MRI Reveals ICI-Associated Inflammatory Arthritis

Author: By Lynda Williams, Senior medwireNews Reporter

medwireNews: Magnetic resonance imaging (MRI) may aid in the assessment of cancer patients who develop joint pain during immune checkpoint inhibitor (ICI) therapy, indicates preliminary research published in JAMA Network Open. 

Findings from a case series of eight patients with ICI-induced inflammatory arthritis (IIA) “suggest that MRI may be useful for early detection of erosive disease, as well as to help identify patients at high risk for erosive disease, and thus guide medical decision-making regarding management of ICI-IIA”, write Sarthak Gupta, from the National Institutes of Health in Bethesda, Maryland, USA, and co-authors. 

The six women and two men, aged 50–65 years, underwent MRI of the hands, wrists, knees or ankles after developing musculoskeletal symptoms between 1 and 44 weeks after beginning pembrolizumab, avelumab or bintrafusp alfa monotherapy, or nivolumab alone or in combination with ipilimumab. 

Clinical evaluation revealed mild or moderate synovitis or tenosynovitis, considered to be “clinically secondary to inflammatory disease rather than degenerative disease”, the researchers say. Six patients had multiple small joints affected, while one patient showed arthritis in both knees and one wrist, and a second patient had inflammatory arthritis of the knees and ankles. 

MRI revealed tenosynovitis and bone marrow oedema of the small joints, as well as effusion and synovial thickening in the knees and ankles. Three patients showed erosions including one patient who developed ICI-IIA a month after beginning ICI therapy and was also found to have elevated anti-cyclic citrullinated peptide autoantibodies. 

One patient who developed arthritis 4 weeks after beginning nivolumab but persisted with treatment developed erosive disease and fixed joint deformities. She later began bintrafusp alfa therapy, with MRI after 6 months showing persistent synovitis and tenosynovitis but no new or worsening erosions. 

One patient whose rheumatoid arthritis was in remission before beginning ICI therapy developed new onset of pain, although erosions before and after treatment could not be compared. 

Sarthak Gupta et al report that of the six patients who discontinued or paused ICI therapy, one did so after achieving a complete response because of musculoskeletal complications. 

ICI-IIA was managed with nonsteroidal anti-inflammatory drugs or acetaminophen in three patients, with one of the individuals also receiving intra-articular corticosteroids. ICI-IIA resolved completely in five patients given oral prednisone and one patient required methotrexate, while one patient developed serious infection before disease-modifying arthritis therapy could be initiated and another declined systemic therapy. 

The researchers believe MRI could be “an important tool in the assessment of ICI-induced articular symptoms”, and hope that “a prospective study of MRI may be fruitful for understanding the pathophysiological processes and long-term clinical implications of this entity.” 

They continue: “Quantitative measurements through MRI in future studies could potentially help standardize the grading of this adverse event to guide treatment stratification, prevent prolonged exposure to high-dose systemic steroids, and allow early resumption of anticancer therapy.” 

Reference 

Subedi A, Williams SG, Yao L, et al. Use of magnetic resonance imaging to identify immune checkpoint inhibitor-induced inflammatory arthritis. JAMA Netw Open; 3: e200032, published online 26 February 2020. doi:10.1001/jamanetworkopen.2020.0032