scholarly journals Adjustment of the multi-biomarker disease activity score to account for age, sex and adiposity in patients with rheumatoid arthritis

Rheumatology ◽  
2018 ◽  
Vol 58 (5) ◽  
pp. 874-883 ◽  
Author(s):  
Jeffrey R Curtis ◽  
Darl D Flake ◽  
Michael E Weinblatt ◽  
Nancy A Shadick ◽  
Mikkel Østergaard ◽  
...  

Abstract Objective To develop and evaluate an adjusted score for the multi-biomarker disease activity (MBDA) test to account for the effects of age, sex and adiposity in patients with RA. Methods Two models were developed to adjust MBDA score for age, sex and adiposity, using either serum leptin concentration or BMI as proxies for adiposity. Two cohorts were studied. A cohort of 325 781 RA patients who had undergone commercial MBDA testing and had data for age, sex and serum leptin concentration was used for both models. A cohort of 1411 patients from five studies/registries with BMI data was used only for the BMI-adjusted MBDA score. Univariate and multivariate linear regression analyses evaluated the adjusted MBDA scores and conventional clinical measures as predictors of radiographic progression, assessed in terms of modified total Sharp score (ΔmTSS). Results Two models were developed, based on findings that MBDA score was higher in females than males and increased with age, leptin concentration and BMI. In pairwise regression analyses, the leptin-adjusted (P = 0.00066) and BMI-adjusted (P = 0.0027) MBDA scores were significant independent predictors of ΔmTSS after adjusting for DAS28-CRP, whereas DAS28-CRP was not, after adjusting for leptin-adjusted (P = 0.74) or BMI-adjusted (P = 0.87) MBDA score. Moreover, the leptin-adjusted MBDA score was a significant predictor of ΔmTSS after adjusting for the BMI-adjusted MBDA score (P = 0.025) or the original MBDA score (0.027), whereas the opposite was not true. Conclusion Leptin-adjusted MBDA score significantly adds information to DAS28-CRP and the original MBDA score in predicting radiographic progression. It may offer improved clinical utility for personalized management of RA.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 954.1-954
Author(s):  
M. Movahedi ◽  
D. Weber ◽  
P. Akhavan ◽  
E. Keystone

Background:Progressive rheumatoid arthritis (RA) is responsible for joint damage causing disabilities with no agreement on which disease measures best predict radiographic progressionObjectives:We aimed to determine which disease activity measures including disease activity score (DAS), modified (M) DAS28 (CRP), clinical disease activity index (CDAI), and health assessment questionnaire disability index (HAQ-DI) best predict rapid radiographic progression (RRP) in early RA patients at baseline (BL) and 3 months.Methods:PREMIER data, a 2-year, multicenter, double-blind active comparator–controlled study with methotrexate (MTX) naïve RA patients and active disease <3 years, were used. Only patients in the MTX arm were analyzed. RRP was defined as change in modified total Sharp (mTSS) > 3.5 at month 12. Logistic regression analysis assessed impact of measures at BL and 3 months on RRP at 12 months. Best cut-off points of M-DAS28(CRP) was also estimated using area under the receiver operating characteristic curve.Results:149 patients were included: female (n=113; 75.8%), positive RF (n=127; 85.2%), mean (SD) age 52.9 (13.3) years, disease duration 0.8 (0.9) year, DAS28(CRP) 6.3 (0.9). After adjusting for potential confounders, only M-DAS28(CRP) at BL (adjOR=3.29; 95% CI: 1.70-6.36) and 3 months (adjOR=2.56; 95% CI: 1.43-4.56) strongly predicted RRP at 12 months. M-DAS28(CRP) 4.5 and 2.6 at BL and 3 months maximized sensitivity and specificity for prediction of RRP.Conclusion:M-DAS28(CRP) was a stronger predictor at BL and 3 months for RRP compared with other disease activity measures. Removing tender joint count and patient global assessment from DAS28(CRP) improves prediction of RRP.References:[1] Breedveld FC, Weisman MH, Kavanaugh AF, Cohen SB, Pavelka K, van Vollenhoven R, et al. The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis and rheumatism. 2006;54(1):26-37.Acknowledgments :The authors wish to knowledge AbbVie Canada Inc. for providing patients data.Disclosure of Interests:Mohammad Movahedi Consultant of: Allergan, Deborah Weber: None declared, Pooneh Akhavan: None declared, Edward Keystone Grant/research support from: AbbVie; Amgen; Gilead Sciences, Inc; Lilly Pharmaceuticals; Merck; Pfizer Pharmaceuticals; PuraPharm; Sanofi, Consultant of: AbbVie; Amgen; AstraZeneca Pharma; Bristol-Myers Squibb Company; Celltrion; F. Hoffman-La Roche Ltd.; Genentech, Inc; Gilead Sciences, Inc.; Janssen, Inc; Lilly Pharmaceuticals; Merck; Myriad Autoimmune; Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, Samsung Bioepsis., Speakers bureau: AbbVie; Amgen; Bristol-Myers Squibb; Celltrion; F. Hoffman-La Roche Ltd, Janssen, Inc; Merck; Pfizer Pharmaceuticals; Sanofi-Genzyme; UCB


