Cardiovascular comobidities in RA patients

The increased cardiovascular risks in RA include acute coronary syndromes (ACS). The extent to which DMARD-induced remission could reduce the risk of ACS in RA versus rates in the general population – and whether there are DMARD-specific beneficial effects on ACS risk – remain unknown. In a session titled, From hearts to lungs: comobidities in RA, Delcoigne and colleagues present new data on the risk of ACS in patients with RA who attained remission with methotrexate (MTX) or a tumor necrosis factor inhibitor (TNFi).

The researchers defined and pooled cohorts of RA patients from registers in Norway and Sweden. This included 14,488 treatment courses with MTX and 13,056 with TNFi. Everyone had started MTX or a TNFi between 2012 and 2021, and were followed for 1 year from the first date at which remission was recorded until any ACS, death, emigration, treatment discontinuation, a new DMARD start, first non-remission date, or end of the study.

DAS28 remission was achieved in 40% and 32% of MTX- and TNFi-treated patients. During the 1-year follow-up there were 15 and 12 ACS events in the MTX and TNFi cohorts, respectively – corresponding to crude incidence rates of 3.4 and 3.8 per 1000 person-years. Comparing these incidence rates gave a hazard ratio (HR) of 1.19 for TNFi versus MTX. Other remission metrics provided similar and statistically non-significant estimates. The comparison of treated (MTX or TNFi) patients in remission to the general population provided a HR of 1.08, adjusted for age, sex and calendar year.

Patients with RA who reach remission on MTX have a similar ACS risk as those reaching remission on TNFi. The incidence rates of ACS in patients in remission were comparable to the incidence rate in the general population."

Bénédicte Delcoigne, Karolinska Institutet in Stockholm, Sweden

A second abstract from Buch and colleagues looked at the impact of cardiovascular comorbidities on the efficacy of tofacitinib versus TNFi in RA. This was based on the observation that RA patients with a history of atherosclerotic cardiovascular disease (HxASCVD) have a higher risk of major adverse CV events (MACE) with tofacitinib versus TNFi, whereas risk difference is not detected in people with no HxASCVD. The researchers used data from ORAL Surveillance – an open-label, post-authorization safety study that included patients with active RA despite MTX, Everyone was aged 50 or older, and had at least one additional CV risk factor. In this post hoc analysis, patients were categorized by HxASCVD. For those with no HxASCVD, the 10-year risk of ASCVD was determined using pooled cohort equations with a multiplier applied per EULAR guidelines.

Of 4,362 patients, 640 had a HxASCVD, and 3722 had no HxASCVD. The results showed that in those with no HxASCVD, the efficacy of tofacitinib was at least as good as TNFi, and risk of MACE was comparable. RA patients with high or intermediate cardiovascular risk scores tended to be more likely to reach remission or low disease activity with tofacitinib versus TNFi, as were patient with low–borderline risk scores who received tofacitinib 10 mg twice daily.

The authors suggest that, in RA patients with a history of ASCVD, clinicians should consider that the risk of MACE with tofacitinib is higher versus TNFi, while efficacy is similar.

Maya Buch, lead author on the abstract said "Overall, these findings further characterize the benefit–risk of tofacitinib by cardiovascular risk category, and provide a means to risk-stratify patients such that tofacitinib can be considered an effective treatment option where appropriate."

Similar work was shared by Aymon and colleagues, in their abstract on the incidence of MACE in RA patients treated with janus kinase inhibitors (JAKi) compared to bDMARDs. This real-world data includes 14 RA registries from an international collaboration called the 'JAK-pot study'. Patients starting JAKi, TNFi, or bDMARDs with other modes of action (OMA), were included. A sub-analysis was performed mimicking the ORAL Surveillance inclusion criteria: patients aged at least 50 years and with one or more cardiovascular risk factor.

Over the 50,325 treatment initiations considered, there were 182 incident MACE reported. The study did not find a significantly higher risk of MACE in RA patients treated with JAKi compared to TNFi. Crude MACE incidence was higher for OMA than for JAKi and TNFi, but the adjusted regression analysis demonstrated no significant difference in the incidence of MACE between JAKi versus TNFi and OMA versus TNFi.

The ORAL Surveillance duplicate cohort accounted for 38.4% of treatment courses and had a higher incidence of MACE in each treatment group. But similarly to the overall population, there was no significant difference in the incidence of MACE observed between JAKi versus TNFi and OMA versus TNFi.

The authors note that inclusion of other registers to increase the statistical power and the evaluation of other adverse events such as thromboembolic events, cancers, and serious infections are planned.