Off-Label Use of Janus Kinase Inhibitors in Inflammatory Cutaneous Diseases

Dysregulation of Janus kinase (JAK) pathways from uncontrolled cytokine signaling comprises the pathological basis for many complex inflammatory cutaneous disorders. Oral JAK inhibitors, upadacitinib, tofacitinib, and baricitinib targeting JAK 1 and JAK 1/3, respectively, are currently US Food and Drug Administration (FDA)-approved for several rheumatic conditions. However, studies have shown that JAK-mediated signaling pathways are involved in many immune-related dermatologic conditions. As a result, for recalcitrant diseases, JAK inhibitors are potential alternative therapies due to their broad targeted inhibitory mechanisms. In this case series, we present the successful off-label treatment of 6 cases across dermatomyositis, hidradenitis suppurativa, cutaneous lupus, and cutaneous Crohn’s disease, which failed conventional therapies with upadacitinib or tofacitinib. In the 3 dermatomyositis cases, use of upadacitinib or tofacitinib demonstrated positive clinical outcomes, with no recurrent symptoms in cases where upadacitinib was used. In treatment-resistant hidradenitis suppurativa, upadacitinib demonstrated reduced systemic flares and moderate cutaneous symptom improvement. In the case of cutaneous Crohn’s disease, upadacitinib resulted in reduced cutaneous symptoms without new flares. Tofacitinib resulted in completed resolution of cutaneous symptoms in our patient’s case of cutaneous lupus erythematosus. JAK inhibitors upadacitinib and tofacitinib may be potential drug candidates in patients with treatment-resistant disease, especially in cases of inflammatory cutaneous conditions such as dermatomyositis, hidradenitis suppurativa, cutaneous lupus, and cutaneous Crohn’s disease. Further studies with larger sample sizes among these conditions are warranted to assess potential broader applicability of the positive results demonstrated in our patient cases. J Drugs Dermatol. 2023;22(12):1183-1190. doi:10.36849/JDD.7500.