Predictive ability, validity, and responsiveness of the multi-biomarker disease activity score in patients with rheumatoid arthritis initiating methotrexate

Luedders, Brent A.; Johnson, Tate M.; Sayles, Harlan; Thiele, Geoffrey M.; Mikuls, Ted R.; O'Dell, James Robert; England, Bryant R.

doi:10.1016/j.semarthrit.2020.05.019

Cited by 10 publications

(9 citation statements)

References 26 publications

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“…In a 2019 update of ACR guidance for measures of disease activity in patients with RA, the DAS28‐ESR and CDAI both achieved a consensus recommendation for preferred use in clinical practice. Although this is a report from a clinical trial, our results are consistent with the recent ACR guidance recommending the DAS28‐ESR and CDAI for use in measuring disease activity in clinical practice and with results of other RA treatments with different mechanisms of action (13–15). The reasons underlying our study's finding that the MBDA was not reliably responsive to changes in RA disease activity with multiple therapies are unclear.…”

Section: Discussionsupporting

confidence: 88%

Discrepancy Between Multibiomarker Disease Activity and Clinical Disease Activity Scores in Patients With Persistently Active Rheumatoid Arthritis

Fleischmann

Liu

Zhu

et al. 2022

Arthritis Care & Research

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Objective Responsive assessment of disease activity in patients who have rheumatoid arthritis (RA) is necessary to evaluate therapeutic efficacy and guide treatment. We compared the utility of the multibiomarker disease activity (MBDA) score in the assessment of RA disease activity with that of the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28‐ESR) score and the Clinical Disease Activity Index (CDAI) in a multicenter, randomized, placebo‐controlled trial of repository corticotropin injection (RCI) in patients with persistently active RA. Methods Patients received 80 units of RCI twice weekly during a 12‐week open‐label period; those who experienced low disease activity at week 12 were randomly assigned to receive either 80 units of RCI or placebo twice weekly during a 12‐week double‐blind period. Changes in disease activity (measured by DAS28‐ESR, CDAI, and MBDA scores) and correlations between MBDA scores and both DAS28‐ESR and CDAI scores were assessed. Results Changes from baseline in DAS28‐ESR and CDAI scores suggested that RCI therapy led to clinically meaningful improvements in disease activity, but improvements from baseline in MBDA scores were below the minimally important difference threshold. For the DAS28‐ESR and CDAI, correlations with total MBDA and individual component scores were generally low (r ≤ 0.3) and occasionally moderate (r > 0.3 but r < 0.5). Conclusion The results of the present study suggest overall MBDA scores are not sufficiently responsive for assessing RA disease activity after RCI therapy. These findings are consistent with those seen with other RA drugs and, although they are from a clinical trial, suggest the MBDA should not be a preferred disease activity measure in clinical practice.

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Section: Discussionsupporting

confidence: 88%

Discrepancy Between Multibiomarker Disease Activity and Clinical Disease Activity Scores in Patients With Persistently Active Rheumatoid Arthritis

Fleischmann

Liu

Zhu

et al. 2022

Arthritis Care & Research

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“…48 MBDA correlated with disease activity but not response to treatment. 28 The lack of prediction of MBDA to response to treatment was also previously demonstrated. 49 However, the response to treatment to be detected by a biomarker depends on the spectrum of disease activity from the peak to the point of remission.…”

Section: Discussionmentioning

confidence: 75%

“…27 Luedders B, et al, have shown that although the multibiomarker disease activity (MBDA) score moderately correlated with disease activity, it did not predict treatment response to methotrexate. 28 Another study by Baker J et al, demonstrated that adjusted and unadjusted MBDA score correlated similarly with clinical disease activity. Adjustment for leptin reduced the influence of adiposity, particularly among women but significantly estimated higher disease activity in thin men and women.…”

Section: Resultsmentioning

confidence: 97%

Biomarkers for the diagnosis and treatment of rheumatoid arthritis-a systematic review

