  
B A C Dijkmans ◽  
P Nicola ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Management ◽  
Inflammatory Arthritis ◽  
Task Force ◽  
Score Function ◽  
Cochrane Library ◽  
Expert Committee ◽  
Evidence Based ◽  
National Guidelines ◽  
Literature Research

Objectives:To develop evidence-based EULAR recommendations for cardiovascular (CV) risk management in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA).Methods:A multidisciplinary expert committee was convened as a task force of the EULAR Standing Committee for Clinical Affairs (ESCCA), comprising 18 members including rheumatologists, cardiologists, internists and epidemiologists, representing nine European countries. Problem areas and related keywords for systematic literature research were identified. A systematic literature research was performed using MedLine, Embase and the Cochrane library through to May 2008. Based on this literature review and in accordance with the EULAR’s “standardised operating procedures”, the multidisciplinary steering committee formulated evidence-based and expert opinion-based recommendations for CV risk screening and management in patients with inflammatory arthritis.Results:Annual CV risk assessment using national guidelines is recommended for all patients with RA and should be considered for all patients with AS and PsA. Any CV risk factors identified should be managed according to local guidelines. If no local guidelines are available, CV risk management should be carried out according to the SCORE function. In addition to appropriate CV risk management, aggressive suppression of the inflammatory process is recommended to further lower the CV risk.Conclusions:Ten recommendations were made for CV risk management in patients with RA, AS and PsA. The strength of the recommendations differed between RA on the one hand, and AS and PsA, on the other, as evidence for an increased CV risk is most compelling for RA.

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 SAT0052 THERAPEUTIC STRATEGIES IN DIFFICULT-TO-TREAT RHEUMATOID ARTHRITIS: PRELIMINARY RESULTS OF A SYSTEMATIC LITERATURE REVIEW INFORMING THE 2020 EULAR RECOMMENDATIONS FOR THE MANAGEMENT OF DIFFICULT-TO-TREAT RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 957-957
Author(s):  
N. M. T. Roodenrijs ◽  
A. Hamar ◽  
M. Kedves ◽  
G. Nagy ◽  
J. M. Van Laar ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Literature Review ◽  
Systematic Literature Review ◽  
Therapeutic Strategies ◽  
Eular Recommendations ◽  
Management Interventions ◽  
Fatigue Exercise ◽  
Factor Inhibitor ◽  
Management Recommendations ◽  
Sat 1

Background:Rheumatoid arthritis (RA) patients treated according to European League Against Rheumatism (EULAR) recommendations failing ≥2 biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) with a different mode of action who still have complaints which may be suggestive of active disease may be defined as suffering from ‘difficult-to-treat RA’. Management recommendations for RA focus predominantly on the earlier phases of the disease and specific recommendations for difficult-to-treat RA patients are currently lacking.1Objectives:To systematically summarise evidence in the literature on pharmacological and non-pharmacological therapeutic strategies for difficult-to-treat RA patients, informing the 2020 EULAR recommendations for the management of difficult-to-treat RA.Methods:A systematic literature review (SLR) was performed: PubMed, Embase and Cochrane databases were searched up to December 2019. Relevant papers were selected and appraised.Results:Thirty articles were selected for therapeutic strategies in patients with limited DMARD options due to contraindications, 73 for patients in whom previous b/tsDMARDs were not effective (‘true refractory RA’), and 51 for patients with predominantly non-inflammatory complaints. For patients with limited DMARD options, limited evidence was found on effective DMARD options for patients with concomitant obesity, and on safe DMARD options for patients with concomitant hepatitis B and C. In patients who failed ≥2 bDMARDs, tocilizumab, tofacitinib, baricitinib, upadacitinib and filgotinib were found to be more effective than placebo, but evidence was insufficient to prioritise. In patients who failed ≥1 bDMARD, there was a tendency of non-tumour necrosis factor inhibitor (TNFi) bDMARDs to be more effective than TNFi (Figure 1). Generally, b/tsDMARDs become less effective when patients failed more bDMARDs, this tendency was not clear for upadacitinib and filgotinib (Figure 2). In patients with predominantly non-inflammatory complaints (mainly function, pain and fatigue), exercise, education, psychological and self-management interventions were found to be of additional benefit.Conclusion:This SLR underscores the scarcity of evidence on the optimal treatment of difficult-to-treat RA patients. As difficult-to-treat RA is a newly defined disease state, all evidence is to an extent indirect. Several b/tsDMARDs were found to be effective in patients who failed ≥2 bDMARDs and generally effectiveness decreased with a higher number of failed bDMARDs. Additionally, a beneficial effect of non-pharmacological interventions was found on non-inflammatory complaints.References:[1] Smolen JSet al. Ann Rheum Dis2020. Epub ahead of print.Disclosure of Interests:Nadia M. T. Roodenrijs: None declared, Attila Hamar: None declared, Melinda Kedves: None declared, György Nagy: None declared, Jacob M. van Laar Grant/research support from: MSD, Genentech, Consultant of: MSD, Roche, Pfizer, Eli Lilly, BMS, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV, Paco Welsing: None declared

