Researchers have found that in biologic-naïve patients with active rheumatoid arthritis (RA), treatment with either subcutaneous abatacept or adalimumab, plus background methotrexate (MTX), resulted in comparable improvements in patient-reported outcomes (PROs), which highly correlated with physician-reported clinical response end points. The results are published in Arthritis Care & Research.
“The treat-to-target strategies employed in RA aim to achieve significant improvements in clinical outcomes, with the goal of remission, or if remission cannot be achieved, low disease activity,” wrote Roy Fleischmann, MD, from the University of Texas Southwestern Medical Center, Dallas, and colleagues. “However, whether achievement of these goals is associated with meaningful improvements in PROs remains unclear”.
High Yield Data Summary
- Comparable improvements in patient-reported outcomes (pain, fatigue, ability to work, and performance of activities of daily living) were noted with abatacept and adalimumab treatment in biologic-naïve patients with active RA
- PRO Improvements correlated with physician-reported end points, including low disease activity or remission
Ideally, PROs should be evaluated in tandem with clinical outcomes. This is even more important when disease activity is assessed without patient-reported components. Both PROs and outcomes, as measured by certain scales of disease activity, are important, thus their relationships warrant further research.
The phase 3 trial Abatacept versus Adalimumab Comparison in Biologic-Naive RA Subjects with Background MTX (AMPLE, ClinicalTrials.gov Identifier NCT00929864) was the first head-to head trial comparing biologic disease-modifying antirheumatic drugs (DMARDs) in patients with RA receiving MTX. The stated purpose of this trial was to evaluate the non-inferiority of subcutaneous abatacept to subcutaneous adalimumab in biologic-naïve patients.
Eligible patients included adults with moderate-to-severe RA as defined by the American College of Rheumatology criteria, who had a history of MTX failure who were naive to RA biologics, and ≤5 years disease duration.
A total of 646 patients were randomized and treated, with 318 patients in the subcutaneous (SC) abatacept group, and 328 patients in the adalimumab group.
Demographic and baseline clinical characteristics, including PRO measures, were well balanced between the 2 treatment groups. Overall, 79.2% of patients treated with SC abatacept and 74.7% of patients treated with adalimumab completed the 2-year study.
Over the 2-year study evaluation period, both treatment groups achieved comparable improvements in PROs, with both achieving clinically meaningful improvements in PROs from baseline. Mean (± SEM) improvements in pain at year 2 for treatment with abatacept vs adalimumab were 53.7% ± 6.2% vs 38.5% ±6.1%, respectively, with an adjusted mean treatment difference of 15.2% (95% CI −1.2, 31.6).
At year 2, fatigue improved by 23.4 mm with abatacept and 21.5 mm with adalimumab on a 100 mm visual analog scale. Clinical responders achieved greater improvements in PROs than nonresponders.
Working impairment was also reduced in both abatacept and the adalimumab groups, with noted overall reduction in work impairment and activity at all postbaseline assessments (month 6, year 1, year 2). Minimum clinically important difference (MCID) for ability to perform daily activities of 4 additional days was also noted in both treatment groups at all those times of subsequent assessment.
Summary & Clinical Applicability
This study demonstrated that in patients with RA who were biologic-naïve, treatment with SC abatacept or adalimumab is associated with comparable improvements in PROs that are considered particularly important, including pain, fatigue, work productivity, and activity limitation. The improved PROs were also associated with physician-reported clinical responses.
“By correlating clinical response with PROs that are important to both physicians and patients, such as pain, fatigue, work productivity, and activity impairment, the achievement of how a good clinical response translates into meaningful benefits for the patient in their daily life can be better understood,” the researchers noted.
Limitations & Disclosures
Although the AMPLE trial was structured to compare abatacept and adalimumab directly, it was single-blind, rather than double-blind design, may have introduced bias.
An additional limitation is the post hoc nature of the analyses comparing PROs in patient subgroups based on clinical response.
Multiple study authors disclose receiving grants, honoraria, consulting fees, or speaking fees from the pharmaceutical industry, including Bristol-Myers Squibb, the manufacturer of abatacept (Orencia©)
Bristol-Myers Squibb funded the NCT00929864 clinical trial
Fleischmann R, Weinblatt ME, Schiff M, et al. Patient-Reported Outcomes From a Two-Year Head-to-Head Comparison of Subcutaneous Abatacept and Adalimumab for Rheumatoid Arthritis. Arthritis Care Res. 2016 Jul;68(7):907-13. doi:10.1002/acr.22763.