Immune checkpoint inhibitors and the pediatric rheumatologist: a pediatric needs assessment

TL;DR

Pediatric rheumatologists lack knowledge and confidence in managing immune-related adverse events from cancer treatments, highlighting a need for education and guidelines.

Contribution

This study identifies significant knowledge gaps and confidence issues among pediatric rheumatologists regarding immune checkpoint inhibitor-related adverse events.

Findings

Most pediatric rheumatologists are unfamiliar with immune checkpoint inhibitors and their side effects.

Few have managed immune-related adverse events, and none feel completely confident in doing so.

Respondents requested pediatric-specific clinical guidelines for managing these conditions.

Abstract

The use of immune checkpoint inhibitor (ICI) therapy is increasing in pediatric oncology. ICIs can cause rheumatic-immune related adverse events (Rh-irAEs) such as inflammatory arthritis and myositis. Few case reports detail Rh-irAEs and their management in the pediatric population. Our objective was to assess the familiarity of pediatric rheumatologists (PRs) worldwide with Rh-irAEs, gauge confidence in managing these conditions, and identify knowledge gaps to guide future educational efforts.

We circulated an online survey to 2084 PRs via the “Dr. Peter Dent Pediatric Rheumatology Bulletin Board.” Responses were collected from June 2024 to September 2024. We collected data on practitioner demographics, knowledge of ICIs and Rh-irAEs, confidence in managing Rh-irAEs, and preferred educational resources.

Sixty-nine participants responded, of which 55 (80%) were PRs from academic centers. Despite global distribution, 56 (81%) responses came from North America. Thirty-four (49%) respondents were not aware of ICIs and their related mechanisms, indications, and side effects, and 40 (58%) were not familiar with irAEs. Fifty-five (80%) had never managed a patient with Rh-irAEs. Among those who had (14/69, 21%), the median number of cases managed was 2.0 (IQR 0.0). Thirty-nine respondents were “not confident at all” managing Rh-irAEs, 34 were “not confident at all” managing pre-existing autoimmune diseases (PAD) in ICI users, and 46 were “not confident at all” advising oncology colleagues on initiating or discontinuing ICIs in the context of Rh-irAEs or pre-existing autoimmune diseases (PAD). No respondents felt “completely confident” managing these conditions. Participants identified knowledge gaps in long-term management, acute management, and recognition and diagnosis. Forty-three indicated the need for pediatric-specific clinical guidelines. Of the 14 respondents with clinical experience treating Rh-irAEs, treatment varied, with 4 using nonsteroidal anti-inflammatory drugs, 3 using prednisone, and 4 combining prednisone with methotrexate. Long-term management also varied, with 5 using methotrexate, and 3 using tumor necrosis factor inhibitors.

Significant knowledge gaps and a lack of confidence exist among PRs managing ICI-related Rh-irAEs. As ICI use increases in pediatric oncology, PRs’ exposure to Rh-irAEs will follow. Targeted educational programs and clinical guidelines may be valuable to address these gaps.

The online version contains supplementary material available at 10.1186/s12969-025-01127-x.

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