Structural Damage in Patients with Very Early RA Is Predicted with Clinical Measures of Baseline Disease Activity: DAS28 (CRP), SDAI, M-DAS28 and RAPID3 but Not CDAI

Edward C. Keystone¹, H Ahmad², Yusuf Yazici³, X Liu² and MJ Bergman⁴, ¹University of Toronto, Toronto, ON, Canada, ²Bristol-Myers Squibb, Princeton, NJ, ³New York University School of Medicine, New York, NY, ⁴Drexel University College of Medicine, Philadelphia, PA

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Abatacept, Disease Activity, joint damage and rheumatoid arthritis (RA), MRI

Session Information

Date: Wednesday, November 8, 2017

Title: Rheumatoid Arthritis – Small Molecules, Biologics and Gene Therapy V: Imaging and Cardiovascular Outcomes Therapy

Session Type: ACR Concurrent Abstract Session

Session Time: 11:00AM-12:30PM

Background/Purpose: Clinicians rely on time-efficient, validated disease activity assessments to help accurately predict disease progression in patients with RA. The utility of the Routine Assessment of Patient Index Data 3 (RAPID3)¹ in predicting structural damage progression is largely unknown, while that of DAS28 (CRP)² and modified (M-)DAS28 have been previously reported.³This post hoc analysis using data from the AVERT (NCT01142726) study investigated the value of baseline clinical measures for predicting structural damage progression with MRI as a measure of progression. Methods: AVERT was a 24-month, active-controlled trial with a 12-month, double-blind treatment period, during which MTX-naïve, ACPA-positive patients with early active RA were randomized (1:1:1) to abatacept 125 mg weekly plus MTX or abatacept or MTX monotherapy, followed by a 12-month withdrawal period, during which all treatment was stopped.⁴Logistic regression analysis, corrected for age, sex and corticosteroid use at baseline, was used to assess the correlation between baseline measures of disease activity (DAS28 [CRP], SDAI, CDAI, M-DAS28 and RAPID3) and the degree of structural joint damage, as assessed by MRI at 6 and 12 months. MRI erosion progression was defined as change from baseline greater than the smallest detectable change, which was calculated as SD/square root (2) x 1.96 (where SD is standard deviation of paired differences of change from baseline in total score between two readers). Results: Logistic regression analysis was carried out for all randomized and treated patients who received abatacept + MTX (n=119) or MTX monotherapy (n=116). For these patients, DAS28 (CRP), M-DAS28 and RAPID3 at baseline were significant predictors of radiographic progression at Months 6 and 12 (Figure). Baseline SDAI was a significant predictor at Month 12 but not Month 6, and baseline CDAI was not a significant predictor at either time point (Figure). At Months 6 and 12, receiver operating characteristic curves showed that RAPID3 had the highest predictive value (area under the curve) for MRI progression (Table).

Conclusion: In this post hoc analysis of MTX-naïve, ACPA-positive patients with early RA, DAS28 (CRP), M-DAS28 and RAPID3 were significant predictors of structural damage progression at Months 6 and 12, as measured using MRI, with RAPID3 showing the highest predictive value for MRI progression. 1. Yazici Y, et al. J Rheumatol 2008;35:603–9. 2. Salaffi F, et al. BMC Musculoskelet Disord 2011;12:120. 3. Baker JF, et al. Arthritis Rheumatol 2014;66:794–802. 4. Emery P, et al. Ann Rheum Dis 2015;74:19–26.

Table. Area Under ROC Curves for the Impact of Disease Activity at Baseline on MRI Progression at Months 6 and 12 (all Randomized and Treated Patients)
Disease activity measure*	AUC at Month 6	AUC at Month 12
DAS28 (CRP)	0.6322	0.6466
RAPID3	0.7181	0.7047
M-DAS28	0.6488	0.6823
CDAI	0.5666	0.5958
SDAI	0.6549	0.6647
*M-DAS28 was calculated based on a different statistical model (which also included DAS28 [CRP] and RAPID3) due to a different number of patients with non-missing values. In the other model, the AUC for DAS28(CRP) and RAPID3 at Month 6 were 0.6281 and 0.7157, respectively. At Month 12 the values were the same for both models AUC=area under the curve; M-DAS28=modified DAS28; ROC=receiver operating characteristic

Disclosure: E. C. Keystone, Abbott Laboratories, Amgen Inc., AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb, F. Hoffmann-La Roche Inc, Janssen Inc, Lilly Pharmaceuticals, Novartis Pharmaceuticals, Pfizer Pharmaceuticals, Sanofi-Aventis, UCB, 2,Abbott Laboratories, AstraZeneca Pharma, Biotest, Bristol-Myers Squibb Company, Crescendo Bioscience, F. Hoffmann-La Roche Inc, Genentech Inc, Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, UCB, 5,Amgen, Abbott Laboratories, Astrazeneca LP, Bristol-Myers Squibb Canada, F. Hoffmann-La Roche Inc., Janssen Inc., Pfizer Pharmaceuticals, Sanofi Genzyme UCB, 8; H. Ahmad, Bristol-Myers Squibb, 3,Bristol-Myers Squibb, 1, 9; Y. Yazici, Genentech, Celgene, BMS, 2,Celgene, 5; X. Liu, Bristol-Myers Squibb, 3; M. Bergman, Pfizer, JNJ, 1,Norvatis, AbbVie, Celgene, 8,AbbVie, BMS, Amgen, Celgene, Genentech, Pfizer, Janssen, GSK Horizon, 5.

To cite this abstract in AMA style:

Keystone EC, Ahmad H, Yazici Y, Liu X, Bergman M. Structural Damage in Patients with Very Early RA Is Predicted with Clinical Measures of Baseline Disease Activity: DAS28 (CRP), SDAI, M-DAS28 and RAPID3 but Not CDAI [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/structural-damage-in-patients-with-very-early-ra-is-predicted-with-clinical-measures-of-baseline-disease-activity-das28-crp-sdai-m-das28-and-rapid3-but-not-cdai/. Accessed .

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