JAK of All Trades: Novel Off-Label Use of the Systemic JAK Inhibitor Upadacitinib As An Adjunct to Systemic Biologic Therapy for Various Immune-Mediated Inflammatory Diseases of the Skin

Background: While monotherapy with systemic biologics is effective in most patients with immune- mediated inflammatory diseases (IMIDs) of the skin, some may have recalcitrant disease warranting the addition of another systemic non-biologic. Upadacitinib (UPA) is a systemic Janus kinase (JAK) inhibitor approved for several IMIDs. Combining systemic biologics and systemic JAK inhibitors may provide a greater reduction in disease severity; however, no rigorous studies have assessed such an approach. In this retrospective case series, we highlight the novel off-label use of UPA as an adjunct to various systemic biologics. Eleven patients with moderate-to-severe IMIDs of the skin (Investigator Global Assessment [IGA] >= 3), including atopic dermatitis, (1/11), dermatitis/plaque psoriasis overlap (3/11), plaque psoriasis (4/11), psoriasiform drug eruption (1/11), and pustular psoriasis (2/11) were treated with UPA and a systemic biologic (brodalumab, guselkumab, and risankizumab [n=2 for each]; adalimumab, dupilumab, etanercept, infliximab, and secukinumab [n=1 for each]). The mean patient age was 54.9 years (range: 33-76 years). Of the 11 patients (3 females; 8 males), IGA was improved in all cases (11/11), with 91% (10/11) achieving IGA 0/1 (clear or almost clear) between 12 and 32 weeks after adding UPA to the systemic biologic. With 4.6 patient years of total follow-up, no serious adverse events (AEs) were reported, although one patient experienced mild gastrointestinal upset; there were no AE- related treatment discontinuations or deaths. Our case series shows that off-label use of UPA in conjunction with systemic biologics is effective and safe. Randomized controlled trials and long-term studies are warranted to confirm these findings.