Inflammatory gastrointestinal diseases associated with PD-1 blockade antibodies

Area of Science:

• Oncology
• Immunology
• Gastroenterology

Background:

• Immune checkpoint blockade agents, such as anti-PD-1, demonstrate clinical efficacy in cancer treatment.
• However, these agents are associated with immune-related adverse events (irAEs) that can impede their development.
• Gastrointestinal irAEs (GI-irAEs) are a significant concern in patients receiving anti-PD-1 therapy.

Purpose of the Study:

• To characterize the incidence, clinical presentation, and outcomes of gastrointestinal immune-related adverse events (GI-irAEs).
• To investigate GI-irAEs specifically in cancer patients treated with anti-PD-1 antibodies.
• To compare the frequency and nature of GI-irAEs with those observed with anti-CTLA-4 therapy.

Main Methods:

• A retrospective study of adult patients with suspected GI-irAEs from anti-PD-1 therapy between 2013 and 2016.
• Patient data were collected via a pharmacovigilance registry and reviewed by a multidisciplinary team.
• Descriptive statistics were used, with quantitative variables presented as median (range) and qualitative variables as frequency (percentage).

Main Results:

• Twenty out of 44 investigated patients (1.5% incidence) had confirmed GI-irAEs related to anti-PD-1 treatment, occurring a median of 4.2 months after initiation.
• The primary symptoms included diarrhea (80%), abdominal pain (65%), and nausea/vomiting (55%).
• The main diagnoses were acute colitis (40%), microscopic colitis (35%), and upper GI inflammation (20%), with corticosteroid response rates ranging from 57% to 87.5%.

Conclusions:

• GI-irAEs associated with anti-PD-1 therapy appear to be less frequent and distinct in presentation compared to those seen with anti-CTLA-4 agents.
• Acute colitis and microscopic colitis are significant GI-irAEs under anti-PD-1 treatment, with varying responses to corticosteroids.
• Further research is warranted to fully understand and manage these events.