Smoking, older age put patients receiving tofacitinib at higher risk for MACE vs. TNFi
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Key takeaways:
- Older age, history of smoking indicates a higher risk for adverse events while taking tofacitinib.
- Low-risk patients did not see an increased risk of adverse events.
Patients aged 65 years and older or who have ever smoked are at higher risk for malignancies, major adverse cardiovascular events, myocardial infarction and all-cause death when using tofacitinib vs. TNF inhibitors, according to data.
Meanwhile, patients aged younger than 65 years who have never smoked demonstrated no apparent increased risk when receiving tofacitinib (Xeljanz, Pfizer), compared with TNF inhibitors, for up to 6 years of follow-up.
The data come from a post hoc analysis of the ORAL Surveillance trial.
“To ensure enough cardiovascular (CV) and malignancy events accrued in a reasonable timeframe, ORAL Surveillance enrolled patients with [rheumatoid arthritis] with higher-than-average risk; patients had to be at least 50 years old and have at least one additional CV risk factor,” Lars Erik Kristensen, MD, of the Parker Institute, at Bispebjerg and Frederiksberg Hospital, in Copenhagen, Denmark, and colleagues wrote in the Annals of the Rheumatic Diseases.
“Previous studies have shown a relationship and shared risk factors between CV disease and malignancy, for example, data from Dutch and U.S. cohorts found an association between the 10-year atherosclerotic cardiovascular disease (ASCVD) risk scores and risk of future cancer,” they added. “Importantly, a wide range of CV risk factors were applied as eligibility criteria, therefore, a 52-year-old with mild hypertension and a 71-year-old with prior myocardial infarction (MI) would both have been eligible despite very different risk levels. Indeed, enrolled patients were found to be distributed across a continuum of risk.”
To determine groups of patients that might be at higher or lower risk levels while receiving tofacitinib, compared with TNF inhibitors, Kristensen and colleagues conducted a post hoc analysis of ORAL Surveillance, a phase 3b/4 trial that investigated the noninferiority and safety of tofacitinib vs. TNF inhibitors. Patients in ORAL Surveillance were randomized 1:1:1 to receive either oral tofacitinib 5 mg, tofacitinib 10 mg or a TNF inhibitor. In North America, patients received adalimumab (Humira, AbbVie), while in other parts of the world they received etanercept (Enbrel, Amgen).
This current analysis included patients with RA, ulcerative colitis or psoriatic arthritis who received one or more doses of tofacitinib. Kristensen and colleagues focused specifically on adverse events, including the development of malignancies aside from non-melanoma skin cancer, major adverse cardiovascular events, fatal and non-fatal myocardial infarction, venous thromboembolism and all-cause death. Major adverse cardiovascular events included death attributed to cardiovascular events, non-fatal myocardial infarction and non-fatal strokes.
According to Kristensen and colleagues, a subgroup of patients aged 65 years and older or who had ever smoked demonstrated a higher risk for developing cancer, major cardiovascular events, venous thromboembolism or all-cause death if they received tofacitinib vs. TNF inhibitors (HRs = 1.41-5.19; 95% CI).
In patients considered low risk — specifically those aged younger than 65 years who had never smoked — there was no increased risk for the measured outcomes (HRs = 1; 95% CI) throughout 6 years of follow-up. Additionally, absolute risk remained low and was corroborated among patients with RA, PsA and ulcerative colitis for up to 10 years.
“In this post hoc analysis, two clinically practical and easily identifiable subpopulations were found that demarcated tofacitinib-treated patients with increased risk of these events from patients with similar risk relative to TNFi-treated patients,” Kristensen and colleagues wrote. “Given the design of ORAL Surveillance, enough events accrued to allow for post hoc identification of patients at higher risk with tofacitinib versus TNFi.”
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