Background/Purpose: Immune check point inhibitors (ICIs) boost the patient’s immune system by blocking intrinsic down-regulators of immunity by signaling through cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1), or programmed cell death ligand 1 (PD-L1) (1). The resulting hyperactivity of effector T cells may decrease the progression of cancers but increase the risk for autoimmune inflammation termed immune related adverse events (IRAE). Patients on ICIs are at risk of developing such reactions, however, it’s unclear if patients with underlying autoimmune conditions or underlying positive serology are at higher risk.

Methods: This study was based on retrospective analysis of electronic medical records (EMR) of 1,699 patients who received more than one ICI infusion at Upstate University Hospital between 2011 and 2021. We evaluated the clinical characteristics of new and flaring rheumatic and systemic IRAEs documented among patients with or without a prior history of autoimmune disease. This study was performed as a quality improvement project to promote the early recognition of IRAEs in the future. Statistical analysis was performed with chi-square or Fisher’s exact test using GraphPad version 8.0 software. Two-tailed p < 0.05 was considered significant.

Results: Table 1 outlines the baseline characteristics and IRAE of 1699 ICI-treated patients. Table 2 outlines the prevalence of each IRAE in individual patients with prior history of autoimmune diseases. The most common IRAE was pneumonitis followed by thyroiditis, rash, colitis, polyarthralgia, and inflammatory arthritis, respectively. 269 of 1699 patients had preexisting autoimmune disease. 24 potential IRAE were reported, 3 IRAE were analyzed (inflammatory arthritis, polyarthralgia and rash). There were 49 total patients who developed inflammatory arthritis as an IRAE from ICI use, 14 (29%) had underlying autoimmune disease. Having an autoimmune disease conferred a 2.2-fold increased risk for flare of inflammatory arthritis (p=0.013; Table 3). There were 59 total patients who developed polyarthralgia as an IRAE from ICI use, 11 (11%) had underlying autoimmune disease. Having an autoimmune disease was not a risk factor for increased polyarthralgia as an IRAE (p-value =0.5; Table 3). There were 91 patients who developed rash as an IRAE from ICI use, 8 (9%) had underlying autoimmune disease. Having an autoimmune disease was not a risk factor for flare of rash as an IRAE (p-value =0.110; Table 3). 118 autoantibodies were found among the 1699 patients who received ICI. Having positive autoantibodies conferred a 10x-fold increased risk for flare from an IRAE (p< 0.0001; Table 3).

Conclusion: Patients with autoimmune disease were more likely to flare with inflammatory arthritis as an IRAE (2.2-fold increased risk, p-value=0.013; Table 3). Patients with positive autoantibodies were more likely suffer an IRAE compared to individuals with negative autoantibodies (10-fold increased risk, p-value < 0.0001; Table 3). It is critical that patients with underlying autoimmune disease and those with circulating autoantibodies be carefully monitored for possible IRAE during ICI use. Larger cohort studies are needed.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/immune-related-adverse-events-in-checkpoint-inhibitor-treated-cancer-patients-increased-in-patients-with-underlying-autoimmune-disease-and-positive-autoantibodies/