Abatacept Treatment May Slow Atherosclerosis Progression

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Treatment with abatacept was shown to decelerate the progression of atherosclerosis, which could be useful for patients with a high risk of cardiovascular disease, according to a study published in Arthritis Research & Therapy.¹

New treatments, including biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) has been proven to improve the prognosis and quality of life in patients with rheumatoid arthritis (RA). Older patients (aged ≥ 65 years) are at a higher risk of developing infections due to bDMARD use. These patients are also more likely to exhibit comorbidities and be treated with > 1 medications, which can hinder the control of disease activity. However, malignancy, risk of infection, and treatment-related complications linked to specific b/tsDMARDs remain inconclusive.²

“RA is a chronic disease that requires long-term treatment, and there seems to be a large variability across different drugs,” wrote a group of Japanese investigators predominately associated with the Toho University School of Medicine. “Thus, it is vital to attain disease control by considering each patient’s needs and selecting the medication that would lead to the most benefits in terms of joint and cardiovascular outcomes.”

To better understand atherosclerosis among a cohort of patients with RA, investigators evaluated the 3-year efficacy and safety in a population of older and younger patients. Eligible patients had clinically diagnosed RA, had a history of being refractory to treatment with csDMARDs, were bDMARD-naïve, and provided written consent.

The open-label, prospective, observational study stratified patients into 4 groups: patients receiving abatacept among younger (aged 20 — 64 years) and older (aged ≥ 65 years) groups (AY and AO, respectively) and patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) among younger and older groups (CY and CO, respectively).

The primary endpoints were changes from baseline in mean intima-media thickness (IMT) of the common carotid artery, IMT max, and plaque score at week 156. Other endpoints of interest were retention rate, disease activity, and adverse effects.

A total of 216 patients were included in the study, of which 52 were placed in the AY cohort, 73 were placed in the AO cohort, 41 were in the CY cohort, and 50 were in the CO cohort. Among the abatacept groups, patients had a mean age of 51.9 years compared with 52.1 years in the csDMARDs group. Disease activity and physical function were higher in the abatacept group compared with the csDMARDs group. Atherosclerosis parameters were higher among older patients in both cohorts.

Patients in both abatacept groups experienced smaller increases in mean IMT, max IMT, and plaque score compared with both csDMARD cohorts at the end of the study. However, differences between groups were not statistically significant.

Results of the multivariate analysis demonstrated significantly lower increases in plaque score in the abatacept cohort compared with csDMARDs when accounting for disease activity at 156 weeks (P = .0303). Additionally, the proportion of patients with good or good/moderate European League Against Rheumatism (EULAR) response were higher in patients receiving abatacept, with no significant differences observed between the older and younger patients. No significant differences were observed in retention rates among older and younger patients receiving abatacept.

Although serious adverse effects, specifically infection, were more frequent in the abatacept cohort compared with csDMARDs, no significant differences were reported.

Investigators noted the observational study design, relatively small sample size, and limited number of cases as limitations. Generalizability was also limited due to the exclusively Japanese population.

“Abatacept may be useful for patients with high risk for cardiovascular disease, such as older patients,” investigators concluded.

References

1. ^{Yamada Z, Muraoka S, Kawazoe M, et al. Long-term effects of abatacept on atherosclerosis and arthritis in older vs. younger patients with rheumatoid arthritis: 3-year results of a prospective, multicenter, observational study. Arthritis Res Ther. 2024;26(1):87. Published 2024 Apr 17. doi:10.1186/s13075-024-03323-8}
2. ^{Askling J, Fahrbach K, Nordstrom B, Ross S, Schmid CH, Symmons D. Cancer risk with tumor necrosis factor alpha (TNF) inhibitors: meta-analysis of randomized controlled trials of adalimumab, etanercept, and infliximab using patient level data. Pharmacoepidermiol Drug Saf. 2011;20:119–30. https://doi.org/10.1002/pds.2046.}