What are the rheumatologic adverse events from Immune checkpoint inhibitors?

Immune checkpoint inhibitors such as ipilimumab (targeting CTLA-4), nivolumab, pembrolizumab, cemiplimab (targeting PD-1), and atezolizumab, avelumab, and durvalumab (targeting PD-L1) are powerful immunotherapy drugs used to treat various cancers. By boosting the immune system's ability to recognize and destroy cancer cells, these drugs offer significant therapeutic benefits. However, they can also lead to side effects as the immune system may attack healthy tissues.

The most frequent rheumatologic side effects of Immune checkpoint inhibitors include:

  • Arthralgia (Joint pain): This is a common side effect, with patients often experiencing pain in the hands, knees, shoulders, and other joints. It may or may not be accompanied by visible joint swelling.
  • Inflammatory Arthritis: This resembles conditions such as rheumatoid arthritis, with swelling, warmth, and stiffness, especially in the morning. Symptoms can range from mild to severe and often affect multiple joints.
  • Myositis (Muscle inflammation): Patients may experience muscle pain, tenderness, and weakness, which can be particularly concerning if it interferes with basic functions like standing or lifting objects.

Polymyalgia rheumatica-like symptoms: These symptoms include pain and stiffness in the shoulders, neck, and hips, often affecting daily activities like getting out of bed or standing up from a seated position.

Vasculitis (inflammation of blood vessels): This is a less common but serious side effect where blood vessels become inflamed, potentially leading to symptoms in various organs or tissues.

Sicca Syndrome (dryness of eyes and mouth): Also known as "dryness syndrome," this can affect the mucous membranes, leading to dry eyes and mouth, which may increase the risk of infections or dental issues.


These side effects arise from the very mechanism that makes Immune checkpoint inhibitors effective against cancer. Immune checkpoint inhibitors block immune checkpoints—specifically proteins like CTLA-4, PD-1, and PD-L1—which usually act as brakes on the immune system, preventing it from attacking normal tissues. By blocking these checkpoints, Immune checkpoint inhibitors enhance the immune system’s ability to attack cancer cells but can also cause the immune system to mistakenly target healthy cells, including those in joints, muscles, and connective tissues. This autoimmune-like activity results in inflammation and pain in the rheumatologic system.