JAK inhibitors have flooded the dermatopharmacologic market with indications for many inflammatory dermatoses. Drs Golant and Del Rosso covered the physiology of this medication class along with important trials and safety data. As a quick reminder of the JAK STAT pathway, extracellular binding leads to JAK-receptor dimerization and phosphorylation of STAT proteins. Dimerized and phosphorylated STAT proteins translocate into the nucleus to activate target gene transcription. The dimerization of the JAK receptor is of particular importance as it is selective for a variety of interleukins and cytokines. While at high concentrations, JAK inhibitors likely would block all JAK receptors, they have selectivity: baricitinib is preferential for both JAK1 and JAK2, while abrocitinib and upadacitinib primarily inhibit JAK1 and secondarily JAK2.
They moved on to review important trials on JAK inhibitors, like the MEASURE UP and JADE MONO trials, and the comparisons against dupilumab. Both doses of upadacitinib were effective in reducing EASI scores and, impressively, pruritus scores within 2 days of treatment in patients with atopic dermatitis. At 16 weeks, more than 60% of patients on upadacitinib 30 mg obtained an EASI 90 compared to <40% of those on dupilumab monotherapy. In JADE COMPARE, which compared abrocitinib and dupilumab while patients were utilizing topical steroids, efficacy between dupilumab and high- and low-dose abrocitinib was similar. JAK inhibitors have been able to achieve more stringent endpoints for atopic dermatitis compared to dupilumab, which may alter our patients’ expectations of treatment response.
Safety is an extremely important topic when discussing JAK inhibitors with patients considering the class-wide black box warning for mortality and major cardiac events. This resulted from a post-marketing study in tofacitinib use for rheumatoid arthritis patients. In atopic dermatitis, acne, headache, and nasopharyngitis are the main adverse events related to treatments. For older patients, there is an increased incidence of herpes zoster, and age-appropriate vaccination should be encouraged. Recommended labs include CBC, CMP, and fasting lipid panel, along with pregnancy, hepatitis, and tuberculosis screening at baseline. CBC, CMP, lipids and CPK should be rechecked every few months.