Efficacy of Abatacept and Adalimumab in Patients with Early Rheumatoid Arthritis With Multiple Poor Prognostic Factors: Post Hoc Analysis of a Randomized Controlled Clinical Trial (AMPLE)

Abstract

Introduction: Patients with rheumatoid arthritis (RA) with poor prognostic factors, such as seropositivity for anti-citrullinated protein antibodies and early erosions, may benefit from early intensive treatment. However, information to guide physicians on the best choice of therapy in these patients is limited. The objective of this study was to describe the efficacy of subcutaneous abatacept versus adalimumab over 2 years in patients with seropositive, erosive early RA in the AMPLE study.

Methods: This exploratory post hoc analysis compared clinical, functional and radiographic outcomes in two subsets of patients: patients with early RA (≤ 6 months' disease duration) who were seropositive for rheumatoid factor and/or anti-citrullinated protein antibodies and had > 1 radiographic erosion (Cohort 1); and patients with RA and absence of ≥ 1 of these inclusion criteria (Cohort 2).

Results: Of the 646 randomized patients, Cohort 1 included 38 patients receiving abatacept and 45 receiving adalimumab, and Cohort 2 included 280 patients receiving abatacept and 283 receiving adalimumab. Baseline demographics and disease characteristics were generally similar between treatment groups in both cohorts. Over 2 years, in Cohort 1, the adjusted mean change from baseline in the Disease Activity Score in 28 joints (using C-reactive protein) was numerically greater for abatacept than for adalimumab (mean difference at day 365 was 0.9, 95% confidence interval - 1.47 to - 0.33). Similar patterns of improvement were observed for other disease activity measures and physical function, but not for radiographic outcomes. No treatment-related differences were observed in Cohort 2.

Conclusion: This analysis indicates a trend towards improved disease activity and physical function with abatacept versus adalimumab in patients with seropositive, erosive early RA.

Trial registration: ClinicalTrials.gov NCT00929864.

Funding: Bristol-Myers Squibb.

Keywords: DMARDs (biologic); Disease activity; Early rheumatoid arthritis; Rheumatoid arthritis.

Figures

Fig. 1

Adjusted mean change from baseline in the Disease Activity Score in 28 joints using C-reactive protein [DAS28 (CRP)] (a, b) and Health Assessment Questionnaire-Disability Index (HAQ-DI) (c, d) over 2 years, by patient type. n is the number of patients with both post-baseline and baseline measurements. Panels a and c indicate patients with seropositive, erosive early rheumatoid arthritis (RA) treated with abatacept versus adalimumab, respectively. The adjusted mean change in DAS28 (CRP) from baseline at day 365 was − 2.58 [95% confidence interval (CI) − 2.99 to − 2.17] versus − 1.68 (95% CI − 2.10 to − 1.25) and that in HAQ-DI from baseline at day 365 was − 0.70 (95% CI − 0.90 to − 0.51) versus − 0.50 (95% CI − 0.71 to − 0.30). For calculation of the 95% CI within each group, normal approximation was used if n ≥ 5, otherwise the exact method was used. The dagger symbol indicates that adjustment was based on an analysis of the covariance model with treatment as a factor and baseline values and DAS28 (CRP) stratification as covariates

Fig. 2

Adjusted mean change from baseline in the Clinical Disease Activity Index (CDAI) (a, b) and Simplified Disease Activity Index (SDAI) (c, d) at 1 and 2 years, by patient type (Cohort 1: a, c; Cohort 2: b, d). All randomized and treated patients were included in the analysis; n is the number of patients with both post-baseline and baseline measurements. Asterisk indicates patients with seropositive, erosive early RA treated with abatacept versus adalimumab, respectively. The adjusted mean change from baseline at day 365 was − 25.68 (95% CI − 29.88 to − 21.49) versus − 19.28 (95% CI − 23.55 to − 15.02) for CDAI and − 26.71 (95% CI − 31.09 to − 22.33) versus − 20.22 (95% CI − 24.70 to − 15.74) for SDAI. For calculation of the 95% CI within each group, normal approximation was used if n ≥ 5, otherwise the exact method was used. The dagger indicates that adjustment was based on an analysis of covariance model with treatment as a factor and baseline values and DAS28 (CRP) stratification as covariates

Fig. 3

American College of Rheumatology (ACR) response rate at day 365 in Cohort 1 (a) and Cohort 2 (b). All randomized and treated patients were included in the analysis. In Cohort 1, the mean differences in ACR response rates between treatment arms were: ACR20, 29.0 (95% CI 10.1 to 47.9); ACR50, 18.6 (95% CI − 4.1 to 41.2); ACR70, 13.3 (95% CI − 6.7 to 33.4); ACR90: 5.7 (95% CI − 6.9 to 18.3). Estimates of difference and 95% CIs were based on the minimum risk weights method with randomization stratification of screening DAS28 (CRP). ACR20/50/70/90 ≥ 20/50/70/90% improvement in the ACR response criteria, SC subcutaneous

Fig. 4

Comparison of treatments by remission outcomes and DAS28 (CRP) of a) and Cohort 2 (b). Asterisk denotes that Boolean remission is defined as tender joint count of ≤ 1, swollen joint count of ≤    1, CRP of ≤ 1 mg/dL and patient global assessment   of ≤ 1 (on a 0–10 scale)