Incidence of CV Events, Malignancies, and Venous Thromboembolism in Patients with RA According to Baseline CV Risk and Administered Treatment

Introduction

The ORAL Surveillance study evaluated the safety of tofacitinib compared to TNF inhibitors in patients with rheumatoid arthritis over the age of 50 who had ≥ 1 additional CV risk factor and showed inadequate response to methotrexate treatment. Given that CV risk factors overlap with risk factors for oncological diseases and VTE, this post hoc analysis of data from the mentioned study focused on the impact of baseline CV risk and administered treatment on the occurrence of these events.

Methods and Study Design

Patients with a stable dose of methotrexate were randomized in a 1:1:1 ratio to receive tofacitinib at a dose of 10 mg twice daily, tofacitinib 5 mg twice daily, or a TNF inhibitor, either adalimumab at a dose of 40 mg every 2 weeks or etanercept at a dose of 50 mg once weekly. The occurrence of major adverse cardiovascular events (MACE) defined as CV deaths excluding deaths due to pulmonary embolism, non-fatal myocardial infarction, or non-fatal stroke, as well as the occurrence of malignancies excluding non-melanoma skin cancers and the occurrence of VTE including both fatal and non-fatal cases of deep vein thrombosis and pulmonary embolism were assessed.

The analysis included the incidence (number of patients with the first event per 100 patient-years) and the risk levels of these events during treatment with tofacitinib in specific doses compared to TNF inhibitors. Both incidence rates and risk ratios were stratified according to the baseline CV risk score of the patients. Patients were categorized into a group with a positive history of ischemic heart disease (IHD) and into 4 groups based on CV risk score: high (≥ 20%), intermediate (≥ 7.5% to < 20%), borderline (≥ 5% to < 7.5%), and low (< 5%). This risk was determined by multiplying the ASCVD score (according to the American Heart Association) by 1.5× as recommended by EULAR.

Results

Data from 4362 patients were analyzed. At study entry, IHD, high, or intermediate CV risk was present in 2/3 of the enrolled patients, and the distribution of CV risk was comparable across therapeutic groups.

After a median follow-up of 4 years, MACE was reported in 3.5% of patients on tofacitinib 10 mg, 3.2% on tofacitinib 5 mg, and 2.6% on TNF inhibitors. The incidence of malignancies in these therapeutic groups was 4.1%, 4.3%, and 2.9%, respectively, and the incidence of VTE was 2.3%, 1.2%, and 0.7%, respectively.

MACE and malignant tumors showed the highest incidence in patients with IHD or high CV risk across all treatment groups. Incidence rates were generally higher with tofacitinib compared to TNF inhibitors, with the difference in the occurrence of MACE and malignancies being more pronounced in patients with IHD or at least intermediate CV risk. The incidence of VTE and the risk of VTE compared to TNF inhibitors were significantly higher in patients treated with tofacitinib 10 mg, who had IHD or high CV risk score at study entry. No connection between VTE and baseline CV risk score was observed with tofacitinib 5 mg or TNF inhibitor treatment.

Conclusion

Post hoc analysis of data from the ORAL Surveillance study showed a higher risk of major CV events and malignant tumors in patients with rheumatoid arthritis over the age of 50 not adequately controlled by methotrexate with ≥ 1 additional CV risk factor, who had a history of ischemic heart disease or high CV risk score at study entry. This risk was higher with tofacitinib treatment compared to TNF inhibitors, and tofacitinib at a dose of 10 mg was also associated with a higher risk of deep vein thrombosis than adalimumab/etanercept in patients with IHD or high CV risk score at study entry. Based on these findings, the authors recommend regular assessment and management of CV risks in patients with rheumatoid arthritis.

(zza)

Source: Buch M. H., Charles-Schoeman C., Curtis J. et al. POS0237 Major adverse cardiovascular events, malignancies and venous thromboembolism by baseline cardiovascular risk: a post hoc analysis of ORAL Surveillance. Ann Rheum Dis 2022; 81: 356−357, doi: 10.1136/annrheumdis-2022-eular.1182.