Effectiveness of Upadacitinib in Patients with Atopic Dermatitis including those with Inadequate Response to Dupilumab and/or Baricitinib: Results from the BioDay Registry

Abstract

Clinical trials showed that upadacitinib, a selective Janus kinase-1 inhibitor, is effective for treatment of moderate-to-severe atopic dermatitis. However, daily practice studies are limited. This multicentre prospective study evaluated the effectiveness of 16 weeks of upadacitinib treatment for moderate-to-severe atopic dermatitis in adult patients, including those with previous inadequate response to dupilumab and/or baricitinib, in daily practice. A total of 47 patients from the Dutch BioDay registry treated with upadacitinib were included. Patients were evaluated at baseline, and after 4, 8 and 16 weeks of treatment. Effectiveness was assessed by clinician- and patient-reported outcome measurements. Safety was assessed by adverse events and laboratory assessments. Overall, the probabilities (95% confidence intervals) of achieving Eczema Area and Severity Index ≤ 7 and Numerical Rating Scale – pruritus ≤ 4 were 73.0% (53.7–86.3) and 69.4% (48.7–84.4), respectively. The effectiveness of upadacitinib was comparable in patients with inadequate response to dupilumab and/or baricitinib and in patients who were naïve for these treatments or who had stopped such treatments due to adverse events. Fourteen (29.8%) patients discontinued upadacitinib due to ineffectiveness, adverse events or both (8.5%, 14.9% and 6.4%, respectively). Most frequently reported adverse events were acneiform eruptions (n = 10, 21.3%), herpes simplex (n = 6, 12.8%), nausea and airway infections (both n = 4, 8.5%). In conclusion, upadacitinib is an effective treatment for patients with moderate-to-severe atopic dermatitis, including those with previous inadequate response to dupilumab and/or baricitinib treatment.

Dupilumab, Atopic Dermatitis, and Mycosis Fungoides—New Insights on an Evolving Story

“…The histopathologic findings of LR as described by the authors, is characterized by large CD30-positive T cells with altered CD4:CD8 T-cell ratios, retention of pan–T-cell markers, and peppering of small lymphocytes involving all epidermal layers. This description overlaps with transformed MF, as well as other lymphoproliferative conditions, like lymphomatoid papulosis.…”

“…There is currently insufficient evidence to report such reactions as benign and thus a cautious descriptive diagnostic approach refraining from MF overdiagnosis is recommended. I commend Boesjes et al 1 for their astute observation. We have certainly observed similar cases at the Northwestern Cutaneous Lymphoma Clinic with resolution on discontinuation of dupilumab, but concerns for the several reports of irreversible and often aggressive disease acceleration in previously undiagnosed patients with MF remains.…”

“…Among the 14 patients in the cohort in the study by Boesjes et al initially treated with dupilumab for presumed AD, who later experienced worsening symptoms, 3 were diagnosed with MF and 11 with LR. The authors introduce the concept that some of these dupilumab-induced atypical presentations may not denote progression to MF.…”

“…In this issue of JAMA Dermatology, Boesjes et al 1 share their experience with patients with presumed atopic dermatitis (AD) who, shortly after dupilumab initiation, experienced worsening skin symptoms unlike their previous disease. Skin biopsies were characterized by atypical T-cell lymphocytic infiltrates.…”

“…Among the 14 patients in the cohort in the study by Boesjes et al initially treated with dupilumab for presumed AD, who later experienced worsening symptoms, 3 were diagnosed with MF and 11 with LR. The authors introduce the concept that some of these dupilumab-induced atypical presentations may not denote progression to MF. Although the test of time and additional data are required to understand the true nature of such reactions, their findings contribute to the evolving literature by describing potentially reversible lymphomatoid drug reactions and offering additional insights into their clinical and pathologic features.…”