Current evidence for a strategic approach to the management of rheumatoid arthritis with disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis

2010 ◽  
Vol 69 (6) ◽  
pp. 987-994 ◽  
Author(s):  
R Knevel ◽  
M Schoels ◽  
T W J Huizinga ◽  
D Aletaha ◽  
G R Burmester ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Literature Review ◽  
Clinical Outcome ◽  
Physical Function ◽  
Systematic Literature Review ◽  
Structural Damage ◽  
Task Force ◽  
Treatment Strategies ◽  
Current Evidence ◽  
Eular Recommendations

ObjectivesTo perform a systematic literature review of effective strategies for the treatment of rheumatoid arthritis (RA).MethodsAs part of a European League Against Rheumatism (EULAR) Task Force investigation, a literature search was carried out from January 1962 until February 2009 in PubMed/Ovid Embase/Cochrane and EULAR/American College of Rheumatism (ACR)) abstracts (2007/2008) for studies with a treatment strategy adjusted to target a predefined outcome. Articles were systematically reviewed and clinical outcome, physical function and structural damage were compared between intensive and less intensive strategies. The results were evaluated by an expert panel to consolidate evidence on treatment strategies in RA.ResultsThe search identified two different kinds of treatment strategies: strategies in which the reason for treatment adjustment differed between the study arms (‘steering strategies’, n=13) and strategies in which all trial arms used the same clinical outcome to adjust treatment with different pharmacological treatments (‘medication strategies’, n=7). Both intensive steering strategies and intensive medication strategies resulted in better outcome than less intensive strategies in patients with early active RA.ConclusionIntensive steering strategies and intensive medication strategies produce a better clinical outcome, improved physical function and less structural damage than conventional steering or treatment. Proof in favour of any steering method is lacking and the best medication sequence is still not known.

scholarly journals Drug retention of 7 biologics and tofacitinib in biologics-naïve and biologics-switched patients with rheumatoid arthritis -The ANSWER cohort study-

2020 ◽  
Author(s):  
Kosuke Ebina ◽  
Toru Hirano ◽  
Yuichi Maeda ◽  
Wataru Yamamoto ◽  
Motomu Hashimoto ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Duration ◽  
Kinase Inhibitors ◽  
Proportional Hazards ◽  
Certolizumab Pegol ◽  
Cox Proportional Hazards ◽  
Janus Kinase ◽  
Retention Rates ◽  
Naive Group ◽  
Drug Retention

