Tumor necrosis factor (TNF) inhibitor treatment of rheumatoid arthritis (RA) that successfully reduces RA disease activity also appears to improve cardiovascular (CV) risk in this population.
Compared with European League Against Rheumatism (EULAR) nonresponse to TNF inhibitor therapy, EULAR good response was associated with a 50% lower risk of acute coronary syndrome (ACS). The short-term risk among good responders was "similar to the risk of ACS in the general population," according to Lotta Ljung, MD, PhD, of the Karolinska Institute in Stockholm, and colleagues.
Previous studies have shown that TNF inhibition can help lower the elevated cardiovascular risk among patients with RA, but it has not been determined whether the decreased risk is seen in all patients or only among those responding adequately to therapy.
"The aim of this study was therefore to investigate the effect of response to TNF inhibitor therapy on the short-term risk of ACS in a contemporary cohort of patients with RA," Ljung and colleagues explained in a report online in Annals of the Rheumatic Diseases.
They identified 6,864 RA patients in the Swedish Biologics Register with no history of heart disease starting a first TNF inhibitor during the years 2001 to 2012, and 34,229 healthy controls from the Swedish Population Register.
Response to TNF inhibitor therapy was defined according to EULAR response criteria, which assesses treatment effects over time according to the Disease Activity Score in 28 joints (DAS28) as none, moderate, or good.
The time window for evaluation of response was 2 to 8 months after the start of the treatment. Three definitions of response were used: the first DAS28 score, the best DAS28 in the evaluation time window, and the DAS28 closest to 5 months, which most closely reflects clinical practice.
The mean age of the cohort was 55 years, 77% were women, and 73% had seropositive RA. The most common TNF inhibitors were infliximab (Remicade), in 38%; etanercept (Enbrel), in 36%; and adalimumab (Humira), in 22%.
At the 5-month evaluation, 39% of the patients had a EULAR good response, 34% had a moderate response, and 27% were nonresponders, using the DAS28 closest to 5 months. These percentages were similar when using the first DAS28 and the best DAS28 to define response.
Follow-up started at the time point for evaluation of therapy response and ended at death, emigration, the end of 2012 or when a first ACS occurred, and was limited to 1 year and 2 years, respectively, following response evaluation.
During 6,592 person-years of follow-up in the first year, starting at the visit closest to 5 months, 47 ACS events were recorded, for a crude incidence rate of 7.1 events per 1,000 person-years. With a second year of follow-up, there were 84 ACS events during 12,571 person-years, for a crude incidence rate of 6.7 per 1,000 person-years. The other two response definitions resulted in similar incidence rates.
The ACS incidence rate was lowest among the good response group, ranging from 2.8 to 3.5 per 1,000 person-years at 1 year and from 4.3 to 4.4 per 1,000 person-years at 2 years. The crude incidence rate among moderate and nonresponders ranged from 8.6 to 10 per 1,000 person-years at 1 year and from 7.7 to 9.2 per 1,000 person-years at 2 years.
The adjusted hazard ratios for the 1-year risk of ACS among EULAR good responders compared with nonresponders were 0.5 (95% CI 0.2-1.4), 0.4 (95% CI 0.2-0.9), and 0.5 (95% CI 0.2-1.2) for the first, best, and closest-to-5-months evaluations, respectively.
The adjusted hazard ratios for good responders at 2-year follow-up were similar, at 0.7 (95% CI 0.4-1.3), 0.6 (95% CI 0.4-1.2), and 0.7 (95% CI 0.4-1.2), respectively, for the three evaluation methods.
Good EULAR responders had a fully adjusted risk of ACS that was not significantly different from the general population (HR 1.2, 95% CI 0.6-2.4).
In contrast, compared with the general population, patients with no or moderate response had a significantly increased fully adjusted 1-year risk of ACS, with a hazard ratio of 2.7 (95% CI 1.7-4.4) among nonresponders and a hazard ratio of 2.6 (95% CI 1.5 to 4.4) among moderate responders.
Ljung and co-investigators concluded that the reduction in the short-term risk of ACS in patients with RA and good response on TNF inhibitor treatment indicates "that the ability to reach optimal control of disease activity, rather than merely improved disease control, or TNF inhibitor [use] per se, could potentially normalize the pattern of ischemic heart disease in RA."
Limitations include the lack of data on CV risk factors such as dyslipidemia and family history of CV disease and the observational design of the study.
This study was supported by grants from the Swedish Research Council, the Swedish Rheumatism Association, King Gustav V's 80-Year Foundation, the Västerbotten and Stockholm County Councils, the Swedish Heart-Lung Foundation, the Swedish Foundation for Strategic Research, and the Swedish public-private COMBINE research consortium.
The authors reported no competing interests.
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