# Sonographic Signatures of Immune Checkpoint Inhibitor-Associated Musculoskeletal Adverse Events

## TL;DR

This study shows that musculoskeletal ultrasound is useful for diagnosing and managing joint-related side effects from cancer immunotherapy.

## Contribution

The study introduces a novel scoring system for ultrasound findings and demonstrates its clinical impact on treatment decisions.

## Key findings

- MSKUS detected inflammation in 74% of patients with ICI-related joint symptoms.
- Ultrasound findings led to treatment changes in 70% of cases.
- MSKUS identified chronic inflammation that had been previously missed in some patients.

## Abstract

Immune checkpoint inhibitors (ICIs), though effective for cancer treatment, can cause immune-related side effects such as inflammatory arthritis (IA) and polymyalgia rheumatica (PMR). This study examined musculoskeletal ultrasound (MSKUS) findings in patients with these ICI-related joint symptoms (MSK-irAEs). Among the 23 patients studied, 83% were diagnosed with MSK-irAEs, and 74% had ultrasound evidence of inflammation. Ultrasound findings led to treatment changes in 70% of cases and helped detect chronic inflammation, which had sometimes been missed for years. Additionally, MSKUS identified other causes of symptoms, supporting ICI continuation in some patients. This study concludes that MSKUS is valuable for both diagnosing and managing ICI-related musculoskeletal issues.

Background: Immune checkpoint inhibitors (ICIs) transformed cancer treatment, producing significant survival benefits. However, ICIs can trigger toxicities called immune-related adverse events (irAEs), including inflammatory arthritis (IA) and polymyalgia rheumatica (PMR)-like syndromes. Our study aimed to systematically further characterize musculoskeletal ultrasound (MSKUS) findings in patients with ICI-IA and ICI-PMR, collectively referred to as “MSK-irAEs”, and explore the role of US in guiding treatment. Methods: The authors conducted a comprehensive chart review for patients receiving ICIs undergoing MSKUS at our center’s rheumatology clinics. US examinations were performed and reviewed by two MSKUS-certified rheumatologists. Descriptive statistics were performed to summarize demographic, clinical, and treatment-related variables. US findings were categorized with a novel scoring system: 0—no signs of inflammatory arthropathy or tendinopathy, 1—potential signs of inflammation (grayscale ≥ 2, effusion without power Doppler, synovial hypertrophy in the joint), and 2—active inflammation in joints and/or tendons (characterized by power Doppler) and signs of inflammation. Results: Twenty-three patients were included. The median age was 63 years, 52% were male, and 87% were White. Melanoma was the most common cancer (48%). MSK-irAEs were diagnosed in nineteen (83%), with MSKUS showing inflammation in seventeen (74%). Sixteen (70%) received escalation in MSK-irAE treatment after MSKUS. Four (17%) had erosive disease due to MSK-irAEs, while one had erosive osteoarthritis. Individuals with inflammatory erosive changes experienced prolonged intervals between symptom onset and MSKUS, ranging from 17 to 82 months, suggesting that erosions may reflect chronic, under-recognized inflammation. On MSK-irAE therapy, nine (47%) experienced symptomatic improvement, five (26%) achieved resolution, and in four (21%) cases, it was too early to assess the response. MSKUS detected other causes of MSK symptoms besides MSK-irAEs in several patients, allowing ICI resumption in one. Conclusions: Our study highlights the clinical utility of MSKUS not only as a diagnostic tool but also to guide therapeutic decision-making.