Risk profiling for a refractory course of rheumatoid arthritis

Bécède, Manuel; Alasti, Farideh; Gessl, Irina; Haupt, Lukas; Kerschbaumer, Andreas; Landesmann, Uriel; Loiskandl, Michaela; Supp, Gabriela; Smolen, Josef S; Aletaha, Daniel

doi:10.1016/j.semarthrit.2019.02.004

Cited by 76 publications

(61 citation statements)

References 28 publications

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“…Current smokers also were more prevalent in the active than the inactive group (37.5% vs 6.25%; P=0.08). These findings are consistent with other data indicating that females and smokers generally have less optimal responses to RA therapies [18][19][20]. Three patients in the controlled group were in spontaneous drug-free remission [21].…”

Section: Characteristics Of Study Groupssupporting

confidence: 91%

“…Despite these advances, significant numbers of RA patients do not respond satisfactorily to available therapies. Delay in initiating early effective intervention has been identified as a major risk factor for a refractory disease course [19]. At least 30% of patients who are initially treated with MTX do not have adequate disease control and will need addition of another agent, usually a biologic DMARD [25].…”

Section: Discussionmentioning

confidence: 99%

“…One model that was developed for prediction of inadequate response to MTX in the first year of disease included higher disease activity and current smoking as contributing factors [18]. It is also generally accepted that female sex predicts a course that is more refractory to treatment [19,20]. Patients positive for the HLA-DRB1 shared epitope generally have more severe disease, and appear to also have a poorer response to MTX [20].…”

Section: Discussionmentioning

confidence: 99%

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Peripheral Blood Gene Expression Signatures Identify Methotrexate Responders in Patients with Rheumatoid Arthritis

June

Feger

Nevin

et al. 2019

Preprint

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Background: Methotrexate (MTX) and biologic therapies have remarkably improved outcomes in patients with rheumatoid arthritis (RA). However, choices of therapeutic regimens in an individual patient remain empiric, resulting in a risk of delayed control of inflammation consequent joint damage. In previous studies we have shown that a large number of protein-coding genes are dysregulated in RA and that the expression levels of the majority of these dysregulated genes return to normal in patients who have control of disease after initiating MTX monotherapy. Furthermore, in vitro responses to MTX are rapid, suggesting that changes in expression could precede clinical outcome, and have prognostic value. The aim of the current study was to analyze whole blood gene expression for correlates of clinical responses to MTX, with the long-term objective of developing prognostic biomarkers.Methods: RA patients (N=32) and healthy controls (HC; N=8) were from the Investigation of Remission in Rheumatoid Arthritis (IRRA) cohort at Pennsylvania State M.S. Hershey Medical Center. The RA group included 16 patients with active disease and 16 with controlled disease; 8 patients in each group were currently being treated with MTX. Whole blood RNA profiling was carried out in the Penn State College of Medicine Genomics core laboratory. Transcript data were analyzed using clustering algorithms and pathways analysis software to determine relatedness of groups.Results: Patients with active RA showed patterns of gene dysregulation that were farther from HC values than RA patients with controlled disease, whether or not MTX was a current medication. Comparison of the four RA groups determined by activity levels and MTX use showed over-expression of genes in alpha/beta and gamma interferon pathways, especially in active RA patients not currently taking MTX, suggesting contributions to maintenance of active disease.Conclusion: Levels of genes that are expressed in peripheral blood of RA patients correlate with disease activity and also with MTX treatment status. Longitudinal studies to determine how early in the treatment course changes in gene expression levels are detectable will be of interest to determine the potential for development of prognostic biomarkers to guide therapeutic decisions.

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Section: Characteristics Of Study Groupssupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Peripheral Blood Gene Expression Signatures Identify Methotrexate Responders in Patients with Rheumatoid Arthritis

June

Feger

Nevin

et al. 2019

Preprint

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“…Another good example of activities is the EULAR initiative to provide recommendations for difficult-to-treat RA,124 which will address the question if a once established diagnosis continues to be correct and will point to distinctions between inflammatory and non-inflammatory symptoms when deciding about T2T. In this respect, it is important to note that we are encountering an increasing number of patients who are ‘refractory’ to treatment or ‘difficult to treat’,124 125 and for whom the current recommendations also apply, provided a correct diagnosis and assessment of ongoing disease activity have been made. A correct diagnosis is key for the correct application of recommendations and appropriate use of medicines,20 which in RA means to combat inflammation.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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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.

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“…For most of the patients, the symptoms of GA and Rheumatoid Arthritis(RA) are similar, so it is easy to ignore the condition and delay the optimal treatment time. Therefore, we also distinguished the two by the difference of biochemical indicators.Furthermore, principal component analysis (PCA), orthogonal partial least squares discrimination analysis (OPLS-DA), non-repetitive one-way ANOVA [18], correlation analysis [19] and multiple logistic regression analysis [20] were used to screen the important indicators affecting GA in each stage, and to distinguish GA and RA.Finally, multiple logistic regression was used to establish a clinical diagnosis model [21], so as to improve the success rate of clinical diagnosis and prediction.The overview of study design was indicated in Figure S1.…”

Section: Figure 1 Abridged General View Of the Evolution Of Gouty Armentioning

confidence: 99%

Establishment of A Clinical Diagnostic Model for Gouty Arthritis Based on Serum Biochemical Profile: A Prospective Study

Lyu

Ding

Yang

et al. 2020

Preprint

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Objective Gouty arthritis is a chronic disease caused by purine metabolism disorder. The progress of the disease is relatively clear, divided into four stages. Clinical judgment of the stage of gouty arthritis is generally based on blood uric acid levels, bursa fluid examination, there are false positive cases. This paper attempts to construct a clinical diagnostic model based on routine blood test data, so as to avoid tedious procedures such as cystic fluid examination and predict the development direction of the disease. Methods Serum samples from 579 patients were collected and divided into training set (379 cases) and validation set (200 cases). Through a series of multivariate statistical analysis and correlation analysis, 12 serum biochemical indicators were selected as risk factors for gouty arthritis to obtain the serum biochemical spectrum of gouty arthritis. Based on the biochemical indicators of 379 patients, the clinical diagnosis model of gouty arthritis was established and visualized with R language to predict the probability of patients at different stages, and the stage with the highest probability was used as the diagnosis result, and the evaluation model of 200 patients was used. Results The total ROC of the clinical diagnosis model was 0.95, and the Kappa coefficient of the clinical diagnosis model was 0.80. Conclusion This model can be applied to clinical prediction and basic research to improve the accuracy of gouty arthritis staging.

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Risk profiling for a refractory course of rheumatoid arthritis

Cited by 76 publications

References 28 publications

Peripheral Blood Gene Expression Signatures Identify Methotrexate Responders in Patients with Rheumatoid Arthritis

Peripheral Blood Gene Expression Signatures Identify Methotrexate Responders in Patients with Rheumatoid Arthritis

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

Establishment of A Clinical Diagnostic Model for Gouty Arthritis Based on Serum Biochemical Profile: A Prospective Study

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