Given the dyslipidemias and increased incidence of various cancers reported during the development of tofacitinib, the FDA required a safety trial comparing RA patients treated with a TNF inhibitor.
This was a randomized, open-label, non-inferiority, post-authorization, safety end-point trial.
The study patients were > 50 years of age with RA and at least one known cardiovascular risk factor. They were equally divided into one of three groups: tofacitinib, 5 mg bid (n=1455); tofacitinib, 10 mg bid (n=1456); or a TNF inhibitor (n-1451).
The primary endpoints after a median duration of follow-up of 4 years were MACEs and cancers. Non-inferiority of tofacitinib was a hazard ratio (HR) < 1.8 compared to a TNF inhibitor.
The incidences of MACEs and cancers in the combined tofacitinib groups were 3.4% and 4.2% compared to 2.5% and 2.9% for the TNF inhibitor group, respectively. The corresponding HRs were 1.33 and 1.48, respectively.
Of note, the incidences of opportunistic infections and non-melanoma skin cancers were higher in the tofacitinib groups than the TNF inhibitor group.