NEJM published study leading to boxed warning
Just a week prior to the CRA annual meeting, the New England Journal of Medicine published an FDA-mandated postmarketing trial of tofacitinib that was used by the agency to justify the boxed warning for JAKi with indications for artitis and other inflammatory diseases. In that open-label trial, more than 4,000 patients aged 50 years or older with at least one additional cardiovascular risk factor were randomized to 5 mg tofacitinib twice daily, 10 mg tofacitinib twice daily, or a TNFi (adalimumab or etanercept).
The efficacy of the therapies was similar, but tofacitinib failed to meet predefined noninferiority criteria for the co–primary endpoints of MACE or cancer (excluding nonmelanoma skin cancer). For tofacitinib relative to TNFi, the hazard ratio was 1.33 for MACE and 1.48 for cancers. The JAKi was also associated with higher incidences of opportunistic infections.
Mr. Iskander noted that Canadian clinical practice guidelines currently identify JAKi as a reasonable first-line alternative to bDMARDs after inadequate response to csDMARDs. While his data support that position, Dr. Twilt indicated that the benefit-to-risk ratio of JAKi might need recalculation based on the data that led the FDA to issue its boxed warning. She questioned whether the language regarding the relative role of JAKi and bDMARDs will change in coming RA guideline revisions.
Dr. Iskander reported no potential conflicts of interest. Dr. Movahedi did not list any personal conflicts of interest but acknowledged that OBRI received unrestricted grants from a variety of pharmaceutical companies, including those that manufacture bDMARDs and JAKi. Dr. Twilt reported no potential conflicts of interest.