Abdelhafiz¹,

Baker²,

galscow³

2021

Preprint

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Background Rheumatoid Arthritis (RA) is an autoimmune disease, symmetrically affecting the small joints. Biomarkers are tools that can be used in the diagnosis and monitoring of RA. Aim To systematically explore the role of the biomarkers: C-reactive protein (CRP), Rheumatoid factor (RF), Anti-cyclic citrullinated protein (Anti-CCP), 14-3-3η and the multi-biomarker disease activity (MBDA) score for the diagnosis and treatment of RA. Methods A systematic review of the English literature using four different databases was carried out. Results CRP>7.1 mg/L predicted poor conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) outcome in RA. Anti-CCP, CRP ≥0.3 mg/dL and RF predicted bone erosion and cartilage destruction. Combination of high 14-3-3η with RF and CRP improved the prediction of rapid erosion progression (REP). Anti-CCP was not associated with disease activity, but was associated with increased radiographic damage (r=0.46, p=0.048). RF was not associated with joint damage but correlated with ultrasound-detected bone erosion. 14-3-3η significantly correlated with inflammation, bone remodelling and osteoporosis in RA patients (p<0.05). 14 3 3η positively correlated with RA duration (p=0.003), disease activity and positive RF (P=0.025) and it distinguished early from established RA. Early MBDA scores correlated with later response in disease activity, after 6 and 12 weeks of treatment (p<0.05). MBDA score was able to differentiate between small differences in disease activity and predicted remission over one year period. Conclusion The investigated biomarkers are helpful tools in clinical practice for diagnosis, monitoring of treatment and predicting prognosis in RA patients. However, further research is still required to investigate novel biomarkers for the pre-treatment selection of potentially responsive patients before starting therapy for a precision medicine in this area.

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“…Patients excluded from the study included: patients with other rheumatic diseases (i.e., Sjogren's, SLE, and overlap connective tissue disease), pregnant or lactating women, women of childbearing age not practicing an effective method of contraception, patients with a history of alcohol abuse who are unwilling to abstain or limit alcohol consumption, and patients with cytopenias or abnormal hepatic or renal function at the time of screening. Healthy control plasma samples were collected from volunteers reporting well to excellent health [52]. All patients provided informed consent and the studies were conducted under the University of Nebraska Medical Center Institutional Review Board approved protocols.…”

Section: Patientsmentioning

confidence: 99%

Plasma Metabolome Normalization in Rheumatoid Arthritis Following Initiation of Methotrexate and the Identification of Metabolic Biomarkers of Efficacy

et al. 2021

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Methotrexate (MTX) efficacy in the treatment of rheumatoid arthritis (RA) is variable and unpredictable, resulting in a need to identify biomarkers to guide drug therapy. This study evaluates changes in the plasma metabolome associated with response to MTX in RA with the goal of understanding the metabolic basis for MTX efficacy towards the identification of potential metabolic biomarkers of MTX response. Plasma samples were collected from healthy control subjects (n = 20), and RA patients initiating MTX therapy (n = 20, 15 mg/week) before and after 16 weeks of treatment. The samples were analyzed by a semi-targeted metabolomic analysis, and then analyzed by univariate and multivariate methods, as well as an enrichment analysis. An MTX response was defined as a clinically significant reduction in the disease activity score in 28 joints (DAS-28) of greater than 1.2; achievement of clinical remission, defined as a DAS-28 < 2.6, was also utilized as an additional measure of response. In this study, RA is associated with an altered plasma metabolome that is normalized following initiation of MTX therapy. Metabolite classes found to be altered in RA and corrected by MTX therapy were diverse and included triglycerides (p = 1.1 × 10−16), fatty acids (p = 8.0 × 10−12), and ceramides (p = 9.8 × 10−13). Stratification based on responses to MTX identified various metabolites differentially impacted in responders and non-responders including glucosylceramides (GlcCer), phosphatidylcholines (PC), sphingomyelins (SM), phosphatidylethanolamines (PE), choline, inosine, hypoxanthine, guanosine, nicotinamide, and itaconic acid (p < 0.05). In conclusion, RA is associated with significant alterations to the plasma metabolome displaying at least partial normalization following 16 weeks of MTX therapy. Changes in multiple metabolites were found to be associated with MTX efficacy, including metabolites involved in fatty acid/lipid, nucleotide, and energy metabolism.

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Predictive ability, validity, and responsiveness of the multi-biomarker disease activity score in patients with rheumatoid arthritis initiating methotrexate

Cited by 10 publications

References 26 publications

Discrepancy Between Multibiomarker Disease Activity and Clinical Disease Activity Scores in Patients With Persistently Active Rheumatoid Arthritis

Discrepancy Between Multibiomarker Disease Activity and Clinical Disease Activity Scores in Patients With Persistently Active Rheumatoid Arthritis

Biomarkers for the diagnosis and treatment of rheumatoid arthritis-a systematic review

Plasma Metabolome Normalization in Rheumatoid Arthritis Following Initiation of Methotrexate and the Identification of Metabolic Biomarkers of Efficacy

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