Low Multi-biomarker Disease Activity Scores Research Articles

Uptake and Clinical Utility of Multibiomarker Disease Activity Testing in the United States.

The clinical utility of the multibiomarker disease activity (MBDA) test for rheumatoid arthritis (RA) management in routine care in the United States has not been thoroughly studied. Using 2011-2015 Medicare data, we linked each patient with RA to their MBDA test result. Initiation of a biologic or Janus kinase (JAK) inhibitor in the 6 months following MBDA testing was described. Multivariable adjustment evaluated the likelihood of adding or switching biologic/JAK inhibitor, controlling for potential confounders. For patients with high MBDA scores who added a new RA therapy and were subsequently retested, lack of improvement in the MBDA score was evaluated as a predictor of future RA medication failure, defined by the necessity to change RA medications again. Among 60,596 RA patients with MBDA testing, the proportion adding or switching biologics/JAK inhibitor among those not already taking a biologic/JAK inhibitor was 9.0% (low MBDA), 11.8% (moderate MBDA), and 19.7% (high MBDA, p < 0.0001). Similarly, among those already taking biologics/JAK inhibitor, the proportions were 5.2%, 8.3%, and 13.5% (p < 0.0001). After multivariable adjustment, referent to those with low disease MBDA scores, the likelihood of switching was 1.51-fold greater (95% CI 1.35-1.69) for patients with moderate MBDA scores, and 2.62 (2.26-3.05) for patients with high MBDA scores. Among those with high MBDA scores who subsequently added a biologic/JAK inhibitor and were retested, lack of improvement in the MBDA score category was associated with likelihood of future RA treatment failure (OR 1.61, 95% CI 1.27-2.03). The MBDA score was associated with both biologic and JAK inhibitor medication addition/switching and subsequent treatment outcomes.

A Multi-Biomarker Disease Activity Score and the Choice of Second-Line Therapy in Early Rheumatoid Arthritis After Methotrexate Failure.

ObjectiveTo investigate whether the Multi‐Biomarker Disease Activity (MBDA) score predicts optimal add‐on treatment in patients with early rheumatoid arthritis (RA) who were inadequate responders to MTX (MTX‐IRs).MethodsWe analyzed data from 157 MTX‐IRs (with a Disease Activity Score using the erythrocyte sedimentation rate [DAS28‐ESR] >3.2) from the Swedish Pharmacotherapy (SWEFOT) trial who were randomized to receive triple therapy (MTX plus sulfasalazine plus hydroxychloroquine) versus MTX plus infliximab. The MBDA score as a predictor of the subsequent DAS28‐based response to each second‐line treatment was analyzed at randomization with the Breslow‐Day test for 2 × 2 groups, using both validated categories (low [<30], moderate [30–44], and high [>44]) and dichotomized categories (lower [≤38] versus higher [>38]).ResultsAmong the 157 patients, 12% had a low MBDA score, 32% moderate, and 56% high. Of those with a low MBDA score, 88% responded to subsequent triple therapy, and 18% responded to MTX plus infliximab (P = 0.006); for those with a high MBDA score, the response rates were 35% and 58%, respectively (P = 0.040). When using 38 as a cutoff for the MBDA score (29% patients with lower scores versus 71% with higher scores), the differential associations with response to triple therapy versus MTX plus infliximab were 79% versus 44% and 36% versus 58%, respectively (P = 0.001). Clinical and inflammatory markers had poorer predictive capacity for response to triple therapy or MTX plus infliximab.ConclusionIn patients with RA who had an inadequate response to MTX, the MBDA score categories were differentially associated with response to subsequent therapies. Thus, patients with post‐MTX biochemical improvements (lower MBDA scores) were more likely to respond to triple therapy than to MTX plus infliximab. If confirmed, these results may help to improve treatment in RA.

Association of the multi-biomarker disease activity score with joint destruction in patients with rheumatoid arthritis receiving tumor necrosis factor-alpha inhibitor treatment in clinical practice

Objective: Evaluate the association between the multi-biomarker disease activity (MBDA) score and radiographic progression in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor (TNF)-α inhibitors.Methods: Change (Δ) in modified total Sharp score (mTSS) over 52 weeks and disease activity scores were examined retrospectively by Spearman's rank correlation coefficient in patients (N = 83) with RA initiating TNF-inhibitor treatment. Relative risk (RR) of ΔmTSS >0.5 for low MBDA score and 28-joint count disease activity score (DAS28) categories and associations between ΔmTSS and MBDA score categories conditional on DAS28 categories were assessed.Results: At 52 weeks, 34% of patients had ΔmTSS >0.5 and 12% had ΔmTSS >3. Strongest correlations were observed between ΔmTSS and MBDA score (r = 0.47) or DAS28 (r = 0.42) at Week 24 and for area under the curve at Week 52 (MBDA score: r = 0.44, DAS28: r = 0.41), all p < 0.001. At Week 24, RR of ΔmTSS >0.5 for moderate/high MBDA score (≥30) or DAS28 (>3.2) were 6.6 (p < 0.001) and 2.7 (p = 0.005), respectively. Low DAS28 had greater risk of ΔmTSS >0.5 at 52 weeks when MBDA score was ≥30 (p < 0.05).Conclusion: Higher MBDA score or DAS28 at Week 24 was associated with greater radiographic progression over 52 weeks of TNF-inhibitor treatment. MBDA score improved risk discrimination for radiographic progression within DAS28 categories.

