Abatacept Demonstrates Trend Toward Improved Disease Activity in Early RA

Investigators conducted a post hoc analysis of the AMPLE trial.

Abatacept, compared with adalimumab, demonstrates a trend toward improved disease activity in patients with seropositive, erosive, early rheumatoid arthritis (RA), according to research published in Rheumatology and Therapy.

Researchers conducted an exploratory post hoc analysis of results from the AMPLE study (ClinicalTrials.gov identifier NCT00929864) to evaluate the efficacy of abatacept compared with adalimumab in patients with early RA with poor prognostic factors and patients with poor prognostic factors, regardless of the duration of their disease.

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Participants included in the AMPLE trial had RA according to the 1987 American College of Rheumatology (ACR) classification criteria with active disease for ≤5 years despite treatment with methotrexate, and were biologic naive. Patients randomly received either subcutaneous abatacept 125 mg weekly or subcutaneous adalimumab 40 mg once every 2 weeks; both treatments were in conjunction with weekly methotrexate therapy.

In total, 646 patients received treatment (abatacept n=318, adalimumab n=328). Of these patients, 252 and 245 patients in each group, respectively, completed year 2 of treatment. Investigators found that 38 patients treated with abatacept and 45treated with adalimumab were seropositive for rheumatoid factor and/or anticitrullinated protein antibodies, a ≤6-month disease duration, and >1 erosion on baseline radiographs (cohort 1). The remaining patients (280 and 283 in each group) did not have these poor prognostic factors (cohort 2).

In cohort 1, over 2 years, the adjusted mean improvement in Disease Activity Score in 28 Joints using C-reactive protein (DAS28-CRP) and Health Assessment Questionnaire-Disability Index scores were “numerically greater” for patients treated with abatacept compared with the adalimumab-treated group. No difference was noted in cohort 2 over the same period.

Patients in cohort 1 also demonstrated similar differences between patients treated with abatacept and adalimumab across other efficacy measures, including disease activity via the Clinical and Simplified Disease Activity Indices and ACR20/50/70/90 criteria. Patient-reported outcomes, including pain and fatigue scores, were also different between the 2 treatment groups in cohort 1 but not in cohort 2.

Sensitivity analyses adjusting for baseline body weight were performed, demonstrating that body weight had “minimal impact” on treatment efficacy. Another sensitivity analysis reduced cohort 2 to include only patients with ≤6-month disease duration (cohort 3). Within cohort 3, there were no differences between the treatment groups in terms of patient pain or fatigue, although there was a trend toward a benefit associated with abatacept vs adalimumab in terms of DAS28-CRP.

In addition, no between-group differences were noted in mean change for modified Total Sharp Score or in the proportion of patients without radiographic progression at year 1 or 2. Safety profiles between cohorts and between treatment arms were consistent with the original trial.

Limitations to the study included the exploratory, post hoc nature of the research and the small sample size. Additionally, researchers cite the use of the ACR 1987 criteria to identify patients and potential confounding due to baseline differences in body weight, methotrexate dose, and baseline DAS28-CRP score.

“It is hoped that this [research] will lead to the generation of patient-centric, definable biomarkers that will help to achieve more effective, personalized, rapid, and safe care for a greater number of patients,” the researchers concluded.

Disclosure: This clinical trial was supported by Bristol-Myers Squibb. Please see the original reference for a full list of authors’ disclosures.


Fleischmann R, Weinblatt M, Ahmad H, et al. 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)Rheumatol Ther. 2019;6(4):559-571.