Abstract Background: This multi-center, retrospective study aimed to clarify retention rates and reasons for discontinuation of 7 biological disease-modifying antirheumatic drugs (bDMARDs) and tofacitinib (TOF), one of the janus kinase inhibitors, in bDMARDs-naïve and bDMARDs-switched patients with rheumatoid arthritis (RA).Methods: This study assessed 3,897 patients and 4,415 treatment courses with bDMARDs and TOF from 2001 to 2019 (2,737 bDMARDs-naïve patients and 1,678 bDMARDs-switched patients [59.5% switched to their second agent], female 82.3%, baseline age 57.4 years, disease duration 8.5 years; rheumatoid factor positivity 78.4%; Disease Activity Score in 28 joints using erythrocyte sedimentation rate 4.3; concomitant prednisolone [PSL] dose 6.1 mg/day [42.4%], and methotrexate [MTX] dose 8.5 mg/week [60.9%]). Treatment courses included abatacept (ABT; n=663), adalimumab (ADA; n=536), certolizumab pegol (CZP; n=226), etanercept (ETN; n=856), golimumab (GLM; n=458), infliximab (IFX; n=724), tocilizumab (TCZ; n=851), and TOF (n=101/only bDMARDs-switched cases). Drug retention rates and discontinuation reasons were estimated at 36 months using the Kaplan-Meier method and adjusted for potential clinical confounders (age, sex, disease duration, concomitant PSL and MTX, starting date, and number of switched bDMARDs) using Cox proportional hazards modeling.Results: Adjusted drug retention rates for each discontinuation reason were as follows: lack of effectiveness in the bDMARDs-naïve group (from 70.8% [CZP] to 85.1% [ABT]; P=0.001 between agents) and the bDMARDs-switched group (from 52.8% [CZP] to 78.7% [TCZ]; P<0.001 between agents). Toxic adverse events in the bDMARDs-naïve group (from 86.9% [IFX] to 96.3% [ABT]; P<0.001 between agents) and the bDMARDs-switched group (from 81.1% [ADA] to 95.4% [ETN]; P=0.01 between agents). Finally, overall retention rates excluding discontinuation for non-toxic reasons or remission ranged from 64.2% (IFX) to 82.0% (ABT) (P<0.001 between agents) in the bDMARDs-naïve group and from 44.2% (ADA) to 66.8% (TCZ) (P<0.001 between agents) in the bDMARDs-switched group. Conclusions: Remarkable differences were observed in drug retention of 7 bDMARDs and TOF between bDMARDs-naïve and bDMARDs-switched cases.

scholarly journals Pharmacological treatment of psoriatic arthritis: a systematic literature research for the 2019 update of the EULAR recommendations for the management of psoriatic arthritis

2020 ◽  
pp. annrheumdis-2020-217163 ◽  
Author(s):  
Andreas Kerschbaumer ◽  
Josef S Smolen ◽  
Maxime Dougados ◽  
Maarten de Wit ◽  
Jette Primdahl ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Cohort Studies ◽  
Case Control ◽  
Janus Kinase ◽  
Cochrane Library ◽  
Tnf Inhibitor ◽  
Efficacy And Safety ◽  
Case Control Studies ◽  
Literature Research ◽  
Venous Thromboembolic Events

ObjectiveTo perform an update of a review of the efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) in psoriatic arthritis (PsA).MethodsThis is a systematic literature research of 2015–2018 publications on all DMARDs in patients with PsA, searching Medline, Embase and the Cochrane Library. Efficacy was assessed in randomised controlled trials. For safety, cohort studies, case–control studies and long-term extensions (LTEs) were analysed.Results56 publications (efficacy: n=33; safety n=23) were analysed. The articles were on tumour necrosis factor (TNF) inhibitors (n=6; golimumab, etanercept and biosimilars), interleukin (IL)-17A inhibitors (n=10; ixekizumab, secukinumab), IL-23-p19 inhibitors (n=2; guselkumab, risankizumab), clazakizumab (IL-6 inhibitor), abatacept (CD80/86 inhibitor) and ABT-122 (anti-TNF/IL-17A), respectively. One study compared ustekinumab (IL-12/23i) with TNF inhibitor therapy in patients with entheseal disease. Three articles investigated DMARD tapering. Trials on targeted synthetic DMARDs investigated apremilast (phosphodiesterase-4 inhibitor) and Janus kinase inhibitors (JAKi; tofacitinib, filgotinib). Biosimilar comparison with bio-originator showed non-inferiority. Safety was evaluated in 13 LTEs, 9 cohort studies and 1 case–control study investigating malignancies, infections, infusion reactions, multiple sclerosis and major cardiovascular events, as well as efficacy and safety of vaccination. No new safety signals were identified; however, warnings on the risk of venous thromboembolic events including pulmonary embolism when using JAKi were issued by regulators based on other studies.ConclusionMany drugs in PsA are available and have demonstrated efficacy against placebo. Efficacy varies across PsA manifestations. Safety must also be taken into account. This review informed the development of the European League Against Rheumatism 2019 updated PsA management recommendations.

