Farzin Khosrow-Khavar, MSc, PhD: Tofacitinib and Cardiovascular Risk in RA

Rheumatology Network interviewed Farzin Khosrow-Khavar, MSc, PhD, to discuss his study “Tofacitinib and risk of cardiovascular outcomes: results from the Safety of TofAcitinib in Routine care patients with Rheumatoid Arthritis (STAR-RA) study.” Khosrow-Khavar is a postdoctoral research fellow associated with the Division of Pharmacoepidemiology and Pharmacoeconomics, as well as the Division of Rheumatology, Inflammation, and Immunity at Brigham and Women's Hospital.

Rheumatology Network: Why did your team initially decide to further analyze safety concerns regarding tofacitinib and increased cardiovascular risk?

Farzin Khosrow-Khavar, MSc, PhD: The primary motivation for this study was reports from FDA-mandated ORAL Surveillance safety trial which indicated a potential increased risk of cardiovascular disease with tofacitinib, compared with tumor necrosis factor inhibitors (TNFi), in patients diagnosed with rheumatoid arthritis (RA). Given that the trial included patients at least 50 years of age and with cardiovascular risk factors, we conducted this study to provide a complete picture and assess the cardiovascular safety of tofacitinib in all patients diagnosed with rheumatoid arthritis who are treated in setting of routine care. In addition, the results from the ORAL Surveillance safety trial provided an opportunity to calibrate our results with the trial findings by applying the inclusion and exclusion criteria of the ORAL Surveillance trial to assess whether our findings are comparable with the trial results.

RN: What was the study design?

FKK: We used a retrospective cohort design using 3 insurance claims data sources in the United States: Optum Clinformatics, IBM MarketScan, and Medicare. We assembled 2 cohorts to examine the cardiovascular safety of tofacitinib. The first cohort, “real-world evidence (RWE),” included all patients diagnosed with rheumatoid arthritis treated in routine care. The second cohort, “RCT-duplicate,” was assembled by applying the inclusion and exclusion criteria of the ORAL Surveillance trial to assess potential heterogeneity of treatment effect among subgroup of patients at least 50 years of age and with cardiovascular risk factors. The primary endpoint of this study was a composite of myocardial infarction or stroke. We assessed the risk of cardiovascular outcomes among patients diagnosed with rheumatoid arthritis who initiated treatment with tofacitinib, in comparison with patients who initiated treatment with tumor necrosis factor inhibitors. To account for difference between patients in these groups, we accounted for potential confounders including demographic variables, rheumatoid arthritis-related variables, comorbidities, comedications, and markers of healthcare utilization.

RN: What were the results of the study?

FKK: The results of this study suggest that tofacitinib, in comparison with tumor necrosis factor inhibitors, is not associated with increased risk of cardiovascular outcomes among all rheumatoid arthritis patients treated in routine care. However, consistent with results from ORAL Surveillance trial, the results suggest that tofacitinib, in comparison with tumor necrosis factor inhibitors, may be associated with increased risk of cardiovascular outcomes in subgroup of patients who are at least 50 years of age and with risk factors for cardiovascular disease or history of cardiovascular disease.

RN: What is the clinical significance of these results?

FKK: Our findings suggest a potential heterogeneity of the cardiovascular effect of tofacitinib among patients diagnosed with rheumatoid arthritis. Thus, in all rheumatoid arthritis patients, tofacitinib, in comparison with tumor necrosis factor inhibitors, was not associated with increased risk of cardiovascular outcomes. However, consistent with findings from the ORAL surveillance trial, tofacitinib, in comparison with tumor necrosis factor inhibitors, was associated with increased risk of cardiovascular outcomes in patients at least 50 years of age and with cardiovascular risk factors or history of cardiovascular disease.

RN: Did the results surprise you?

FKK: The findings were not surprising as results of the ORAL Surveillance trial also suggested heterogeneity of cardiovascular effect by age and specific cardiovascular risk factors. In addition, when emulating the ORAL surveillance trial inclusion and exclusion criteria, we observed similar results as the trial.

RN: Does your team plan on doing any further research on this topic?

FKK: Our team plans to compare the risk of cardiovascular outcomes within the Janus kinase inhibitors drug class among patients diagnosed with rheumatoid arthritis.