Heart Risks Elevated in RA Patients Despite Biologic Tx Save

Hopes that biologic drugs for rheumatoid arthritis (RA) would cancel the extra cardiovascular risks normally seen with the disease dimmed a little in the face of findings from a population-based study from Scandinavia.

Over the first 5 years after beginning biologic agents such as tumor necrosis factor (TNF) and interleukin (IL) inhibitors, RA patients in Denmark developed acute coronary syndrome (ACS) at a rate of 4.5 per 1,000 person-years, compared with 2.4 per 1,000 person-years among the general population, for a hazard ratio of 1.8 (95% CI 1.5-2.1), according to Bénédicte Delcoigne, MSc, PhD, of Karolinska Institutet in Stockholm, and colleagues.

Data from Sweden were similar, with ACS incidence rates of 6.6 and 3.6 per 1,000 person-years for RA patients and the general public, respectively, again for a hazard ratio of 1.8 (95% CI 1.6-2.0), the group reported in Annals of the Rheumatic Diseases.

These elevations in risk for ACS were apparent at shorter follow-up periods as well. But they did not differ markedly among different types of biologic agents, which spanned TNF inhibitors such as infliximab (Remicade), adalimumab (Humira), and etanercept (Enbrel); the IL-6 inhibitor tocilizumab (Actemra); the anti-B cell agent rituximab (Rituxan); and the T-cell inhibitor abatacept (Orencia).

There were some exceptions: patients on abatacept, rituximab, or infliximab did show significantly greater ACS rates than those using etanercept in some analyses. But Delcoigne and colleagues suggested this might not necessarily reflect drug effects, but rather "might be explained by residual confounding or confounding by indication."

For example, "[p]atients on abatacept and rituximab had more comorbidities and longer disease duration with potentially longer exposure to inflammation, which is associated with CV [cardiovascular] risk," the researchers suggested.

These results stand somewhat in contrast to previous studies that showed reduced risk of cardiovascular events with biologic drugs. But those studies had typically compared patients on these agents to historical controls or to patients receiving nonbiologic drugs or placebo.

Epidemiologic data "suggest that a gap in CV risk remains" between biologic-treated RA patients and the general population even as absolute rates have declined for both groups, Delcoigne and colleagues explained. Also, data on such risks for periods longer than 2 years are "sparse," they noted.

To fill these gaps, they drew on national registry data covering 2008-2017 in the countries of Denmark, Norway, Sweden, and Finland, for a total of 24,083 RA patients who started on some type of biologic therapy. Only Denmark and Sweden had available data on ACS events in their general populations that allowed matching patients for age, sex, and residence (at ratios of 10:1 for Denmark and 5:1 for Sweden). ACS was recorded via ICD-10 codes indicating hospitalization for unstable angina or myocardial infarction.

Because of this reliance on registry data, the study came with numerous limitations, including a lack of information on important socioeconomic factors, use of over-the-counter medications or newer prescription drugs such as JAK inhibitors, and varying definitions of ACS among countries. The focus on ACS, excluding other cardiovascular events such as stroke, was also a limitation.

Source Reference: Delcoigne B, et al "Short-term, intermediate-term and long-term risks of acute coronary syndrome in cohorts of patients with RA starting biologic DMARDs: results from four Nordic countries" Ann Rheum Dis 2022; DOI: 10.1136/annrheumdis-2021-221996.