Frequency and distribution of various rheumatic disorders associated with checkpoint inhibitor therapy

Abstract

Immune checkpoint inhibitors have advanced the treatment paradigm of various cancers, achieving remarkable survival benefits. However, a myriad of immune-related adverse events (irAE) has been recognized in almost every organ system, presumably because of persistent immune system activation. Rheumatic symptoms such as arthralgia or myalgia are very common. More specific irAE are increasingly being reported. The most frequent ones are inflammatory arthritis, polymyalgia-like syndromes, myositis and sicca manifestations. These rheumatic irAE can develop in ∼5–10% of patients treated with immune checkpoint inhibitors, although true incidence rates cannot be estimated given the lack of prospective cohort studies, and likely underreporting of rheumatic irAE in oncology trials. In this review, we will provide a summary of the epidemiologic data reported for these rheumatic irAE, until more robust prospective longitudinal studies become available to further define the true incidence rate of rheumatic irAE in patients receiving these novel cancer therapies.

Rheumatic Manifestations in Patients Treated with Immune Checkpoint Inhibitors

“…However, a minority of patients develop more pronounced pain with inflammatory features, such as morning stiffness as well as joint swelling suggestive of arthritis. Arthritis prevalence does not seem to exceed 7% [9]. Terminology and heterogeneity issues exist, making estimation of true prevalence difficult.…”

“…Median time to symptom onset following ICI initiation did not exceed the period of three months. Review of the literature, however, highlights the clinical variability of ICI-exposed patients developing arthritis [9,13]. In a recent review of case reports and case series [14], 90 cases of de novo ICI-related arthritis were identified in a period of 18 months.…”

“…On the other hand, a de novo condition with features of myopathy/myositis has been described in recent years following ICI therapy in cancer patients [6,9,13]. The differentiation between paraneoplastic and ICI-induced myositis can be sometimes difficult [35].…”

“…Several case series of patients with ICI-induced sicca [20,30] have been reported. A recent review identified 17 cases of sicca symptoms following ICI treatment [9]. These patients had a median age of 63 years, with a slight male predominance (53%); most had melanoma (71%) and had received anti-PD(L)1 therapy (88%).…”

Integrating the immune microenvironment of prostate cancer induced bone disease

“…The impact of immunotherapy on the bone of patients with PCa has only begun to be explored. It is well established that immune checkpoint inhibitors result in immune‐related rheumatic and musculoskeletal adverse events, such as inflammatory arthritis, arthralgia, and myalgia 77,78 . Yet only recently has a study found that immunotherapies result in SREs.…”