2018 ◽  
Vol 77 (10) ◽  
pp. 1421-1425 ◽  
Author(s):  
Nina Paulshus Sundlisæter ◽  
Anna-Birgitte Aga ◽  
Inge Christoffer Olsen ◽  
Hilde Berner Hammer ◽  
Till Uhlig ◽  
...  

ObjectiveTo explore associations between remission, based on clinical and ultrasound definitions, and future good radiographic and physical outcome in early rheumatoid arthritis (RA).MethodsNewly diagnosed patients with RA followed a treat-to-target strategy incorporating ultrasound information in the Aiming for Remission in rheumatoid arthritis: a randomised trial examining the benefit of ultrasound in a Clinical TIght Control regimen (ARCTIC) trial. We defined 6-month remission according to Disease Activity Score, Disease Activity Score in 28 joints-erythrocyte sedimentation rate, American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean criteria, Simplified Disease Activity Index, Clinical Disease Activity Index and two ultrasound definitions (no power Doppler signal, grey scale score ≤2). Two outcomes were defined: no radiographic progression and good outcome (no radiographic progression+physical function≥general population median), both sustained 12–24 months. We calculated the ORs of these outcomes for the remission definitions.ResultsOf 103 patients, 42%–82% reached remission at 6 months, dependent on definition. Seventy-one per cent of patients had no radiographic progression and 37% had good outcome. An association between 6-month remission and no radiographic progression was observed for ACR/EULAR Boolean remission (44 joints, OR 3.2, 95% CI 1.2 to 8.4), ultrasound power Doppler (OR 3.6, 95% CI 1.3 to 10.0) and grey scale remission (OR 3.2, 95% CI 1.2 to 8.0). All clinical, but not ultrasound remission criteria were associated with achievement of a good outcome.ConclusionsOur data support ACR/EULAR Boolean remission based on 44 joints as the preferred treatment target in early RA. Absence of ultrasound inflammation was associated with no radiographic progression.Trial registration numberNCT01205854; Post-results.


2013 ◽  
Vol 73 (3) ◽  
pp. 536-543 ◽  
Author(s):  
Tsutomu Takeuchi ◽  
Hisashi Yamanaka ◽  
Naoki Ishiguro ◽  
Nobuyuki Miyasaka ◽  
Masaya Mukai ◽  
...  

ObjectivesTo evaluate the efficacy and safety of adalimumab+methotrexate (MTX) in Japanese patients with early rheumatoid arthritis (RA) who had not previously received MTX or biologics.MethodsThis randomised, double-blind, placebo-controlled, multicentre study evaluated adalimumab 40 mg every other week+MTX 6–8 mg every week versus MTX 6–8 mg every week alone for 26 weeks in patients with RA (≤2-year duration). The primary endpoint was inhibition of radiographic progression (change (Δ) from baseline in modified total Sharp score (mTSS)) at week 26.ResultsA total of 171 patients received adalimumab+MTX (mean dose, 6.2±0.8 mg/week) and 163 patients received MTX alone (mean dose, 6.6±0.6 mg/week, p<0.001). The mean RA duration was 0.3 years and 315 (94.3%) had high disease activity (DAS28>5.1). Adalimumab+MTX significantly inhibited radiographic progression at week 26 versus MTX alone (ΔmTSS, 1.5±6.1 vs 2.4±3.2, respectively; p<0.001). Significantly more patients in the adalimumab+MTX group (62.0%) did not show radiographic progression (ΔmTSS≤0.5) versus the MTX alone group (35.4%; p<0.001). Patients treated with adalimumab+MTX were significantly more likely to achieve American College of Rheumatology responses and achieve clinical remission, using various definitions, at 26 weeks versus MTX alone. Combination therapy was well tolerated, and no new safety signals were observed.ConclusionsAdalimumab in combination with low-dose MTX was well tolerated and efficacious in suppressing radiographic progression and improving clinical outcomes in Japanese patients with early RA and high disease activity.


