Cancer immunotherapies, such as immune checkpoint inhibitor (ICI) therapies, harness the power of the body’s own immune system to fight cancer and have greatly improved survival of patients with a wide variety of cancers. Unfortunately, ICI therapy can also activate the immune system to attack healthy tissues and lead to autoimmune and inflammatory diseases as side effects. Johns Hopkins rheumatologists have seen increasingly more patients with inflammatory arthritis after ICI treatment and noticed that the arthritis doesn’t always go away after the patients stop their cancer treatment. This study by the Johns Hopkins Arthritis Center evaluated how many patients with arthritis from cancer immunotherapy continued to have symptoms of inflammatory arthritis after stopping their cancer treatment, in addition to determining what features put patients at greater risk for having persistent arthritis.
Why was this study done?
Cancer immunotherapy can cause side effects called immune-related adverse events (irAEs) due to excess activation of the immune system. Inflammatory arthritis, one of the common irAEs, is increasingly seen by Hopkins rheumatologists who noticed that many patients were not experiencing resolution of their arthritis after their cancer therapy was stopped. The researchers wanted to understand the percentage of patients who had persistent arthritis, how long the arthritis went on after immunotherapy cessation, and which patients were more likely to have persistent arthritis. They also evaluated whether using immunosuppressive treatment for inflammatory arthritis affected the tumor response to ICI therapy.
How was this study done?
Patients were referred to the Johns Hopkins Arthritis Center for inflammatory arthritis after ICI therapy and followed over time (i.e., longitudinally). Symptoms and signs of arthritis as well as the use of medications for inflammatory arthritis were evaluated at each follow-up visit in rheumatology. Additionally, information on cancer status (e.g., whether the cancer had progressed or not) was obtained at each visit. The percentage of patients with persistent arthritis was calculated at 3 months and 6 months after immunotherapy cessation. Statistical models were used to determine factors that influenced whether patients had persistent arthritis.
What were the major findings?
Of the patients that returned for follow-up visits, 70% still had active arthritis 3 months after their cancer immunotherapy was stopped, while 48% had active arthritis after 6 months. Inflammatory arthritis was less likely to improve in those with longer duration of immunotherapy use, in those receiving combination (i.e., more than one) immunotherapy, and in patients with multiple other immune-related adverse events. Tumor response did not appear to be impacted by the immunosuppressive medications used to treat arthritis.
What is the impact of the work?
This was the first study to show widespread persistence of inflammatory arthritis due to cancer immunotherapy and to identify risk factors that can predict arthritis persistence. Importantly, this study suggests that treating the arthritis does not negatively impact the tumor response to ICI immunotherapy. In patients with risk factors for persistence, physicians can do more intense monitoring, make early referrals to rheumatology, and consider more intensive treatment for arthritis.
This research was supported by:
- NIAMS T32 grant
- NIAMS R01 (Ami Shah Co-PI)
Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation. Braaten TJ, Brahmer JR, Forde PM, Le D, Lipson EJ, Naidoo J, Schollenberger M, Zheng L, Bingham Iii CO, Shah AA, Cappelli LC. Ann Rheum Dis. 2019 Sep 20. pii: annrheumdis-2019-216109. doi: 10.1136/annrheumdis-2019-216109. [Epub ahead of print]