Population-based studies of tofacitinib find no increased risk vs TNFi for cardiovascular or venous thromboembolism outcomes in RA patients.
A population-based study with RA patients initiating treatment with tofacitinib or TNF inhibitors found no statistically significant increased risk associated with tofacitinib for cardiovascular outcomes.
However, like the ORAL surveillance clinical trials, there was a numerical increase in risk for patients with CVD risk factors or history of CVD.
Researchers from Brigham and Women’s Hospital in Boston used deidentified data from US medical claims databases to investigate outcomes in a real-world setting, with findings published in Annals of the Rheumatic Diseases.
The study included two cohorts: a real-world evidence (RWE) cohort of routine care patients and a ‘randomised controlled trial (RCT)-duplicate cohort’ designed to mimic that of the ORAL surveillance trial – that is, patients over 50 years of age with at least one MTX dispensation in the six months prior to cohort entry date, and at least one CV risk factor.
In the RWE cohort, 10% and 13% of patients in the commercial health insurance databases had a history of CVD. The Medicare database, comprised mainly of patients over 65 (the mean age was around 72, compared with early-mid 50s in the other databases), had 31% of patients with a history of CVD.
The pooled weighted hazard ratio (HR) for CV outcomes when comparing tofacitinib with TNFi was 1.01 (95% CI 0.83 to 1.23). Among those who had a history CVD, the HR was 1.27 (0.95-1.70) compared to 0.81 (0.61 to 1.07) without CVD history.
In the RCT-duplicate cohort, the pooled weighted HR for primary outcomes was 1.24 (0.90 to 1.69) – comparable to that of the ORAL surveillance figures, which reported an HR of 1.33 (0.91 to 1.94).
A major strength of the study was the large number of patients: almost 90,000 in the TNFi RWE groups and over 12,000 in the tofacitinib groups. The RCT-duplicate cohort included over 31,000 TNFi patients and almost 3,500 tofacitinib patients (ORAL surveillance data included almost 3000 tofacitinib and 1500 TNFi patients).
The authors concluded that overall, tofacitinib was not associated with risk of composite CV outcomes in RA patients treated in real-world settings.
“However, among patients with CV risk factors or history, estimates consistently suggested a potentially elevated risk,” wrote the authors. “We recommend continuing research to better understand risk-benefit trade-offs of this important treatment option in a wide range of patients with RA.”
Also needed, said the authors, are mechanistic studies to determine how tofacitinib may increase risk of CV events.
A second study by the Brigham and Women’s Hospital group investigated incidence of VTE in RA patients initiating tofacitinib and TNF inhibitors using data from the medical claims databases. The study was published online in Rheumatology last year and in January this year in print.
Patients with cancer or history of VTE during the baseline period were excluded, as were patients with prior use of b/tsDMARDs. Propensity score-weighted HRs showed no significant differences between tofacitinib and TNFi initiators VTE risk, with a pooled adjusted HR of 1.13 (0.77-1.65). Similar findings were observed for DVT and PE components.
Strengths of the study include the large patient base (almost 7000 on tofacitinib and over 80,000 on TNFi) and rigorous confounding adjustment. However, a limitation of the study was potential residual confounding by factors not measured in administrative claims, such as disease activity and physical activity.
The authors concluded there’s no evidence for increased risk of VTE for patients on the lower dose tofacitinib (5mg BID) compared with patients on TNF inhibitors.
“Added risk of adverse CV and VTE events with 5mg tofacitinib appears to be low in patients with no underlying risk factors,” co-author Dr Rishi Desai told Rheumatology Republic.
“These results are consistent with pooled data from previous clinical trials of 5mg tofacitinib and a large registry of RA patients from the US. Among patients with underlying CV illness or risk factors, our results coincide with observations of potentially elevated risk from ORAL Surveillance. We recommend and await confirmation of these finding in future studies from across the globe,” he said.