2015 ◽  
Vol 8 ◽  
pp. CMAMD.S22155 ◽  
Author(s):  
Katsuaki Kanbe ◽  
Junji Chiba ◽  
Yasuo Inoue ◽  
Masashi Taguchi ◽  
Akiko Yabuki

In order to investigate the predictive factors related to clinical efficacy and radiographic progression at 24 weeks by looking at the serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 including baseline characteristics in patients with rheumatoid arthritis (RA) treated with golimumab, serum concentrations of TNF-α and IL-6 were analyzed every 4 weeks up to 24 weeks in 47 patients treated with golimumab. Baseline levels of the Disease Activity Score 28 C-reactive protein (DAS28-CRP) and Simplified Disease Activity Index (SDAI) scores were also assessed. Radiographic progression using the van der Heijde-modified Sharp (vdH-S) score was assessed in 29 patients. Multiple regression analyses related to the DAS28-CRP score and delta total sharp score at 24 weeks was undertaken using the baseline characteristics of patients and serum concentrations of matrix metalloproteinase (MMP)-3, TNF-α, and IL–6. The DAS28-CRP score and SDAI decreased significantly at 4 weeks up to 24 weeks compared with baseline. Serum levels of TNF-α were not changed significantly up to 24 weeks compared with baseline, but those of IL-6 decreased significantly at 4 weeks up to 8 weeks. Multiple regression analyses showed that disease duration and serum levels of MMP-3 were related significantly to the DAS28-CRP score at 24 weeks. Radiographic progression was related significantly to disease duration with regard to joint space narrowing and bone erosion. However, serum levels of TNF-α and IL-6 were not correlated significantly with the DAS28-CRP score and radiographic progression. These data suggest that decreasing serum levels of IL-6 significantly, MMP-3, and disease duration are predictive factors for RA activity in patients taking golimumab.


2014 ◽  
Vol 41 (11) ◽  
pp. 2114-2119 ◽  
Author(s):  
Iris M. Markusse ◽  
Linda Dirven ◽  
Marianne van den Broek ◽  
Casper Bijkerk ◽  
K. Huub Han ◽  
...  

Objective.To determine whether a multibiomarker disease activity (MBDA) score predicts radiographic damage progression in the subsequent year in patients with early rheumatoid arthritis.Methods.There were 180 serum samples available in the BeSt study (trial numbers NTR262, NTR 265): 91 at baseline (84 with radiographs available) and 89 at 1-year followup (81 with radiographs available). Radiographs were assessed using the Sharp/van der Heijde Score (SvdH). Twelve serum biomarkers were measured to determine MBDA scores using a validated algorithm. Receiver-operating curves and Poisson regression analyses were performed, with Disease Activity Score (DAS) and MBDA score as independent variables, and radiographic progression as dependent variable.Results.At baseline, MBDA scores discriminated more between patients who developed radiographic progression (increase in SvdH ≥ 5 points) and patients who did not [area under the curve (AUC) 0.767, 95% CI 0.639–0.896] than did DAS (AUC 0.521, 95% CI 0.358–0.684). At 1 year, MBDA score had an AUC of 0.691 (95% CI 0.453–0.929) and DAS had an AUC of 0.649 (95% CI 0.417–0.880). Adjusted for anticitrullinated protein antibody status and DAS, higher MBDA scores were associated with an increased risk for SvdH progression [relative risk (RR) 1.039, 95% CI 1.018–1.059 for baseline MBDA score; 1.037, 95% CI 1.009–1.065 for Year 1 MBDA score]. Categorized high MBDA scores were also correlated with SvdH progression (RR for high MBDA score at baseline 3.7; low or moderate MBDA score as reference). At 1 year, high MBDA score gave a RR of 4.6 compared to low MBDA score.Conclusion.MBDA scores predict radiographic damage progression at baseline and during disease course.


RMD Open ◽  
2016 ◽  
Vol 2 (1) ◽  
pp. e000197 ◽  
Author(s):  
Karen Hambardzumyan ◽  
Rebecca J Bolce ◽  
Saedis Saevarsdottir ◽  
Kristina Forslind ◽  
Johan K Wallman ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document