Brief Report: Estimating Disease Activity Using Multi-Biomarker Disease Activity Scores in Rheumatoid Arthritis Patients Treated With Abatacept or Adalimumab

Abstract

Objective: To assess the ability of a multi-biomarker disease activity (MBDA) test (Vectra DA) to reflect clinical measures of disease activity in patients enrolled in the AMPLE (Abatacept Versus Adalimumab Comparison in Biologic-Naive RA Subjects with Background Methotrexate) trial.

Methods: In the AMPLE trial, patients with active rheumatoid arthritis (RA) who were naive to biologic agents and had an inadequate response to methotrexate were randomized (1:1) to receive subcutaneous abatacept (125 mg every week) or subcutaneous adalimumab (40 mg every 2 weeks), with background methotrexate, for 2 years. The MBDA score was determined using serum samples collected at baseline, month 3, and years 1 and 2. The adjusted mean change from baseline in the MBDA score was compared between the abatacept and adalimumab treatment groups. Cross-tabulation was used to compare the MBDA score with the following clinical measures of disease activity: Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP), and Routine Assessment of Patient Index Data 3 (RAPID-3).

Results: In total, 318 patients were randomized to receive abatacept, and 328 were randomized to receive adalimumab; MBDA data were available for 259 and 265 patients, respectively. No association between the MBDA score and disease activity defined by the CDAI, SDAI, DAS28-CRP, or RAPID-3 in the abatacept and adalimumab treatment groups was observed.

Conclusion: The MBDA score did not reflect clinical disease activity in patients enrolled in AMPLE and should not be used to guide decision-making in the management of RA, particularly for patients who receive abatacept or adalimumab as the first biologic agent.

Trial registration: ClinicalTrials.gov NCT00929864.

Figure 1

Adjusted mean changes from baseline over time in the multi‐biomarker disease activity (MBDA) score (A) and the Disease Activity Score in 28 joints using the C‐reactive protein value (B) for all randomized and treated patients for whom an MBDA score was available. The last observation carried forward approach was used. Horizontal bars show the 95% confidence interval. SC = subcutaneous.

Figure 2

A and B, Comparison of clinical measures of disease activity and MBDA score categories, for the Disease Activity Score in 28 joints using the C‐reactive protein level (DAS28‐CRP) (A) and the Clinical Disease Activity Index (CDAI) (B), at baseline and year 2. C and D, Comparison of disease activity as assessed using the CDAI (C) and the MBDA score (D) in patients with radiographic nonprogression, at years 1 and 2. For the CDAI, remission was defined as a score of ≤2.8, low disease activity (LDA) as a score of >2.8 to ≤10, moderate disease activity (MDA) as a score of >10 to ≤22, and high disease activity (HDA) as a score of >22. For MBDA, LDA was defined as a score of <30, MDA as a score of 30–44, and HDA as a score of >44. Radiographic nonprogression was defined as change from baseline in the total score less than or equal to the smallest detectable change. See Figure 1 for other definitions.