Decreased Rates of RA Development
Of these ACPA–negative patients stratified as increased risk, 3 of 35 (9%) in the treatment group developed RA, compared with 9 of 31 (29%) in the placebo arm (hazard ratio [HR], 0.27; P = .034).
All 54 ACPA–positive patients enrolled in the study were classified as either increased risk or high risk, but the treatment showed no difference in the rate of RA development in this group, and more than half (56%) developed RA during 4 years of follow-up. However, Dr. van der Helm-van Mil noted that the 2-year data showed treatment improved the severity of subclinical inflammation and symptoms over time in these patients.
The 5-year data from the trial, including physical function and other measures of disease burden, will be analyzed in 2025, she said, and will reveal whether ACPA–negative patients treated with MTX had sustained improvements in these measures.
Additional studies are needed to validate these findings, Dr. van der Helm-van Mil said, but the results indicate that ACPA–positive and ACPA–negative patients “are different populations, and we should evaluate them separately.”
Future RA prevention studies should also risk stratify patients before enrollment so that patients at low risk of developing the disease are not included in the interventions. “You can’t expect a treatment effect if there is no risk for disease,” she added.
Is It Cost-Effective?
In a separate analysis, published in Annals of the Rheumatic Diseases, Dr. van der Helm-van Mil and colleagues sought to investigate the cost-effectiveness of the TREAT EARLIER intervention at 2 years of follow-up.
“There is an ongoing debate whether people with arthralgia at risk for RA should be treated with DMARDs [disease-modifying antirheumatic drugs]; however, the economic effects of an intervention in the arthralgia at risk phase are unknown.”
The analysis calculated healthcare productivity and work productivity costs from enrollment to 2 years of follow-up. To demonstrate effect, they also calculated change in quality-adjusted life years (QALYs).
Over the course of 2 years, estimated costs for the treatment arm were €4809 lower (−$5304) than the placebo arm per patient. Lower productivity costs accounted for 97% of this difference.
The treatment arm also resulted in a small improvement (+0.041) in QALYs, compared with placebo.
“These data provide the first evidence that first-line treatment aiming at secondary prevention in arthralgia at-risk for RA is cost-effective,” the authors wrote.
Dr. van der Helm-van Mil emphasized that this cost analysis used only 2-year follow-up data (rather than the newly published 4-year data) and did not differentiate ACPA–negative patients. Despite including a greater heterogeneity of patients, the intervention was still cost-effective. A future analysis that includes 5-year follow-up data and stratifies patients by ACPA status and excludes low-risk individuals could demonstrate more cost benefits to a temporary MTX regimen, she said.
Considering the costs of these preventive interventions is important, added Dr. Deane, who agreed that future analyses should examine cost-effectiveness in groups at high risk of developing RA. (Dr. Deane noted that he had reviewed this article for publication.) However, this analysis did not include the costs of screening patients before enrollment in the study.
Richard Mark Kirkner/MDedge News
Dr. Kevin D. Deane
“Additional factors that need to be considered are costs to find individuals who would meet the criteria for treatment,” he said, which would include getting an MRI to detect subclinical joint inflammation.
However, Dr. van der Helm-van Mil noted that both placebo and treatment groups received MRI scans, which would therefore not affect cost differences between the groups.
Future studies should also focus on longer-term outcomes, both Dr. Deane and Dr. van der Helm-van Mil agreed.
“Since RA is a chronic disease for which part of the patients require expensive biologicals, future cost-effectiveness analyses should also consider a lifetime horizon,” Dr. van der Helm-van Mil and colleagues wrote.
The TREAT EARLIER trial was funded by the Dutch Research Council and the Dutch Arthritis Society. The cost analysis study was funded by ZonMw and the Dutch Arthritis Society. Dr. Deane is a member of an American College of Rheumatology/European Alliance of Associations for Rheumatology task force for risk stratification in RA. He has received payments as a speaker for Werfen and Thermo Fisher Scientific and low-cost biomarker assays for research from Werfen. He has also received grant funding from Thermo Fisher Scientific, Gilead, and Boehringer Ingelheim. Dr. van der Helm-van Mil reported no disclosures.
A version of this article first appeared on Medscape.com.