Checkpoint inhibitor induced colitis

Checkpoint Inhibitor-Induced Colitis is a form of colitis that occurs as an adverse effect of cancer immunotherapy, specifically therapies that involve checkpoint inhibitors. Checkpoint inhibitors are a class of drugs used in the treatment of various cancers. They work by blocking certain proteins made by some types of immune system cells, such as T cells, and some cancer cells. These proteins help keep immune responses in check, and blocking them can boost the immune response against cancer cells. However, this enhanced immune response can sometimes attack the body's own tissues, leading to conditions such as checkpoint inhibitor-induced colitis.

Causes and Mechanism

Checkpoint inhibitor-induced colitis is primarily caused by the administration of checkpoint inhibitors, which include drugs targeting the CTLA-4, PD-1, and PD-L1 pathways. The most commonly implicated drugs are ipilimumab (a CTLA-4 inhibitor), nivolumab, and pembrolizumab (both PD-1 inhibitors). The exact mechanism by which these drugs induce colitis is not fully understood but is believed to involve an exaggerated immune response leading to inflammation of the colon.

Symptoms

The symptoms of checkpoint inhibitor-induced colitis can range from mild to severe and include diarrhea, abdominal pain, blood in the stool, and in severe cases, perforation of the colon. The onset of symptoms typically occurs within weeks to months after starting therapy with checkpoint inhibitors.

Diagnosis

Diagnosis of checkpoint inhibitor-induced colitis involves a combination of clinical evaluation, stool tests to rule out infectious causes, and endoscopic examination of the colon, often with biopsy. Imaging studies such as CT scans may also be used to assess the extent of inflammation and to rule out other causes of symptoms.

Treatment

Treatment of checkpoint inhibitor-induced colitis depends on the severity of symptoms. Mild cases may be managed with symptomatic treatment and temporary cessation of the checkpoint inhibitor therapy. Moderate to severe cases require the administration of corticosteroids to reduce inflammation, and in cases where corticosteroids are ineffective, other immunosuppressive drugs such as infliximab, a TNF-alpha inhibitor, may be used. In severe cases, hospitalization and intravenous steroids may be necessary, and surgery may be required if there is perforation of the colon or if the condition does not respond to medical treatment.

Prevention and Management

Preventive strategies for checkpoint inhibitor-induced colitis include close monitoring of patients for symptoms of colitis during treatment with checkpoint inhibitors and prompt initiation of treatment at the first signs of colitis. Management strategies focus on balancing the need to control cancer with the need to manage the adverse effects of treatment, and may involve dose adjustments or temporary cessation of therapy with checkpoint inhibitors.