Immune checkpoint inhibitor colitis is condition where there is an inflammation of the colon that can occur as a side effect of immune checkpoint inhibitor therapy. These drugs, such as pembrolizumab, nivolumab, and ipilimumab, are used to treat various cancers by enhancing the immune system’s ability to recognise and destroy cancer cells. However, in some cases, these drugs can cause the immune system to mistakenly attack healthy tissue, including the gastrointestinal tract, leading to colitis.

Why Does Immune Checkpoint Inhibitor Colitis Happen?

Immune checkpoint inhibitors work by blocking the proteins (CTLA-4, PD-1, and PD-L1) that prevent the immune system from attacking cancer cells. While effective in combating cancer, these drugs can also disrupt normal immune regulation and cause an overactive immune response against the gut’s own cells. This results in inflammation and damage to the colon. The exact mechanism is still being studied, but genetic predisposition, exposure to these drugs, and pre-existing autoimmune conditions may increase the risk of developing colitis.

When Does Immune Checkpoint Inhibitor Colitis Occur?

Colitis can occur at any time during treatment with immune checkpoint inhibitors but is more commonly observed within the first few weeks to months of therapy. The risk is higher with certain combinations of drugs, such as the combination of nivolumab and ipilimumab. Patients who have pre-existing inflammatory bowel disease (IBD) may be at greater risk of developing colitis while on these therapies.

How to Treat Immune Checkpoint Inhibitor Colitis

Treatment for immune checkpoint inhibitor colitis typically involves the following approaches:

1. Discontinuing the immunotherapy: If colitis is suspected, it is crucial to halt the use of the immune checkpoint inhibitors to prevent further damage and to allow the immune system to recover. This decision should be made in consultation with the healthcare provider, as discontinuing treatment may impact the overall management of the cancer.
2. Corticosteroids:
   • First-line treatment: High-dose corticosteroids (e.g., prednisone or methylprednisolone) are often used to reduce inflammation and control symptoms. These drugs work by suppressing the immune response that is attacking the gut.
   • Duration of treatment: The duration of corticosteroid treatment varies, but it is usually tapered gradually to prevent withdrawal symptoms and recurrence of symptoms.
3. Immune-modulating therapies:
   • In severe cases of colitis that do not respond to corticosteroids, other immunosuppressive drugs such as infliximab or cyclosporine may be used.
   • Thiopurines (e.g., azathioprine, mercaptopurine) and methotrexate may also be considered as alternative therapies for patients who do not respond to corticosteroids.
4. Symptomatic treatment:
   • Anti-diarrhoeal medications (e.g., loperamide) can help control diarrhoea associated with colitis.
   • Hydration and electrolyte balance: It is important to maintain hydration and electrolyte balance due to fluid loss from frequent bowel movements.
5. Regular monitoring:
   • Frequent follow-up visits: Patients receiving immune checkpoint inhibitors should be monitored regularly for signs of colitis, especially if they develop gastrointestinal symptoms such as abdominal pain, diarrhoea, or blood in stool.
   • Endoscopic evaluation: In some cases, colonoscopy or flexible sigmoidoscopy may be used to assess the extent of colitis and to rule out other causes of gastrointestinal symptoms.

Other Resources:

• https://www.webmd.com/cancer/how_immune_checkpoint_inhibitors_treat_cancer
• https://pubmed.ncbi.nlm.nih.gov/28540478/
• https://pmc.ncbi.nlm.nih.gov/articles/PMC6397821/
• https://en.wikipedia.org/wiki/Checkpoint_inhibitor_induced_colitis