Disease activity measures at baseline predict structural damage progression: data from the randomized, controlled AMPLE and AVERT trials

Edward C Keystone, Harris A Ahmad, Yusuf Yazici, Martin J Bergman, Edward C Keystone, Harris A Ahmad, Yusuf Yazici, Martin J Bergman

Abstract

Objective: Data from two double-blind, randomized, Phase III studies were analysed to investigate the ability of Routine Assessment of Patient Index Data 3, DAS28 (CRP), modified (M)-DAS28 (CRP) and Simplified or Clinical Disease Activity Indices to predict structural damage progression in RA.

Methods: This post hoc analysis included data from the 2-year Abatacept vs adaliMumab comParison in bioLogic-naïvE RA subjects with background MTX (AMPLE) trial in biologic-naïve patients with active RA (<5 years) and an inadequate response to MTX, and the 12-month treatment period of the Assessing Very Early Rheumatoid arthritis Treatment (AVERT) trial in MTX-naïve patients with early RA (⩽2 years) and poor prognostic indicators. Adjusted logistic regression analysis assessed the relationship between baseline disease activity and structural damage progression (defined as change from baseline greater than the smallest detectable change) at 12 and 24 months in AMPLE and 6 and 12 months in AVERT. Areas under the receiver operating characteristic curves for the impact of baseline disease activity on structural damage progression were calculated.

Results: Adjusted logistic regression analyses included all randomized and treated patients in AMPLE (N = 646) and those who received abatacept plus MTX or MTX monotherapy in AVERT (N = 235). Baseline Routine Assessment of Patient Index Data 3, DAS28 (CRP) and M-DAS28 (CRP) scores significantly predicted structural progression at months 12 and 24 in AMPLE (P < 0.05) and months 6 and 12 in AVERT (P < 0.01), and were stronger predictors than Simplified or Clinical Disease Activity Indices.

Conclusion: In this post hoc analysis of two patient populations with RA, Routine Assessment of Patient Index Data 3, DAS28 (CRP) and M-DAS28 (CRP) were good at predicting structural damage.

Trial registration: ClinicalTrials.gov, https://ichgcp.net/clinical-trials-registry/NCT00929864" title="See in ClinicalTrials.gov">NCT00929864 (AMPLE); NCT01142726 (AVERT).

Keywords: CDAI; DAS28 (CRP); DMARDs; M-DAS28 (CRP); RA; RAPID3; SDAI; clinical trial; composite indices; disease activity.

© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Figures

Fig . 1
Fig. 1
Cumulative probability of change in (A) mTSS (AMPLE) and (B) MRI erosion score (AVERT) The analysis includes pooled data for all randomized and treated patients in each study (ITT population); for the AVERT trial, only the abatacept plus MTX and MTX monotherapy arms were included in the analysis. AMPLE: Abatacept vs adaliMumab comParison in bioLogic-naïvE RA subjects with background MTX; AVERT: Assessing Very Early Rheumatoid arthritis Treatment; ITT: intent-to-treat; mTSS: modified total Sharp score.
Fig . 2
Fig. 2
Relationship between baseline disease activity and radiographic progression at months 12 and 24 (AMPLE) The adjusted logistic regression model included pooled data for all randomized and treated patients (ITT population). Odds ratios were adjusted for the following factors: treatment (abatacept vs adalimumab), baseline radiographic total score, sex (male vs female), age (in 5-year increments), weight (in 10-kg increments) and RA duration (per year). Radiographic progression was defined as change from baseline in mTSS greater than the smallest detectable change, which is calculated as s.d./[square root (2) × 1.96], where s.d. is that of the paired differences of change from baseline in total score between two readers. *P < 0.05; †P < 0.01; ‡P < 0.001. AMPLE: Abatacept vs adaliMumab comParison in bioLogic-naïvE RA subjects with background MTX; CDAI: Clinical Disease Activity Index; ITT: intent-to-treat; M-DAS28 (CRP): modified DAS28 (CRP); mTSS: modified total Sharp score; RAPID3: Routine Assessment of Patient Index Data 3; SDAI: Simplified Disease Activity Index.
Fig . 3
Fig. 3
Relationship between baseline disease activity and MRI erosion progression at months 6 and 12 (AVERT) The adjusted logistic regression model included pooled data for all randomized and treated patients (ITT population); only data for the abatacept plus MTX and MTX monotherapy arms were included in the analysis. Odds ratios were adjusted for the following factors: treatment (abatacept + MTX and abatacept alone vs MTX), baseline MRI erosion score, prior corticosteroid use (yes vs no), sex (male vs female), age (in 5-year increments), weight (in 10-kg increments) and RA duration (per year). MRI erosion progression was defined as change from baseline greater than the smallest detectable change, calculated as s.d./[square root (2) × 1.96], where s.d. is that of the paired differences of change from baseline in total score between two readers. *P < 0.01; †P < 0.001. AVERT: Assessing Very Early Rheumatoid arthritis Treatment; CDAI: Clinical Disease Activity Index; ITT: intent-to-treat; M-DAS28 (CRP): modified DAS28 (CRP); RAPID3: Routine Assessment of Patient Index Data 3; SDAI: Simplified Disease Activity Index.
Fig . 4
Fig. 4
ROC curves: baseline disease activity vs radiographic progression at (A) 12 and (B) 24 months (AMPLE) The analysis includes pooled data for all randomized, treated patients from the AMPLE ITT population without missing data for 1- and 2-year radiographic progression for all baseline disease activity measures (n = 578 at 1 year and n = 506 at 2 years). AMPLE: Abatacept vs adaliMumab comParison in bioLogic-naïvE RA subjects with background MTX; AUC: area under the curve; CDAI: Clinical Disease Activity Index; ITT: intent-to-treat; M-DAS28 (CRP): modified DAS28 (CRP); RAPID3: Routine Assessment of Patient Index Data 3; ROC: received operating characteristic; SDAI: Simplified Disease Activity Index.
Fig . 5
Fig. 5
ROC curves: baseline disease activity vs MRI progression at (A) 6 and (B) 12 months (AVERT) The analysis includes pooled data for all randomized, treated patients (abatacept plus MTX and MTX monotherapy arms only) from the AVERT ITT population without missing scores for 6-month or 1-year MRI erosion progression for all baseline disease activity measures [n = 215 for M-DAS28 (CRP) and n = 217 for all other measures at 6 months, and n = 183 for all measures at 2 years]. aM-DAS28 (CRP) 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 this model, the AUC for DAS28 (CRP) and RAPID3 at month 6 were 0.6281 and 0.7157, respectively. AUC: area under the curve; AVERT: Assessing Very Early Rheumatoid arthritis Treatment; CDAI: Clinical Disease Activity Index; ITT: intent-to-treat; M-DAS28 (CRP): modified DAS28 (CRP); RAPID3: Routine Assessment of Patient Index Data 3; ROC: received operating characteristic; SDAI: Simplified Disease Activity Index.

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Source: PubMed

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