(284) Evaluate The Risk of Cardiovascular Event in Rheumatoid Arthritis Patient Receiving Tofacitinib and TNF Inhibitors in Taiwan

Friday, August 26, 2022

8:00 AM – 6:00 PM CEST

Location: Hall C

Publication Number: 615

Presenting Author(s)

Chin-Yao Shen
– NCKU Institute of Clinical Pharmacy and Pharmaceutical Sciences, Institute of Clinical Pharmacy and Pharmaceutical Sciences, Tainan, Tainan, Taiwan

Co-Author(s)

Edward Lai, PhD
– Associate Professor, National Cheng Kung University, National Cheng Kung University, Tainan City, Tainan, Taiwan (Republic of China)

Background: In 2021, based on the review of a large randomized safety clinical trial, US FDA required warnings about the increased risk of serious heart-related events such as heart attack or stroke in rheumatoid arthritis (RA) patients. Due to the ethnic difference, the risk of cardiovascular events (CVEs) in Asians using tofacitinib is, however, uncertain.

Objectives: To evaluate the risk of CVE in Asian individuals with RA using tofacitinib against TNF therapies.

Methods: We conducted a retrospective cohort study by using Taiwan National Health Insurance Database. The RA adult patients (≥ 20 y/o) taking tofacitinib (Tofa) or TNF inhibitors (TNFi) between 2002 and 2018 were observed. The patients with Tofa were defined as the exposure group and the TNFi user, including etanercept, infliximab, adalimumab, certolizumab, golimumab, and opinercept, were in the non-exposure group. Patients who had any history of malignancy, HIV, or auto-immune illness, as well as records of using rituximab, were excluded. The primary outcome was a CVE during hospitalization, including acute coronary disease (ACD), stroke, heart failure (HF), systemic embolism (SE), venous thromboembolism (VTE) and CVE-related death. The patients were followed up on until the first CVE, death or the 31st of December 2018, whichever came first. The incidence rates of CVE were calculated. For the estimated hazard ratio (HR), we used greedy match by the sex, age and the prior number of biological or target synthetic DMARDs (b/tsDMARDs) then applied the Cox proportional hazard model. In the sensitivity analyses, propensity scores were computed and added on the IPTW, SMRW method after the greedy match. Subgroup analysis included the individual results of different kinds of CVE events.

Results: During the study period, 1,992 patients received Tofa while 11,327 patients received TNFi. After the greedy match, there were 1,858 patients in each group. The mean age was 57.1 and 83% are female. About 48% of the patients were new users of TNFi or Tofacitinib and 41% had one b/tsDMARDs before the index drugs. Tofa and TNFi had a CVE rate of 10.0 and 16.5 per 1000 person-years, respectively. The risks of CVE were not different between Tofa and TNFi in main (HR= 0.97; 95% CI: 0.57, 1.62) and sensitivity analyses (IPTW: 0.99 (0.60, 1.68); SMRW: 0.93 (0.54, 1.60)). In the subgroup analysis, the overall result did not find significant differences between Tofa and TNFi due to the small sample size.

Conclusions: This is the first study to look at the risk of CVE in Asian patients taking tofacitinib. The risk is similar in RA patients receiving tofacitinib and TNF inhibitors in Taiwan with a limited follow-up period. Further study for observing the risk under the long-term period of tofacitinib use is still needed.