In the ORAL Surveillance study, researchers found tofacitinib showed a higher incidence of pulmonary embolism compared with tumor necrosis factor inhibitors (TNFi) in the treatment of patients aged 50 or more years with rheumatoid arthritis and 1 or more additional cardiovascular risk factor.
A post hoc analysis attempted to identify biomarkers that explained the association between tofacitinib and venous thromboembolism (VTE) that was absent with TNFi treatment.
Increased VTE Rate With Tofacitinib Versus TNFi in RA
According to the authors, none of the 291 protein or 3 genetic biomarkers they analyzed provided a mechanistic explanation for the increased rate of VTE seen in patients who received tofacitinib, which authors noted was most prominently increased in patients who took a dose of 10 mg twice daily.
The ORAL Surveillance study was a prospective, open-label safety study that randomized 4362 patients 1:1:1 to twice-daily tofacitinib 5 mg or 10 mg, or a TNFi. Markers were reviewed in serum samples from baseline, 12 months, and the study’s end.
Of the 294 exploratory biomarkers, 79 had a role inflammation, coagulation, vascular biology, or Janus kinase signalling, the authors noted. A total of 285 participants were reviewed, of which 57 had VTE events and 228 were matched controls. D-dimer levels were also assessed in 54 VTE cases and 3678 controls.
According to the researchers, none of the biomarkers showed a clear mechanistic association with the increased VTE risk in patients receiving tofacitinib versus those receiving TNFi; however, the authors did find that D-dimer levels at month 12 were positively associated with risk for subsequent VTE in both of the tofacitinib treatment groups.
Ultimately, the investigators suggested “individual VTE risk should be considered when making decisions about initiation or maintenance of tofacitinib treatment,” and advised that “the decision to monitor D-dimer levels should be made by clinicians on an individual patient basis…”
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