Brief Report: Enhancement of Patient Recruitment in Rheumatoid Arthritis Clinical Trials Using a Multi‐Biomarker Disease Activity Score as an Inclusion Criterion

Abstract

ObjectiveRheumatoid arthritis (RA) clinical trials often exclude patients who have low C‐reactive protein (CRP) levels, which slows enrollment into the trial. The purpose of this study was to determine whether high Multi‐Biomarker Disease Activity (MBDA) scores (>44) in RA patients with low CRP levels (≤10 mg/liter) could be used as a complement to CRP levels >10 mg/liter to enhance patient recruitment without affecting clinical trial outcomes.MethodsWe evaluated patients from the Swedish Pharmacotherapy (SWEFOT) trial, which did not include any selection criteria for CRP levels. Clinical outcomes were assessed after 3 months of methotrexate (MTX) monotherapy in MTX‐naive RA patients (n = 220) and after 3–10 months of add‐on therapy in patients who were incomplete responders to MTX alone (MTX‐IR) (n = 127). Radiographic outcomes were assessed at 1 year in all patients. Within each cohort, the outcomes were compared between patients with a CRP level of ≤10 mg/liter and an MBDA score of >44 at the start of the respective treatment interval versus those with a CRP level of >10 mg/liter.ResultsPatients with both a CRP level of ≤10 mg/liter and an MBDA score of >44 at baseline had clinical and radiographic outcomes that were comparable to those in patients with a CRP level of >10 mg/liter at baseline. This broadened definition of the inclusion criteria identified an additional 24% of patients in the MTX‐naive cohort and 47% in the MTX‐IR cohort.ConclusionPatient recruitment into RA clinical trials may be substantially enhanced, without any decrease in clinical and radiographic outcomes, by using as an inclusion criterion “a CRP level of >10 mg/liter and/or an MBDA score of >44.”

Correlation of the Multi‐Biomarker Disease Activity Score With Rheumatoid Arthritis Disease Activity Measures: A Systematic Review and Meta‐Analysis

“…Our search strategy identified an initial 718 studies, with 470 remaining after excluding duplicates (Figure ). Full‐text review of 121 studies was completed with exclusion of those reported only in abstract form (n = 98) or without original data (n = 1), resulting in 22 articles included in the systematic review . Eight studies showed correlations with RA disease activity measures and were included in the meta‐analyses .…”

“…In a separate analysis from the SWEFOT trial, patients with high MBDA scores receiving triple therapy were more likely to have RP after 2 years of follow‐up than patients receiving MTX and infliximab . Additional outcomes reported on the MBDA included its potential to increase recruitment to clinical trials (i.e., identifying patients with low CRP who would otherwise be excluded) , as well as its ability to predict disease relapse .…”

Ultrasound and multi-biomarker disease activity score for assessing and predicting clinical response to tofacitinib treatment in patients with rheumatoid arthritis

“…If baseline measures or their early changes suggest possible treatment failure, an earlier change of treatment could be considered, potentially improving the clinical course and minimizing unnecessary healthcare utilization. In addition, elevated baseline MSUS and/or MBDA scores may provide value as inclusion criteria in randomized clinical trials allowing for a more homogenous group of RA patients with high disease activity and risk for joint damage [37].…”

“…The biomarkers in the MBDA test reflect the biology of RA and consist of cytokine-related proteins (IL-6, TNF-R1), acute phase reactants (CRP, serum amyloid A), an adhesion molecule (VCAM-1), growth factors (EGF, VEGF-A), matrix metalloproteinases (MMP-1, MMP-3), and adipokines (leptin, resistin). The MBDA score is an integer on a scale of 1 to 100, with disease activity categories of low (< 30), moderate (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44) and high (> 44) [10]. Minimally clinically important difference (MCID) for MBDA score is ≥8 [23].…”

Reanalysis of the Multi‐Biomarker Disease Activity Score for Assessing Disease Activity in the Abatacept Versus Adalimumab Comparison in Biologic‐Naive Rheumatoid Arthritis Subjects with Background Methotrexate Study: Comment on the Article by Fleischmann et al

“…We would encourage readers to make the distinction between the scientific validity of a diagnostic test and its clinical utility. There is already a sizable evidence base supporting the development and validation of the MBDA test in diverse RA patient cohorts (9)(10)(11)(12)(13)(18)(19)(20)(23)(24)(25). A prospective clinical trial is underway to rigorously evaluate its clinical utility and its potential role in RA patient management (26).…”