Association of a multibiomarker disease activity score at multiple time-points with radiographic progression in rheumatoid arthritis: results from the SWEFOT trial

ObjectivesIn rheumatoid arthritis (RA), predictive biomarkers for subsequent radiographic progression (RP) could improve therapeutic choices for individual patients. We previously showed that the multibiomarker disease activity (MBDA) score in patients...

Relationship of multi-biomarker disease activity score and other risk factors with radiographic progression in an observational study of patients with rheumatoid arthritis.

Objectives. To evaluate the multi-biomarker disease activity (MBDA) score as a predictor of radiographic progression and compare it with other risk factors among patients with established RA receiving non-biologic DMARDs.Methods. For 163 patients with RA, we assessed 271 visits for MBDA score (scale of 1−100), clinical data and subsequent 1-year radiographic progression (change in Sharp−van der Heijde score [SHS]). Scatter plot and non-parametric quantile regression curves evaluated the relationship between the MBDA score and change in SHS. Changes in joint space narrowing and erosions were compared among MBDA categories with Wilcoxon rank-sum tests. The ability of the MBDA score to independently predict progression was determined by multivariate models and cross-classification of MBDA score with other risk factors. Generalized estimating equation methodology was used in model estimations to adjust for same-patient visits, always ≥1 year apart.Results. Patient characteristics included 67% female, 66%/67% RF+/anti-CCP+; mean age 55 years, MBDA score 43 (moderate = 30−44); median disease duration 4.6 years, SHS 23. Radiographic progression was infrequent for low MBDA scores. Relative risk for progression increased continuously as the MBDA score increased, reaching 17.4 for change in SHS >5 with MBDA scores ≥60. Joint space narrowing and erosion progression were associated with MBDA score. MBDA score was associated with radiographic progression after adjustments for other risk factors. MBDA score significantly differentiated risk for progression when swollen joint count, CRP or DAS28–CRP was low, and among seropositive patients.Conclusion. MBDA score enhanced the ability of conventional risk factors to predict radiographic progression in patients with established RA receiving non-biologic DMARDs.

SAT0045 In Early RA, the Multi-Biomarker Disease Activity Score at Different Time-Points is Predictive of Subsequent Radiographic Progression

BackgroundThe prediction of radiographic progression in early rheumatoid arthritis (eRA) patients is important for optimal treatment. We previously demonstrated that a multi-biomarker disease activity (MBDA) score at baseline (BL) was...

FRI0042 Validation of A Multi-Biomarker Disease Activity Score in Rheumatoid Arthritis in Relation to Imaging Inflammation and Damage

BackgroundA multi-biomarker disease activity (MBDA) score has been validated as a measure of disease activity in rheumatoid arthritis (RA).ObjectivesThis study aimed to further validate the MBDA score in relation to...

THU0254 Residual Inflammatory Activity Assessed by A Multi-Biomarker Disease Activity Blood Test is Linked to Structural Damage in RA Patients in Low Disease Activity/Remission and Normal C-Reactive Protein Level

BackgroundThe autoantibody positive (AAB+) subset of rheumatoid arthritis (RA) patients is prone to develop bone damage. Since the extent of bone erosion in AAB+ RA shows substantial variation, we hypothesized...

SAT0012 A Multi-Biomarker Disease Activity (VECTRA™ DA Algorithm) Score is Associated with Radiographic Outcomes in RA Patients Treated with TNF Inhibitors

BackgroundA novel multi-biomarker disease activity (MBDA) score that is based on the concentrations of 12 serum biomarkers has been shown to correlate with clinical disease activity in patients with rheumatoid...

Quantitative characteristics of the Feyrter (APUD) cells of the neonatal rabbit lung in normoxia and chronic hypoxia.

Our studies show that the apparent number of Feyrter cells in the lung declines during the neonatal period in normoxic rabbits, and that in hypoxic animals a uniformly and significantly lower number of cells occurs as compared with the normoxic rabbits. There is some indication of degranulation of cells in the hypoxic groups. It is suggested that environmental and/or physiological factors associated with the start of extrauterine life, or lung development, may affect the apparent number and probable level of activity of these cells. These changes seem to be enhanced by hypoxia. Mast cells are scarce, and Feyrter cells are relatively more numerous along the airways. These cell types could possibly represent storage sites for 5-hydroxytryptamine, as suggested also by other investigators. Intraepithelial nerve fibres in bronchi and bronchioles were found but they were not limited to innervations of Feyrter cells or related cell bodies.