TOPLINE:

Significantly improved 5-year survival was linked to receiving dupilumab treatment for cutaneous immune-related adverse events following immune checkpoint inhibitor therapy when compared with patients in nontreatment and systemic corticosteroid groups. Patients treated with dupilumab demonstrated a 76% lower risk for mortality compared with untreated patients and a 69% lower risk compared with those receiving systemic corticosteroids.

METHODOLOGY:

• Dupilumab is a monoclonal antibody targeting the interleukin-4 receptor alpha subunit. The medication has been utilized off-label for managing cutaneous immune-related adverse events following immune checkpoint inhibitor therapy. Prior research has evaluated survival within a single healthcare network, but broader analyses across larger, geographically diverse populations have been lacking.
• Researchers conducted a retrospective cohort study using de-identified aggregate data from the TriNetX Global Collaborative Network, following the Strengthening the Reporting of Observational Studies in Epidemiology guideline.
• Analysis included 204 adults who developed cutaneous immune-related adverse events and received dupilumab, with two 1:1 propensity score-matched comparison cohorts: patients with cutaneous immune-related adverse events never prescribed dupilumab (control group 1) and those prescribed systemic corticosteroids without dupilumab (control group 2).
• Participants were matched for age, sex, race and ethnicity, Charlson Comorbidity Index diagnoses, and use of other immunomodulatory agents, with analyses conducted from March 28, 2017, to October 16, 2025.
• Primary endpoint was all-cause mortality, while secondary endpoints included noncutaneous immune-related adverse events, healthcare utilization, and infections, with hazard ratios (HRs) calculated at 5 years after cutaneous immune-related adverse events onset.

TAKEAWAY:

• Dupilumab-treated patients (mean age, 72.8 ± 11.4 years; 33.3% women) showed significantly improved survival compared with control groups 1 (HR, 0.24; 95% CI, 0.15-0.36) and 2 (HR, 0.31; 95% CI, 0.21-0.47; P < .001 for both).
• Sensitivity analyses reindexing at 180 days post cutaneous immune-related adverse events onset confirmed survival benefits for control groups 1 (HR, 0.37; 95% CI, 0.23-0.59) and 2 (HR, 0.43; 95% CI, 0.27-0.68; P < .001 for both).
• Median survival was 903 and 1438 days in control groups 1 and 2, respectively, while not reached in dupilumab-treated patients.
• The relative risk of developing noncutaneous immune-related adverse events was higher in dupilumab-treated patients compared with those in control group 1 (relative risk, 1.46; 95% CI, 1.01-2.12; P = .047), particularly for gastrointestinal events (relative risk, 1.76; 95% CI, 1.02-3.03; P = .04), though these differences were not significant after Bonferroni correction.

IN PRACTICE:

“Dupilumab lacks broad immunosuppressive effects, making it optimal for treating atopic dermatitis in patients with cancer. Although dupilumab’s ability to control symptoms in patients with [cutaneous immune-related adverse events] is well established, long-term outcomes remain uncertain,” the authors of the research letter wrote.

SOURCE:

The research was led by Brandon Block, Department of Dermatology, Icahn School of Medicine at Mount Sinai in New York City. It was published online on January 22 in JAMA Oncology.

LIMITATIONS:

According to the authors, the study design introduces immortal-time bias relative to nonuse, although this is partially mitigated by sensitivity analyses. Additionally, some dupilumab-treated patients may have previously received systemic corticosteroids, as the study was indexed at cutaneous immune-related adverse event onset. The researchers noted that considering residual and unmeasured confounders, the large effect sizes must be interpreted with caution.

DISCLOSURES:

Thomas Marron, MD, PhD, reported receiving research grants and personal fees for advisory board service from Regeneron outside the submitted work. No other disclosures were reported.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.