Colitis is a general term for inflammation of the colon, the largest part of the large intestine. This inflammation can cause a range of digestive symptoms. While many conditions can lead to an inflamed colon, it can also arise as a side effect of specific medical therapies. When induced by these treatments, the cause is not an infection but a reaction to a medication designed to interact with the body’s immune system.
Understanding Immunotherapy-Induced Colitis
Immunotherapy is a significant advance in cancer treatment, but its mechanism can lead to side effects like colitis. These treatments, particularly immune checkpoint inhibitors (ICIs), work by disrupting signals that cancer cells use to hide from the immune system. Immune checkpoints normally prevent the immune system from becoming overactive. Drugs targeting checkpoints like CTLA-4 and PD-1 release the brakes on the body’s T-cells, allowing them to recognize and attack malignant cells.
This enhanced immune response, while effective against tumors, can cause the immune system to lose its ability to distinguish between cancer and healthy tissue. When this occurs in the gastrointestinal tract, T-cells can infiltrate the lining of the colon, leading to inflammation. The resulting condition is called immunotherapy-induced colitis (io-colitis) or immune-mediated colitis.
The incidence and timing of colitis can vary based on the specific checkpoint inhibitor used. Therapies targeting CTLA-4, such as ipilimumab, have a higher frequency of causing colitis compared to those targeting PD-1/PD-L1, like nivolumab or pembrolizumab. Combination therapies can lead to an earlier and more severe onset of colitis. The median onset is five to seven weeks after starting treatment, but it can appear as early as one week or months after the therapy has concluded.
Recognizing the Symptoms
The symptoms of io-colitis are a direct result of inflammation in the colon. The most common sign is diarrhea, characterized by an increase in the frequency and a change in the consistency of bowel movements. Patients may experience four or more stools above their baseline in a day. Other symptoms include abdominal pain, blood or mucus in the stool, fever, fatigue, and weight loss.
It is important for any patient undergoing immunotherapy to monitor for these signs. The onset of new or worsening abdominal symptoms, especially acute diarrhea, should be reported to their oncology team without delay. Early communication and intervention can prevent the inflammation from becoming more severe.
The Diagnostic Process
When a patient on immunotherapy reports symptoms of colitis, the medical team begins a process to confirm the diagnosis. The first step involves ruling out other potential causes. Stool studies are ordered to check for infectious agents, including bacteria like Clostridioides difficile, as an infection requires a different treatment approach.
Alongside stool tests, blood tests are performed to look for general markers of inflammation. A stool analysis for fecal calprotectin or lactoferrin may also be used, as these proteins are released by white blood cells in the gut when inflammation is present. These lab tests provide clues but are not specific enough on their own to confirm io-colitis.
The definitive diagnostic tool is an endoscopic evaluation, such as a sigmoidoscopy or a full colonoscopy. During this procedure, the physician can directly see the extent of the inflammation, which might appear as redness, swelling, or ulcers. To confirm the diagnosis, small tissue samples, or biopsies, are taken from the colon lining for a pathologist to examine for the characteristic features of io-colitis.
Treatment and Management Strategies
The management of immunotherapy-induced colitis is tailored to the condition’s severity, graded on a scale from 1 (mild) to 4 (severe). For mild (Grade 1) colitis, initial treatment is conservative. This involves temporarily holding the immunotherapy and providing supportive care, which includes hydration and anti-diarrheal medications like loperamide.
If symptoms are more significant (Grade 2), the checkpoint inhibitor therapy is paused. Systemic corticosteroids, such as prednisone, are prescribed to suppress the inflammation. The goal is to reduce symptoms, after which the steroids are slowly tapered over several weeks. In some instances, an enteric-coated steroid like budesonide, which targets the gut more directly, might be used first.
For severe or steroid-refractory colitis, where inflammation does not respond to corticosteroids, more powerful immunosuppressive drugs are required. Biologic therapies used for inflammatory bowel disease, such as infliximab or vedolizumab, are often administered. These medications can be effective at controlling severe inflammation and preventing complications like colon perforation. Throughout treatment, dietary modifications, like a low-fiber diet, may be recommended to manage symptoms.