IL12/23 Blockade with Ustekinumab as a Treatment for Immune-Related Cutaneous Adverse Events

Abstract

Background: Immune-related cutaneous adverse events (ircAEs) are frequent and may reduce quality of life and consistent dosing. IL12/23 has been implicated in psoriasis, which is reminiscent of the psoriasiform/lichenoid ircAE phenotype. We report the use of ustekinumab as a therapeutic option. Methods: Patients at Memorial Sloan Kettering Cancer Center, New York, who received immune checkpoint inhibitors and were treated with ustekinumab or had the keywords "ustekinumab" or "Stelara" in their clinical notes between 1 March 2017 and 1 December 2022 were retrospectively identified via a database query. Documentation from initial and follow-up visits was manually reviewed, and response to ustekinumab was categorized into complete cutaneous response (CcR, decrease to CTCAE grade 0), partial cutaneous response (PcR, any decrease in CTCAE grade exclusive of decrease to grade 0), and no cutaneous response (NcR, no change in CTCAE grade or worsening). Labs including complete blood count (CBC), cytokine panels, and IgE were obtained in a subset of patients as standard of care. Skin biopsies were reviewed by a dermatopathologist. Results: Fourteen patients with psoriasiform (85.7%), maculopapular (7.1%), and pyoderma gangrenosum (7.1%) ircAEs were identified. Ten (71.4%) receiving ustekinumab had a positive response to treatment. Among these 10 responders, 4 (40%) demonstrated partial cutaneous response and 6 (60%) demonstrated complete cutaneous resolution. Six patients (42.9%) experienced interruptions to their checkpoint inhibitor treatment as a result of intolerable ircAEs, and following ircAE management with ustekinumab, two (33.3%) were successfully rechallenged with their checkpoint inhibitors. On histopathology, patients primarily had findings of interface or psoriasiform dermatitis. No patients reported an adverse event related to ustekinumab. Conclusions: Ustekinumab showed a benefit in a subset of patients with psoriasiform/lichenoid ircAEs. No safety signals were identified. However, further prospective randomized controlled trials are needed to confirm our findings.

Keywords: biologics; dermatologic adverse events; immune-related adverse events; immune-related cutaneous adverse events; ustekinumab.

Figure 1

Representative clinical image of patient with palmoplantar psoriasis who received treatment with UST.

Figure 2

Swimmer’s plot of the time in therapy for both ICB therapy (colored bars) and ustekinumab (black bars), along with the timing of specific events within the treatment the course (n = 14). NcR= cutaneous non-responder to ustekinumab, cR = cutaneous responder to ustekinumab, IrcAE = immune-related cutaneous adverse event, CcR = complete cutaneous response to ustekinumab, PcR = partial cutaneous response to ustekinumab.

Figure 3

Two-way bar chart of the proportion of patients on specific treatments prior to and concurrent with ustekinumab (n = 14).