Prevalence, therapy and tumour response in patients with rheumatic immune-related adverse events following immune checkpoint inhibitor therapy: a single-centre analysis

Abstract

Background: Immune checkpoint inhibitors (ICIs) improved cancer therapy by inducing a higher immune system activity. This effect can cause rheumatic immune-related adverse events (rh-irAEs), which have not yet been extensively studied. Methods: We analysed 437 patients between 2014 and 2019, treated with ipilimumab (anti-CTLA-4) and/or nivolumab (anti-PD-1) or pembrolizumab (anti-PD-1) at the Clinic for Internal Medicine III, Oncology, Haematology and Rheumatology at the University Hospital Bonn, Germany. Results: Of the 437 patients 60% were males. Patients were mainly treated for melanoma, lung cancer, head and neck tumour and urothelial carcinoma. At least one immune-related adverse event (irAE) was observed in 163 patients (37.3%), including rh-irAE. Most common side effects were rash, colitis and hepatitis. We identified 19 patients (4.3%) with a minimum of one rh-irAE due to ICI therapy; three of those had a pre-existing rheumatic disease. Arthralgia developed most frequently in eight patients (42.1%). Other rh-irAEs were: arthritis ( n = 7; distinguished in rheumatoid arthritis, psoriatic arthritis, juvenile idiopathic arthritis and undifferentiated arthritis), myalgia ( n = 2) and myositis ( n = 3). Most rh-irAEs were classified as moderately severe (Common Terminology Criteria of Adverse Events grade 2: 68.4%). Median time between starting ICI therapy and the occurrence of rh-irAE was 109 days (interquartile range 40–420 days). Fifteen patients (78.9%) were treated with glucocorticosteroids. In four cases additional therapy with methotrexate or tocilizumab was required. Even though patients benefited from ICI treatment, therapy had to be discontinued in six of the participants due to rh-irAE. Interestingly, patients with rh-irAE had a significantly higher tumour response compared with patients without rh-irAE (94.4% versus 43.5%; p < 0.0001). Conclusion: Rh-irAEs occur under ICI therapy, especially in patients with higher tumour response. However, they are not the most frequent irAE after ICI exposure: 9.3% of all irAEs were rheumatic (20 rh-irAE cases in 19 patients of a total of 215 irAE cases in 163 patients).

Rheumatoid Arthritis Symptoms Diagnosed by Rheumatic Immune-related Adverse Events Caused by Nivolumab in a Patient with Esophageal Cancer

“…rh-irAEs include rheumatoid-like symptoms and rheumatic diseases, such as arthralgia, myalgia, arthritis, and tendinitis. However, symptoms of arthralgia and myalgia account for the majority of reports, and reports of the development of RF and anti-CCP-positive rheumatoid arthritis, as in this case, are rare (6)(7)(8). Patients with pre-existing autoimmune diseases (ADs) are largely ex-cluded from clinical trials of ICIs (9,10).…”

Co-Inhibitory Molecules – Their Role in Health and Autoimmunity; Highlighted by Immune Related Adverse Events

“…A blurred picture is starting to emerge, where we see a tendency for CTLA-4 blockade to induce gut affection more often than blockade of the PD-1 pathway. By contrast, PD-1 and LAG-3 blockade more often result in pneumonitis and joint affection ( 119 ).…”

Construction of an immune-related lncRNA signature pair for predicting oncologic outcomes and the sensitivity of drugs to treat adverse reactions to immunotherapy in lung adenocarcinoma

“…Methotrexate sensitivity was higher in the high-risk group, whereas the parthenolide and rapamycin sensitivity was lower in the high-risk group. Methotrexate is usually used for autoimmune disease therapy, and a single-center analysis reported that methotrexate has a good curative effect in rheumatic ir AEs (10). Parthenolide is one of the biologicals that play an anti-in ammatory role by inhibiting nuclear factor kappa B (NF-κB) and cytokine tumor necrosis factor (TNF)-α (37,38).…”

“…Furthermore, ir AEs may even lead to systemic infections and death, and an increase in fatal events has been reported (9). Corticosteroid therapy can successfully treat most ir AEs, but a combination of immunosuppressors is needed to combat more serious adverse reactions (10,11). However, since it is unclear whether a patient can undergo immunosuppressive therapy of ir AEs safely, there is an urgent need to nd some biomarkers to predict the drug sensitivity of immunosuppressors.…”