The imaging phenotype and long-term outcomes of immune checkpoint inhibitor-induced inflammatory arthritis and arthralgia

Musculoskeletal immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs) are increasingly recognised. While clinically apparent inflammatory arthritis (IA), characterised by joint swelling, is frequently observed, arthralgia occurs at an even higher frequency. Imaging is a valuable tool for delineating arthritis phenotypes; however, data in ICI-IA and ICI-arthralgia remain limited, with most studies restricted to small retrospective cohorts. Early evidence suggests that ICI-IA persists in approximately half of patients, but outcomes in arthralgia alone are less well characterised. Lower-grade irAEs have been associated with improved cancer outcomes, yet no study has directly compared oncological outcomes between patients with ICI-IA and ICI-arthralgia.

This thesis hypothesised that ICI-induced musculoskeletal toxicity represents a spectrum of inflammatory phenotypes with distinct imaging features associated with differing clinical trajectories. This programme of work utilised whole-body MRI (WB-MRI) and ultrasound to define pathoanatomical patterns of inflammation, identify baseline predictors of persistent disease and disease-modifying anti-rheumatic drug (DMARD) requirement, and compare cancer outcomes between ICI-IA and ICI-arthralgia.

A prospective cohort of patients with new musculoskeletal symptoms following immunotherapy underwent baseline imaging and longitudinal follow-up of musculoskeletal and oncological outcomes. A high burden of subclinical inflammation was observed, particularly in patients with arthralgia, alongside diverse inflammatory and structural changes. Three main WB-MRI patterns were identified: polymyalgia rheumatica (PMR), peripheral IA, and a PMR/peripheral IA overlap. Peripheral IA was the most common pattern and was associated with an increased likelihood of persistent disease and DMARD requirement. Patients with ICI-arthralgia were as likely to develop persistent disease as those with ICI-IA; however, patients with IA demonstrated improved overall survival. Multivariable prediction models for disease persistence were developed to support clinical decision-making and guide patient selection for interventional trials. Further work is required to clarify the prognostic significance of subclinical inflammation and to evaluate longitudinal imaging evolution.