**3. Immune-related adverse events (irAEs)**

With the increasing use of ICIs as novel therapies for cancer treatment, it is expected to observe more side effects and adverse events secondary to these medications. The use of ICIs is rising exponentially, with approximately 40% of patients with cancer in the United States in 2019 eligible for treatment [13]. ICIs are not the only medication class to cause adverse effects, as other types of immunotherapies can cause this. With more immunotherapies currently being investigated, the number of available treatments could exponentially increase over time. Despite the observed clinical advantages these medications demonstrate, they produce a myriad of side effects that can involve several body systems. These side effects are called irAEs. The incidence and onset of irAEs vary depending on the class and dose of ICIs, the type of cancer, and factors related to patients [13]. More than two-thirds of reported cases of cancer immunotherapy-related irAEs are related to ICIs, and three drugs (Ipilimumab, Nivolumab, and Pembrolizumab) are responsible for almost 60% of reported cases [14]. It is believed that CTLA-4 might be more closely related to causing irAEs since its mechanism of action is less specific compared to PD-1/PD-L1 medications [10]. The onset of irAEs has been described as occurring as early as within a few days of ICI initiation and ≥ 1 year after completion of therapy. The median onset is within 2–16 weeks from the commencement of therapy [14–16]. Patients treated with combined therapy, anti-PD-1/PD-L1 + anti-CTLA-4 have an increased incidence, severity, and earlier onset of irAEs [13, 14].

The exact mechanism as to why irAEs occur due to ICIs is not entirely understood. It is important to note that there are differences in the clinical presentation and frequency of specific irAEs and the organs most commonly involved [17]. The most frequent irAEs include gastrointestinal, endocrine, and dermatological [18]. **Table 2** shows a full list of all reported irAEs. Uveitis only accounts for approximately 1% of


## *Eye Diseases - Recent Advances, New Perspectives and Therapeutic Options*


*Obtained from Ramos-Casals M, Brahmer JR, Callahan MK, et al. Immune-related adverse events of checkpoint inhibitors. Nat Rev. Dis Prim. 2020;6 (1). doi:10.1038/s41572-020-0160-6.*

**Table 2.**

*Organ-based reported irAEs.*

patients with irAEs. However, it is of utmost importance to be aware of it since delay in diagnosis and treatment could lead to detrimental irreversible visual consequences.

Treatment depends on the organ system affected and the grade of toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE) classification. Specific treatments for irAEs beyond uveitis are out of the scope of this chapter. However, some of the treatments used are glucocorticoids, hormone replacement, immunosuppressive agents, IV immunoglobulin, plasma exchange, and monoclonal antibodies.
