Background/Purpose: An altered immune tolerance disturbed by immune checkpoint inhibitors (ICIs) may contribute to new-onset polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) in treated cancer patients. This systematic literature review (SLR) and meta-analysis synthesizes data on the characteristics of ICI-induced PMR and GCA, including pooled prevalence, demographic patterns, clinical features, and treatment-related outcomes. The aim is to present a large-scale meta-analysis offering insights into these syndromes and their potential differences from idiopathic forms.

Methods: The SLR analyzed Medline and EMBASE databases up to July 2024, comparing ICI-induced PMR and GCA to their primary forms. For studies without direct comparisons, SLRs or large observational studies provided the data on primary PMR and GCA. A meta-analysis pooled prevalence, demographics, clinical features, and treatment outcomes when sufficient data were available.

Results: From 1,237 abstracts, 46 were included, yielding 358 patients (314 with ICI-PMR and 44 with ICI-GCA). ICI-PMR had a pooled prevalence of 0.3% [95% CI: 0.1%–1.2%] among ICI recipients. Patients were predominantly males (64% [95% CI: 54%–73%]), with a mean age of 71 years [95% CI: 68–74]. PD1/PDL1 blockers were used in 85% [95% CI: 80%–89%] of cases. Inflammatory pain in the girdles was universal (100%), however pelvic girdle involvement was explicitly reported in only 3 studies. Peripheral arthritis in ICI-PMR was present in 26% [95% CI: 9%–54%], and normal inflammatory markers were detected in 26% [95% CI: 15%–40%]. Glucocorticoids (GCs) completely improved symptoms in 83% of patients [95% CI: 66%–92%], with 13% [95% CI: 12%–34%] requiring DMARDs and 18% [95% CI: 9%–33%] experiencing relapses (Figure 1). Two comparative studies explored differences between ICI vs primary PMR. Vermeulen et al suggested milder symptoms and better outcomes in ICI-PMR (Figure 1) while Fremont et al more frequent peripheral arthritis and higher DMARD use in the ICI group. However, the latter was a brief report with methodological limitations, warranting cautious interpretation.ICI-GCA prevalence was 0.06% among ICI recipients. Male patients comprised 51% [95% CI: 36%–66%], with a mean age of 71 years [95% CI: 68–74]. About 50% [95% CI: 23%–77%] received anti-CTLA4 blockers (alone or with PD1 blockers), while the rest received PD1/PDL1 blockers. Clinical features included cephalic symptoms (85% [95% CI: 70%–93%]), permanent visual loss (23% [95% CI: 12%–39%]), and large-vessel involvement (62% [95% CI: 40%–80%]). High-dose GCs permitted remission in 95% [95% CI: 73%–99%], though 19% [95% CI: 7%–41%] experienced relapses and 10% [2% – 31%] required DMARDs (Figure 1).

Conclusion: ICI-induced PMR and GCA may have distinct clinical profiles than idiopathic forms, potentially with milder symptoms and better treatment responses. Large observational data and meta-analyses on primary forms suggest higher relapse rates and prolonged GC use [1,2], yet further robust comparative studies are needed to validate whether ICI-induced syndromes truly represent a distinct and less severe clinical entity. References[1] Floris A et al. Clin Rheumatol. 2022 [2] Moreel L et al. Joint Bone Spine. 2023

Figure 1. Forest plots related to the main outcomes and clinical features in ICI-PMR (upper panel) and ICI-GCA (lower panel)

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/polymyalgia-rheumatica-and-giant-cell-arteritis-induced-by-immune-checkpoint-inhibitors-a-systematic-review-and-meta-analysis-highlighting-differences-with-the-idiopathic-forms/