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.
Background The 1980 classification criteria for systemic sclerosis (SSc) lack sensitivity in early SSc and limited cutaneous SSc. A joint ACR-EULAR committee was established to develop new classification criteria for SSc. Methods Using consensus methods, 23 candidate items were arranged in a multi-criteria additive point system with a threshold to classify cases as SSc. The classification system was reduced by clustering items, and simplifying weights. The system was tested by: a) determining specificity and sensitivity in SSc cases and controls with scleroderma-like disorders; b) validating against the combined view of a group of experts on a set of cases with or without SSc. Results Skin thickening of the fingers extending proximal to the MCPs is sufficient to be classified as SSc, if that is not present, seven additive items apply with varying weights for each: skin thickening of the fingers, finger tip lesions, telangiectasia, abnormal nailfold capillaries, interstitial lung disease or pulmonary arterial hypertension, Raynaud's phenomenon, and SSc-related autoantibodies. Sensitivity and specificity in the validation sample were 0.91 and 0.92 for the new classification criteria and 0.75 and 0.72 for the 1980 ARA classification criteria. All selected cases were classified in accordance with consensus-based expert opinion. All cases classified as SSc by the 1980 ARA criteria were classified with the new criteria, and several additional cases were now considered to be SSc. Conclusion The ACR-EULAR classification criteria for SSc performed better than the 1980 ARA Criteria for SSc and should allow for more patients to be classified correctly as SSc.
In this controlled trial involving patients with osteoarthritis of the knee, the outcomes after arthroscopic lavage or arthroscopic débridement were no better than those after a placebo procedure.
Objective. To examine mortality rates in the largest systemic lupus erythematosus (SLE) cohort ever assembled.Methods. Our sample was a multisite international SLE cohort (23 centers, 9,547 patients). Deaths were ascertained by vital statistics registry linkage. Standardized mortality ratio (SMR; ratio of deaths observed to deaths expected) estimates were calculated for all deaths and by cause. The effects of sex, age, SLE duration, race, and calendar-year periods were determined.Results. The overall SMR was 2.4 (95% confidence interval 2.3-2.5). Particularly high mortality was seen for circulatory disease, infections, renal disease, non-Hodgkin's lymphoma, and lung cancer. The highest SMR estimates were seen in patient groups character-
ObjectiveEarlier detection of pulmonary arterial hypertension (PAH), a leading cause of death in systemic sclerosis (SSc), facilitates earlier treatment. The objective of this study was to develop the first evidence-based detection algorithm for PAH in SSc.MethodsIn this cross-sectional, international study conducted in 62 experienced centres from North America, Europe and Asia, adults with SSc at increased risk of PAH (SSc for >3 years and predicted pulmonary diffusing capacity for carbon monoxide <60%) underwent a broad panel of non-invasive assessments followed by diagnostic right heart catheterisation (RHC). Univariable and multivariable analyses selected the best discriminatory variables for identifying PAH. After assessment for clinical plausibility and feasibility, these were incorporated into a two-step, internally validated detection algorithm. Nomograms for clinical practice use were developed.ResultsOf 466 SSc patients at increased risk of PAH, 87 (19%) had RHC-confirmed PAH. PAH was mild (64% in WHO functional class I/II). Six simple assessments in Step 1 of the algorithm determined referral to echocardiography. In Step 2, the Step 1 prediction score and two echocardiographic variables determined referral to RHC. The DETECT algorithm recommended RHC in 62% of patients (referral rate) and missed 4% of PAH patients (false negatives). By comparison, applying European Society of Cardiology/European Respiratory Society guidelines to these patients, 29% of diagnoses were missed while requiring an RHC referral rate of 40%.ConclusionsThe novel, evidence-based DETECT algorithm for PAH detection in SSc is a sensitive, non-invasive tool which minimises missed diagnoses, identifies milder disease and addresses resource usage.
The objective of this systematic literature review was to determine the association between cardiovascular events (CVEs) and antirheumatic drugs in rheumatoid arthritis (RA) and psoriatic arthritis (PsA)/psoriasis (Pso).Systematic searches were performed of MEDLINE, EMBASE and Cochrane databases (1960 to December 2012) and proceedings from major relevant congresses (2010–2012) for controlled studies and randomised trials reporting confirmed CVEs in patients with RA or PsA/Pso treated with antirheumatic drugs. Random-effects meta-analyses were performed on extracted data.Out of 2630 references screened, 34 studies were included: 28 in RA and 6 in PsA/Pso. In RA, a reduced risk of all CVEs was reported with tumour necrosis factor inhibitors (relative risk (RR), 0.70; 95% CI 0.54 to 0.90; p=0.005) and methotrexate (RR, 0.72; 95% CI 0.57 to 0.91; p=0.007). Non-steroidal anti-inflammatory drugs (NSAIDs) increased the risk of all CVEs (RR, 1.18; 95% CI 1.01 to 1.38; p=0.04), which may have been specifically related to the effects of rofecoxib. Corticosteroids increased the risk of all CVEs (RR, 1.47; 95% CI 1.34 to 1.60; p<0.001). In PsA/Pso, systemic therapy decreased the risk of all CVEs (RR, 0.75; 95% CI 0.63 to 0.91; p=0.003).In RA, tumour necrosis factor inhibitors and methotrexate are associated with a decreased risk of all CVEs while corticosteroids and NSAIDs are associated with an increased risk. Targeting inflammation with tumour necrosis factor inhibitors or methotrexate may have positive cardiovascular effects in RA. In PsA/Pso, limited evidence suggests that systemic therapies are associated with a decrease in all CVE risk.
Systemic sclerosis is a complex autoimmune disease characterized by a chronic and frequently progressive course and by extensive patient-to-patient variability. Like other autoimmune diseases, systemic sclerosis occurs more frequently in women, with a peak of onset in the fifth decade of life. The exact cause of systemic sclerosis remains elusive but is likely to involve environmental factors in a genetically primed individual. Pathogenesis is dominated by vascular changes; evidence of autoimmunity with distinct autoantibodies and activation of both innate and adaptive immunity; and fibrosis of the skin and visceral organs that results in irreversible scarring and organ failure. Intractable progression of vascular and fibrotic organ damage accounts for the chronic morbidity and high mortality. Early and accurate diagnosis and classification might improve patient outcomes. Screening strategies facilitate timely recognition of life-threatening complications and initiation of targeted therapies to halt their progression. Effective treatments of organ-based complications are now within reach. Discovery of biomarkers - including autoantibodies that identify patient subsets at high risk for particular disease complications or rapid progression - is a research priority. Understanding the key pathogenetic pathways, cell types and mediators underlying disease manifestations opens the door for the development of targeted therapies with true disease-modifying potential. For an illustrated summary of this Primer, visit: http://go.nature.com/lchkcA.
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