Do Autoimmune Diseases Impact Side Effect Risk During Immunotherapy Treatment?  

Immune checkpoint inhibitors (ICIs) are a class of medications that have shifted how doctors treat cancer. These drugs work by turning on the body's own immune system to help it recognize and eliminate cancer cells. While this treatment can lead to long-lasting positive responses and improve survival rates, it also carries risks.

When the immune system is activated by these drugs, it can sometimes mistakenly attack healthy organs. This causes side effects known as immune-related adverse events (irAEs). 

For patients with an autoimmune disease—like rheumatoid arthritis, lupus, or thyroid issues—the risk might be higher. Researchers conducted a large-scale data study using medical records spanning from 2014 to 2023. The results were presented at an American Society of Clinical Oncology (ASCO) Annual Meeting.

What is an autoimmune disease?

An autoimmune disease occurs when the human immune system mistakenly identifies healthy tissues and cells as foreign material. Under typical conditions, the immune system distinguishes between the body's own structures and outside elements; however, in autoimmune conditions, this internal recognition process fails. As a result, the immune system generates proteins that bind to specific organs, muscles, or joints, leading to sustained inflammation and functional changes over time. Depending on which area of the body is affected, symptoms can vary widely from persistent fatigue and joint stiffness to broader organ dysfunction. Although the precise triggers usually involve a complex mix of genetics and environmental factors, current management strategies focus on rebalancing immune activity and relieving chronic discomfort.

Opening more treatment options for people with autoimmune diseases

Historically, patients who already have an autoimmune disease—like rheumatoid arthritis, lupus, or thyroid issues—were left out of clinical trials for immunotherapy. Drug developers worried that activating the immune system might trigger severe complications. 

Researchers conducted a large-scale data study using medical records spanning from 2014 to 2023. The results were presented at an American Society of Clinical Oncology (ASCO) Annual Meeting.

The study included adults who had both cancer and a preexisting autoimmune disease. The researchers then carefully matched patients into pairs to directly compare the risk of developing entirely new immune-related side effects. Then the researchers compared patients starting immunotherapies versus those starting traditional chemotherapy or targeted therapies.

Immunotherapy does carry a significantly higher risk, but how?

The study included thousands of matched patient pairs and found that immunotherapy does carry a significantly higher risk of triggering new immune side effects than other options. Specifically, these new side effects affected parts of the body completely separate from the patient's original autoimmune condition.

The data revealed several important findings:

• People taking an immune checkpoint inhibitor were 1.71 times more likely to develop a new immune side effect than those on chemotherapy. They were also 1.43 times more likely to experience these side effects than patients on targeted therapies. This higher risk remained consistent regardless of the patient's age or sex.

• Medications known as CTLA-4 inhibitors carried the highest risk of all. Using a combination of different immunotherapies was the next highest risk group.

• The risk levels changed depending on the type of cancer being treated. People with liver cancer experienced the highest rate of new immune side effects, followed closely by patients with breast cancer.

• People who had preexisting endocrine (hormone-related) autoimmune diseases consistently showed the highest risk of developing new side effects across all comparisons.

Can I get immunotherapy treatment if I have an autoimmune disease?

The study demonstrates that using immune checkpoint inhibitors in patients with a history of autoimmune disease leads to a higher rate of new immune-related side effects compared to chemotherapy or targeted therapies. However, because the risk levels vary drastically based on the specific drug used, the type of cancer, and the patient's original autoimmune condition, doctors should not avoid these drugs entirely. Instead, the findings highlight the absolute necessity for healthcare teams to perform an individualized risk assessment and provide close, personalized monitoring for every patient.

What to do if you have an autoimmune disease and have been recently diagnosed with cancer

If you have a preexisting autoimmune disease and are preparing to start cancer treatment, consider these practical steps:

• Make sure your oncologist has a complete list of any conditions you have been diagnosed with in the past, even if they are currently well-controlled or inactive.

• Don’t be afraid to ask your oncologist as many questions as you need. Ask how the specific class of cancer drug you are prescribed interacts with your particular type of autoimmune disease.

• Keep in mind you may need to be extra aware of side effects. Know exactly which new symptoms to look out for and who to contact immediately if you notice changes in how you feel.

Source: Risk of immune-related adverse events from checkpoint inhibitors in cancer patients with autoimmune disease: An emulated target trial.