Background/Purpose: Immune checkpoint inhibitors (ICI), increasingly used cancer therapeutics, can cause off-target inflammatory effects called immune-related adverse events (irAEs), including ICI-induced inflammatory arthritis (ICI-induced IA) and polymyalgia rheumatica (ICI-induced PMR). There are no validated classification criteria or outcome measures for these conditions, and adaptation of treatment recommendations from corresponding rheumatic diseases, such as RA, spondyloarthritis and PMR, may not be appropriate. In this study, we aimed to collate clinical descriptors of ICI-induced IA and ICI-induced PMR and aggregated domains used for these conditions in order to inform the development of a core set ­of outcome domains.

Methods: As the initial step of the OMERACT core domain set generation process, we systemically searched Medline (Pubmed), EMBASE, Cochrane, and CINHL through March 2021 to identify all studies that provided both clinical descriptions and domains relevant to ICI-induced IA and ICI-induced PMR. Publications were sorted into groups based on the clinical characterization of the disease. Outcome domains were mapped to core areas, such as pathophysiological manifestations, life impact, resource use, and longevity/survival, as suggested by the OMERACT 2.1 Filter.

Results: We identified 69 publications (Figure 1) which were sorted into seven groups based on clinical descriptors of arthritis/PMR (Table 1). At least one rheumatologist was a co-author in 41 (59%) publications. Over a third of these publications utilized non-specific clinical diagnoses of “arthritis,” “arthralgia,” and/or “PMR”. Other publications provided the number (n=12 publications), the distribution, size and/or names of specific joints affected (n=17 publications), while others labeled the irAE as the corresponding rheumatic disease, such as rheumatoid arthritis or spondyloarthritis (n=9 publications). Outcomes used for ICI-IA and ICI-PMR are listed in Figure 2. Most distinct outcome domains mapped to the pathophysiology/manifestations core area (24 domains), such as signs/symptoms (13 domains), labs (6 domains), and imaging (5 domains), with harm domains of adverse effects from irAE treatment and fear of irAE treatment decreasing ICI efficacy. Forty-three publications also referenced irAE treatment and 35 publications described the subsequent response. Unique to this population, tumor response was an outcome domain used in 32 publications.

Conclusion: There is considerable heterogeneity in the domains used to clinically characterize ICI-induced IA and ICI-induced PMR. Among outcomes, there were several domains mapped to the pathophysiologic manifestations core area, although several publications highlighted domains evenly distributed among the other core areas of life impact, longevity/survival and resource use. Assembling classification criteria specific to ICI-induced IA and PMR in addition to gaining eventual consensus achievement of core areas and domains are next steps in order to study and effectively treat these conditions.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/identification-of-outcome-domains-in-immune-checkpoint-inhibitor-induced-inflammatory-arthritis-and-polymyalgia-rheumatica-a-scoping-review-by-the-omeract-irae-working-group/