Boxed Warnings: What Do They Really Mean To You?
Associate Professor of Dermatology
Yale University School of Medicine
New Haven, CT
The approval of multiple novel JAK inhibitors for inflammatory dermatoses such as atopic dermatitis and alopecia areata has left many dermatologists wondering how to deal with the FDA-mandated class-wide black box warning. All oral JAK inhibitors carry a warning for serious infection, malignancy, major adverse cardiovascular events (MACE), all-cause mortality, and thrombosis. Christopher G. Bunick, MD, PhD, used this session to bust some common myths associated with black box warnings. Contrary to popular belief, a causal relationship between a medication and an adverse event does have to be established for a drug to carry a specific warning. FDA application of black box warnings is increasing according to Dr Bunick, so dermatologists should become comfortable discussing them with patients.
Dr Bunick went on to discuss that medications with black box warnings can be purchased over the counter, as evidenced by ibuprofen, which carries a black box warning for cardiovascular thrombotic events and gastrointestinal events. There are many other medications commonly used in dermatology that carry boxed warnings, including TNF- inhibitors, isotretinoin, botulinum toxins, and multiple antimicrobials. To conclude, Dr Bunick reviewed safety data for JAK inhibitors compared with conventional immunosuppressives that have been commonly used for atopic dermatitis. A recent review found that both upadacitinib and abrocitinib have lower rates of malignancy, MACE, and thrombosis than methotrexate, cyclosporine, and systemic corticosteroids when used in patients with atopic dermatitis. Rates of malignancy, MACE, and thrombosis in patients with atopic dermatitis on JAK inhibitors are also equal to or lower than rates in patients with untreated moderate-to-severe atopic dermatitis.