Impact of baseline anti-cyclic citrullinated peptide-2 antibody concentration on efficacy outcomes following treatment with subcutaneous abatacept or adalimumab: 2-year results from the AMPLE trial

Abstract

Objectives: To examine whether baseline anti-cyclic citrullinated peptide-2 (CCP2) antibody status and concentration correlated with clinical outcomes in patients treated with abatacept or adalimumab on background methotrexate (MTX) in the 2-year AMPLE (Abatacept versus adaliMumab comParison in bioLogic-naïvE rheumatoid arthritis subjects with background MTX) study.

Methods: In this exploratory analysis, anti-CCP2 antibody concentration was measured at baseline, and antibody-positive patients were divided into equal quartiles, Q1-Q4, representing increasing antibody concentrations. Clinical outcomes analysed by baseline anti-CCP2 status and quartile included change from baseline in disease activity and disability and remission rates.

Results: Baseline characteristics were generally comparable across quartiles and treatment groups. In both treatment groups, anti-CCP2 antibody-negative patients responded less well than antibody-positive patients. At year 2, improvements in disease activity and disability and remission rates were similar across Q1-Q3, but were numerically higher in Q4 in the abatacept group; in contrast, treatment effects were similar across all quartiles in the adalimumab group.

Conclusions: In AMPLE, baseline anti-CCP2 positivity was associated with a better response for abatacept and adalimumab. Patients with the highest baseline anti-CCP2 antibody concentrations had better clinical response with abatacept than patients with lower concentrations, an association that was not observed with adalimumab.

Trial registration number: NCT00929864.

Keywords: Ant-CCP; Autoantibodies; DMARDs (biologic); Rheumatoid Arthritis.

Figure 1

(A) Adjusted mean (SE) change from baseline in Disease Activity Score 28 (C reactive protein; DAS28 (CRP)) by baseline cyclic citrullinated peptide-2 (CCP2)-IgG status and quartile. Estimated mean treatment difference at day 729 for anti-CCP2 quartile (Q)1–Q3 combined vs Q4: subcutaneous (SC) abatacept p=0.003, SC adalimumab p=0.358; for anti-CCP2 negative (Neg) vs Q4: SC abatacept p<0.0001, SC adalimumab p=0.0006. (B) Adjusted mean (SE) change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) by baseline CCP2-IgG status and quartile. Estimated mean treatment difference at day 729 for Q1–Q3 combined vs Q4: SC abatacept p=0.021, SC adalimumab p=0.735; for Neg vs Q4: SC abatacept p=0.002, SC adalimumab p=0.005. Adjusted mean changes from baseline were determined for each time point by analysis of covariance, with treatment and DAS28 (CRP) stratification as factors and baseline values as a covariate. Number of patients in each quartile group: Q1 (28–235)=97; Q2 (236–609)=97; Q3 (613–1046)=97; Q4 (1060–4894)=97; Neg (<25)=120.

Figure 2

Percentage (95% CI) of patients achieving (A) Clinical Disease Activity Index (CDAI) remission rates by baseline cyclic citrullinated peptide-2 (CCP2)-IgG status and quartile. (B) Simplified Disease Activity Index (SDAI) remission rates by baseline CCP2-IgG status and quartile. (C) Disease Activity Score 28 (C reactive protein; DAS28 (CRP)) <2.6 by baseline CCP2-IgG status and quartile. p Values indicate the statistical significance of the estimated mean treatment difference at day 729 for anti-CCP2 quartile (Q)1–Q3 combined vs Q4 and for anti-CCP2 negative (Neg) vs Q4. Asterisks indicate p values ≤0.05. Number of patients in each quartile group: Q1 (28–235)=97; Q2 (236–609)=97; Q3 (613–1046)=97; Q4 (1060–4894)=97; Neg (<25)=120. SC, subcutaneous.