(240) Off-label use of thalidomide in pediatric patients with Crohn's disease and other subtypes of inflammatory bowel disease: a literature review

Background: Thalidomide is a drug with immunomodulatory properties used to treat various conditions. While its effectiveness in treating Crohn's disease (CD) in pediatric patients has been shown in some studies, the safety of this off-label use is not well established.

Objectives: To evaluate available data on efficacy/effectiveness and safety of the off-label use of thalidomide in pediatric patients with inflammatory bowel disease (IBD), including CD disease and ulcerative colitis (UC).

Methods: A literature review was conducted using electronic databases PubMed, SciELO, and Embase, with specific keywords and MeSH terms related to thalidomide use in pediatric patients with IBD. Inclusion criteria encompassed randomized clinical trials (RCT), cohort studies, case-control studies, case reports, and case series focusing on pediatric patients with CD or UC from 2001 to 2023. Studies addressing effectiveness, safety outcomes, and adverse events (AE) of thalidomide were considered. Data analysis involved descriptive methods, reporting remission rates, symptom improvement, time to remission, and maintenance of IBD remission. AE frequencies were also reported, referencing the Brazilian manufacturer's package inserts for thalidomide.

Results: The manual selection added three references, resulting in 10 articles eligible for the review. Among these, two were RCT, six were case series, and two were case reports, comprising 213 participants with an age range of five to 16 years old at thalidomide initiation. RCT demonstrated thalidomide's efficacy in inducing and maintaining remission in pediatric patients with refractory CD and UC. Positive responses were also observed in case series, with notable reductions in disease activity scores, corticosteroid doses, and surgical intervention rates. Safety assessments revealed peripheral neuropathy as a significant AE, often leading to treatment discontinuation. Despite varying cumulative doses, neuropathy occurred independently, suggesting a cumulative dose-dependent relationship. Other common AE included constipation, drowsiness, and dermatitis. The safety profile was consistent across RCT, case series, and case reports.

Conclusions: Thalidomide can be considered as an alternative option for pediatric patients with refractory IBD, leading to disease remission. However, monitoring for peripheral neuropathy and potential dose adjustments are necessary. No new or unknown AE related to the medication were identified in this study, emphasizing the need for continuous monitoring and caution in thalidomide use, especially considering its potential for serious AE such as neuropathy.