Evidence for treating rheumatoid arthritis to target: results of a systematic literature search

Objectives To summarise existing evidence on a target oriented approach for rheumatoid arthritis (RA) treatment. Methods We conducted a systematic literature search including all clinical trials testing clinical, functional, or structural values of a targeted treatment approach. Our search covered Medline, Embase and Cochrane databases until December 2008 and also conference abstracts (2007, 2008). Results The primary search yielded 5881 citations; after the selection process, 76 papers underwent detailed review. Of these, only seven strategic clinical trials were extracted: four studies randomised patients to routine or targeted treatment, two compared two different randomised targets and one compared targeted treatment to a historical control group. Five trials dealt with early RA patients. All identified studies showed significantly better clinical outcomes of targeted approaches than routine approaches. Disability was reported in two studies with no difference between groups. Four studies compared radiographic outcomes, two showing significant benefit of the targeted approach. Conclusion Only few studies employed randomised controlled settings to test the value of treatment to a specific target. However, they provided unanimous evidence for benefits of targeted approaches. Nevertheless, more data on radiographic and functional outcomes and on patients with established RA are needed

Rapid Response to Remdesivir in Hospitalised COVID-19 Patients:A Propensity Score Weighted Multicentre Cohort Study

Introduction: Remdesivir is a registered treatment for hospitalised patients with COVID-19 that has moderate clinical effectiveness. Anecdotally, some patients’ respiratory insufficiency seemed to recover particularly rapidly after initiation of remdesivir. In this study, we investigated if this rapid improvement was caused by remdesivir, and which patient characteristics might predict a rapid clinical improvement in response to remdesivir. Methods: This was a multicentre observational cohort study of hospitalised patients with COVID-19 who required supplemental oxygen and were treated with dexamethasone. Rapid clinical improvement in response to treatment was defined by a reduction of at least 1 L of supplemental oxygen per minute or discharge from the hospital within 72 h after admission. Inverse probability of treatment-weighted logistic regression modelling was used to assess the association between remdesivir and rapid clinical improvement. Secondary endpoints included in-hospital mortality, ICU admission rate and hospitalisation duration. Results: Of 871 patients included, 445 were treated with remdesivir. There was no influence of remdesivir on the occurrence of rapid clinical improvement (62% vs 61% OR 1.05, 95% CI 0.79–1.40; p = 0.76). The in-hospital mortality was lower (14.7% vs 19.8% OR 0.70, 95% CI 0.48–1.02; p = 0.06) for the remdesivir-treated patients. Rapid clinical improvement occurred more often in patients with low C-reactive protein (≤ 75 mg/L) and short duration of symptoms prior to hospitalisation (&lt; 7 days) (OR 2.84, 95% CI 1.07–7.56). Conclusion: Remdesivir generally does not increase the incidence of rapid clinical improvement in hospitalised patients with COVID-19, but it might have an effect in patients with short duration of symptoms and limited signs of systemic inflammation.</p

HLA-B*08 identified as the most associated MHC locus for anti-carbamylated protein antibody-positive/anti-CCP-negative rheumatoid arthritis

Objective: Previously, only the HLA-DRB1 alleles have been assessed in rheumatoid arthritis (RA). The aim of the present study was to identify the key major histocompatibility complex (MHC) susceptibility factors showing a significant association with anti-carbamylated protein antibody-positive (anti-CarP+) RA. Methods: Analyses were restricted to RA patients who were anti-cyclic citrullinated peptide antibody negative (anti-CCP-), because the anti-CCP status dominated the results otherwise. Therefore, we studied samples from 1,821 anti-CCP- RA patients and 6,821 population controls from Spain, Sweden, and the Netherlands. The genotypes for ~8,000 MHC biallelic variants were assessed by dense genotyping and imputation. Their association with the anti-CarP status in RA patients was tested with logistic regression and combined with inverse-variance meta-analysis. Significance of the associations was assessed according to a study-specific threshold of P < 2.0 × 10-5 . Results: The HLA-B*08 allele and its correlated amino acid variant Asp-9 showed a significant association with anti-CarP+/anti-CCP- RA (P < 3.78 × 10-7 ; I2 = 0). This association was specific when assessed relative to 3 comparator groups: population controls, anti-CarP-/anti-CCP- RA patients, and anti-CCP- RA patients who were positive for other anti-citrullinated protein antibodies. Based on these findings, anti-CarP+/anti-CCP- RA patients could be separated from other antibody-defined subsets of RA patients in whom an association with the HLA-B*08 allele has been previously demonstrated. No other MHC variant remained associated with anti-CarP+/anti-CCP- RA after accounting for the presence of the HLA-B*08 allele. Specifically, the reported association of HLA-DRB1*03 was observed at a level comparable to that reported previously, but it was attributable to linkage disequilibrium. Conclusion: These results identify HLA-B*08 carrying Asp-9 as the MHC locus showing the strongest association with anti-CarP+/anti-CCP- RA. This knowledge may help clarify the role of the HLA in susceptibility to specific subsets of RA, by shaping the spectrum of RA autoantibodies. © 2020, American College of Rheumatology

