Pemphigoid After Immune Checkpoint Inhibitors and Other Anti-Neoplastic Medications: A Danish Nationwide Case-Control Study.

Abstract

Background: Immune checkpoint inhibitors have been linked to an increased risk of incident pemphigoid.

Objective: To examine the association between immune checkpoint inhibitor treatment and incident pemphigoid using nationwide data in Denmark, including comparison with other anti-neoplastic medications.

Methods: This was a nationwide matched case-control study in Denmark of cases with incident pemphigoid identified through Danish national registries between 2019 and 2024. Cases were matched 1:100 with population controls on age, sex and index date. Exposure was defined as at least one recorded hospital administration of an immune checkpoint inhibitor within three months before the index date. Odds ratios (ORs) with 95% CIs were estimated using conditional logistic regression. In additional analyses, we examined molecularly targeted therapy and conventional chemotherapy using the same exposure window.

Results: We identified a total of 951 cases of pemphigoid and 95,100 controls. Among cases, 7 (0.74%) had been treated with an immune checkpoint inhibitor compared to 64 (0.07%, OR: 11.05, 95% CI: 5.04-24.22) of controls. In an additional analysis 5 cases (0.53%) had been treated with molecularly targeted therapy and 6 cases (0.63%) had been treated with conventional chemotherapy compared to 262 (0.28%, OR: 1.91, 95% CI: 0.79-4.65) and 250 (0.26%, OR: 2.42, 95% CI: 1.07-5.45) of controls respectively. After adjusting for these other anti-neoplastic medications, the association between immune checkpoint inhibitor exposure and pemphigoid remained statistically significant (OR: 10.41, 95% CI: 4.72-22.94).

Conclusion: Immune checkpoint inhibitor treatment was associated with a substantially increased risk of incident pemphigoid in this Danish nationwide case-control study.