EULAR points to consider for conducting clinical trials in systemic lupus erythematosus: literature based evidence for the selection of endpoints: Table 1

2008 ◽  
Vol 68 (4) ◽  
pp. 477-483 ◽  
Author(s):  
G K Bertsias ◽  
J P A Ioannidis ◽  
J Boletis ◽  
S Bombardieri ◽  
R Cervera ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Clinical Trials ◽  
Literature Review ◽  
Outcome Measures ◽  
Lupus Erythematosus ◽  
Task Force ◽  
Evidence Base ◽  
Cochrane Library ◽  
Systemic Lupus ◽  
End Points

Objective:To assess available evidence on the use of end-points (outcome measures) in clinical trials in systemic lupus erythematosus (SLE), as a part of the development of evidence-based recommendations for points to consider in clinical trials in SLE.Methods:The European League Against Rheumatism (EULAR) Task Force on SLE comprised 19 specialists, a clinical epidemiologist and a research fellow. Key questions addressing the evidence for clinical trial end-points in SLE were compiled using the Delphi technique. A systematic search of the PubMed and Cochrane Library databases was performed using McMaster/Hedges clinical query strategies and an array of relevant terms. Evidence was categorised based on sample size and type of design, and the categories of available evidence were identified for each recommendation. The strength of recommendation was assessed based on the category of available evidence and agreement on the statements was measured across the 19 specialists.Results:Eight questions were generated regarding end-points for clinical trials. The evidence to support each proposition was evaluated. The literature review revealed that most outcome measures used in phase 2/3 trials in SLE have not been formally validated in clinical trials, although some indirect validation has been undertaken.Conclusion:This systematic literature review forms the evidence base considered in the development of the EULAR recommendations for end-points in clinical trials in SLE.

Current evidence for the management of rheumatoid arthritis with biological disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of RA

2010 ◽  
Vol 69 (6) ◽  
pp. 976-986 ◽  
Author(s):  
J L Nam ◽  
K L Winthrop ◽  
R F van Vollenhoven ◽  
K Pavelka ◽  
G Valesini ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bacterial Infection ◽  
Task Force ◽  
Certolizumab Pegol ◽  
Safety Data ◽  
Biological Agents ◽  
Current Evidence ◽  
Increased Risk ◽  
Conventional Dmards ◽  
Disease Modifying

ObjectivesTo review the evidence for the efficacy and safety of biological agents in patients with rheumatoid arthritis (RA) to provide data to develop treatment recommendations by the European League Against Rheumatism (EULAR) Task Force.MethodsMedline, Embase and Cochrane databases were searched for relevant articles on infliximab (IFX), etanercept (ETN), adalimumab (ADA), certolizumab-pegol (CZP), golimumab (GLM), anakinra (ANA), abatacept (ABT), rituximab (RTX) and tocilizumab (TCZ) published between 1962 and February 2009; published abstracts from the 2007–2008 American College of Rheumatology (ACR) and EULAR conference were obtained.Results87 articles and 40 abstracts were identified. In methotrexate (MTX) naïve patients, biological therapy with IFX, ETN, ADA, GLM or ABT has been shown to improve clinical outcomes (level of evidence 1B). In MTX/other synthetic disease-modifying antirheumatic drug (DMARD) failures all nine biological agents confer benefit (1B), with lower efficacy noted for ANA. RTX, ABT, TCZ and GLM demonstrate efficacy in tumour necrosis factor inhibitor (TNFi) failures (1B). Less evidence exists for switching between IFX, ETN and ADA (3B). Biological and MTX combination therapy is more efficacious than a biological agent alone (1B). A safety review shows no increased malignancy risk compared with conventional DMARDs (3B). TNFi are generally associated with an increased risk of serious bacterial infection, particularly within the first 6 months of treatment initiation; increased tuberculosis (TB) rates with TNFi are highest with the monoclonal antibodies (3B).ConclusionsThere is good evidence for the efficacy of biological agents in patients with RA. Safety data confirm an increased risk of bacterial infection and TB with TNFi compared with conventional DMARDs.

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