A Case Series of TNF Inhibitor-Induced Psoriasis Successfully Treated With Upadacitinib
February 2024 | Volume 23 | Issue 2 | e60 | Copyright © February 2024
Published online December 12, 2023
Michael J. Woodbury BSa,c*, Carly Grant BSd*, Lourdes Perez-Chada MD MMSca,c, Avery H. LaChance MDa,c**, Joseph F. Merola MD MMSca,b,c**
aBrigham and Women's Hospital, Department of Dermatology, Boston, MA
bBrigham and Women's Hospital, Department of Medicine, Division of Rheumatology, Boston, MA
cHarvard Medical School, Boston, MA
dMedical College of Wisconsin, Milwaukee, WI
*Co-first author **Co-senior author
Abstract
Tumor necrosis factor-alpha inhibitors (TNF-i) are commonly used to treat immune-mediated diseases such as psoriasis, psoriatic arthritis (PsA), inflammatory bowel disease (IBD), spondyloarthritis (SpA) and rheumatoid arthritis (RA). However, paradoxical psoriasis induced by TNF-i has been described and is not uncommon, particularly with infliximab and etanercept. The presentation of TNF-i-induced psoriasis is most commonly plaque or palmoplantar morphology. Optimal treatment strategies for recalcitrant psoriatic disease are not well understood. In this case series, we report three patients with TNF-i-induced psoriasis who were treated with upadacitinib and experienced complete resolution of their psoriatic eruptions. The efficacy of Janus kinase inhibitors (JAK-i) is possibly explained by mechanisms involving uncontrolled production of type 1 IFNs as well as increases in IL-23 and T-helper 17 cells upstream of relevant JAK/STAT pathways. We also offer a proposed treatment algorithm that includes the use of JAK-i as a promising management option in patients with recalcitrant disease. However, larger studies are needed to confirm the efficacy and safety of JAK-i in this patient population.
J Drugs Dermatol. 2024;23(2): doi:10.36849/JDD.7645
INTRODUCTION
Tumor necrosis factor-alpha inhibitors (TNF-i) treat and are FDA-approved for a wide spectrum of immune-mediated diseases including psoriasis, psoriatic arthritis (PsA), inflammatory bowel disease (IBD), spondyloarthritis (SpA) and rheumatoid arthritis (RA).1 TNF-i-induced paradoxical psoriasis has been well described and is not uncommon given the frequent use of these agents, with a prevalence ranging from 0.6% to 5.3%.2-10 Of the five existing approved TNF-i (adalimumab, infliximab, etanercept, certolizumab, golimumab), infliximab is associated with more than half of these cases (52-62%), followed by etanercept (12-29%).2,11-13 Multiple morphologies may be seen, including plaque psoriasis, palmoplantar pustular psoriasis, guttate, and inverse psoriasis; the most common being plaque (15.8-50%) followed by palmoplantar (33.5-45%).11-15 The mechanism of action remains unclear. It is hypothesized that blocking TNF-alpha allows increased and uncontrolled production of type 1 IFNs by plasmacytoid dendritic cells as well as an increase in IL-23 and T-helper 17 cells.14,16,17 Both axes activate downstream JAK/STAT pathways implicated in disease pathogenesis.22 Standard treatment of care, as detailed in a management algorithm by Li and Merola et al., is to either "treat through" while addressing psoriasis skin manifestations, switch the TNF-i therapy, or switch to a different class.18 However, optimal treatment strategies for recalcitrant psoriatic disease are poorly understood. In this case series, we share the novel use of Janus kinase inhibitors (JAK-i) as promising agents in the management of patients with TNF-i-induced psoriasis as well as an up-to-date proposed treatment algorithm.