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

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

Implementation of the hyaluronic acid fat graft myringoplasty technique, pitfalls and lessons learned

textabstractBackground: Myringoplasty is a common procedure in otorhinolaryngology. Many techniques with different complications and outcomes have been described, one of which is hyaluronic acid fat graft myringoplasty (HAFGM). This technique, as proposed by Saliba, uses fat tissue and hyaluronic acid discs. The technique is relatively fast with a high success rate and low complications. However, what outcomes can be expected when performed by other surgeons? In this paper, we report on the technique’s success in our own hands. Materials and methods: Based on Saliba’s protocol, we performed 86 HAFGMs by a transcanal approach between 2012 and August 2014. However, our 70% success rate was significantly different from Saliba’s 92% (p value 2.8e − 05). We visited Saliba’s clinic in order to identify critical differences between our approaches. We adapted the differences we found in our protocol and analysed another 50 HAFGMs performed afterwards, between October 2014 and December 2015. Results: The success rate increased to 86–89%, this percentage is not different compared to Saliba’s results (p value .25 and .54). Conclusion: HAFGM is a reproducible technique in the hands of other surgeons, but critical following of the surgical protocol is important

Defining erosive disease typical of RA in the light of the ACR/EULAR 2010 criteria for rheumatoid arthritis; results of the data driven phase.

International audienceAccording to the 2010 criteria, rheumatoid arthritis (RA) can be classified in the presence of ≥6 points on the criteria or 'typical' erosive disease. RA-specific erosiveness however has not been defined yet. This study reports the results of the data driven phase of a European League Against Rheumatism (EULAR) taskforce aiming to define RA-specific erosiveness.Baseline radiographs of hands and feet of 980 Dutch and 811 French early arthritis patients were studied on the number and site of erosive joints. Test characteristics were determined, with the outcome measures being initiation of methotrexate (MTX) therapy or any disease modifying antirheumatic drug (DMARD) therapy within the first year of disease and arthritis persistency over 5 years. Analyses were repeated in the patients with 50% for ≥1 erosive joint, >80% for ≥3 erosive joints and >90% for ≥5 erosive joints. When analysing the patients not fulfilling the 2010 criteria (n=308 and 149), specificity was >60% for ≥1 erosive joint, >90% for ≥3 erosive joints and >95% for ≥5 erosive joints. Few of these patients fulfilled the radiological criterion; 27-36 patients had ≥3 erosive joints and 13-14 patients had ≥5 erosive joints.RA-specific erosiveness can be defined with high specificity at several cut-offs for the number of erosive joints in two independent cohorts with multiple different outcomes. The final radiological criterion will be established in the next phase

Evaluation of the contribution of cumulative levels of inflammation to the variance in joint destruction in rheumatoid arthritis

Development and application of statistical models for medical scientific researc

Genetic predisposition of the severity of joint destruction in rheumatoid arthritis: a population-based study.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.The susceptibility to rheumatoid arthritis (RA) is partly heritable, but whether the severity of RA is also influenced by genetics has not been determined. The evaluation of the heritability of the severity of RA is basic to further studies on genetic factors. A study was undertaken to determine whether joint destruction is heritable. Iceland has an unique comprehensive genealogy database covering today's population and stretching back to ≥1000 years ago, as well as genome-wide single nucleotide polymorphism data for a large part of the population. Hand and feet x-rays of 325 Icelandic patients with RA were scored according to the Sharp-van der Heijde method. The degree of relatedness between patients was estimated in two ways: (1) kinship coefficients (KC) on the genealogical data were expressed; and (2) the identical-by-descent (IBD) was estimated applying long-range phasing of the genetic profile of the patients. The degree of relatedness was tested against the similarity in joint destruction rates by linear regression analysis and the heritability of joint destruction was calculated. Significant associations between degree of relatedness and similarity in joint destruction rates were observed for both methods of determining relatedness (p(KC)=0.018, p(IBD)=0.003). The estimated heritability was 45% using KC and 58% using the estimated IBD data. The severity of joint destruction in RA is influenced by genetic factors.Dutch Arthritis Foundation, Reumafonds Netherlands Organisation of Health Research and Development (ZonMw

New risk model is able to identify patients with a low risk of progression in systemic sclerosis

Objectives To develop a prediction model to guide annual assessment of systemic sclerosis (SSc) patients tailored in accordance to disease activity.Methods A machine learning approach was used to develop a model that can identify patients without disease progression. SSc patients included in the prospective Leiden SSc cohort and fulfilling the ACR/EULAR 2013 criteria were included. Disease progression was defined as progression in ≥1 organ system, and/or start of immunosuppression or death. Using elastic-net-regularisation, and including 90 independent clinical variables (100% complete), we trained the model on 75% and validated it on 25% of the patients, optimising on negative predictive value (NPV) to minimise the likelihood of missing progression. Probability cutoffs were identified for low and high risk for disease progression by expert assessment.Results Of the 492 SSc patients (follow-up range: 2–10 years), disease progression during follow-up was observed in 52% (median time 4.9 years). Performance of the model in the test set showed an AUC-ROC of 0.66. Probability score cutoffs were defined: low risk for disease progression (&lt;0.197, NPV:1.0; 29% of patients), intermediate risk (0.197–0.223, NPV:0.82; 27%) and high risk (&gt;0.223, NPV:0.78; 44%). The relevant variables for the model were: previous use of cyclophosphamide or corticosteroids, start with immunosuppressive drugs, previous gastrointestinal progression, previous cardiovascular event, pulmonary arterial hypertension, modified Rodnan Skin Score, creatine kinase and diffusing capacity for carbon monoxide.Conclusion Our machine-learning-assisted model for progression enabled us to classify 29% of SSc patients as ‘low risk’. In this group, annual assessment programmes could be less extensive than indicated by international guidelines