IL12/23 blockade with ustekinumab as a treatment for immune-related cutaneous adverse events Journal Article


Authors: Gu, S. L.; Maier, T.; Moy, A. P.; Dusza, S.; Faleck, D. M.; Shah, N. J.; Lacouture, M. E.
Article Title: 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. © 2023 by the authors.
Keywords: adult; clinical article; aged; antibiotic agent; unclassified drug; histopathology; advanced cancer; monotherapy; pancreas cancer; follow up; phenotype; ipilimumab; melanoma; quality of life; neutrophil count; breast cancer; skin biopsy; interleukin 5; steroid; data base; retrospective study; cancer therapy; psoriasis; maculopapular rash; cytokine; immune response; neutrophil; lymphoma; interleukin 6; dermatitis; blood cell count; leukocyte count; tissue microarray; tumor growth; lymphocyte; interleukin 12; pyoderma gangrenosum; antihistaminic agent; measles like rash; programmed death 1 ligand 1; programmed death 1 receptor; immunoglobulin e; adverse event; eosinophil; interleukin 23; infliximab; immune checkpoint inhibitor; nivolumab; dermatologic adverse events; lichenoid; human; male; female; article; pembrolizumab; durvalumab; atezolizumab; immune-related adverse events; avelumab; cemiplimab; ultraviolet phototherapy; immune-related cutaneous adverse event; biologics; ustekinumab; checkpoint inhibitor therapy; immune-related cutaneous adverse events; apremilast; chemicals and drugs; gabapentinoid
Journal Title: Pharmaceuticals
Volume: 16
Issue: 11
ISSN: 1424-8247
Publisher: MDPI  
Date Published: 2023-11-01
Start Page: 1548
Language: English
DOI: 10.3390/ph16111548
PROVIDER: scopus
PMCID: PMC10674871
PUBMED: 38004414
DOI/URL:
Notes: Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- MSK corresponding author is Stephanie Gu -- Source: Scopus
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MSK Authors
  1. Mario E Lacouture
    457 Lacouture
  2. Stephen Dusza
    288 Dusza
  3. David M. Faleck
    50 Faleck
  4. Neil Jayendra Shah
    83 Shah
  5. Andrea Primiani Moy
    32 Moy
  6. Stephanie Gu
    15 Gu
  7. Tara Nicole Maier
    5 Maier