Mimickers of Immune Checkpoint Inhibitor-induced Inflammatory Arthritis.

The differential diagnosis of inflammatory arthritis as an immune-related adverse event can be challenging as patients with cancer can present with musculoskeletal symptoms that can mimic arthritis because of localized or generalized joint pain. In addition, immune checkpoint inhibitors can exacerbate joint conditions such as crystal-induced arthritis or osteoarthritis, or induce systemic disease that can affect the joints such as sarcoidosis. This distinction is important as the treatment of these conditions can be different from that of immune-related inflammatory arthritis.

[Rheumatic adverse events due to immune checkpoint inhibitors]. / Reumatische klachten door immunotherapie bij kanker.

BACKGROUND: Oncological survival and quality-of-life improved significantly after introduction of immune checkpoint inhibitors (ICIs). Immunotherapy, however, also decreases immunotolerance, potentially inducing autoimmune reactions. This can result in symptoms mimicking rheumatic diseases. CASE DESCRIPTION: Patient A, 51-years-old, female, was treated with adjuvant nivolumab for metastatic melanoma. After 9 months, she developed arthritis. Prednisone 30 mg/ day and methotrexate significantly improved arthritis, followed by prednisone tapering. Patient B, 75-year-old, male with metastatic melanoma treated with Ipilimumab/Nivolumab developed malaise and reduced muscle strength shortly after treatment start. Patient was suspected of myositis/myocarditis, treated with methylprednisolone, which resulted in a rapid improvement. CONCLUSION: ICIs can cause rheumatic adverse events, resulting in decreased quality of life that may require immunesuppressive treatment. Disruption or cessation of ICIs may occur. These adverse events demand low-threshold rheumatological referral and collaboration between oncologist and rheumatologist. Further research must indicate the most effective immunosuppressive therapies with minimized negative oncological impact.

Identification of outcome domains in immune checkpoint inhibitor-induced inflammatory arthritis and polymyalgia rheumatica: A scoping review by the OMERACT irAE working group.

INTRODUCTION: 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 may not be appropriate. We summarized 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 core domain set generation process, we systemically searched Medline (Pubmed), EMBASE, Cochrane, and CINHL through March 2021 to identify all studies that provide both clinical descriptions and domains relevant to ICI-induced IA and ICI-induced PMR. 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, over a third of which utilized non-specific diagnoses of "arthritis," "arthralgia," and/or "PMR". Other publications provided the number, the distribution and/or names of specific joints affected, while others labeled the irAE as the corresponding rheumatic disease, such as rheumatoid arthritis or spondyloarthritis. Most distinct 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 subsequent response, as well as 32 tumor response. CONCLUSION: There is considerable heterogeneity in the domains used to clinically characterize ICI-induced IA and ICI-induced PMR. 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.

Novel positron emission tomography tracers for imaging of rheumatoid arthritis.

Positron emission tomography (PET) is a nuclear imaging modality that relies on visualization of molecular targets in tissues, which is nowadays combined with a structural imaging modality such as computed tomography (CT) or Magnetic Resonance Imaging (MRI) and referred to as hybrid PET imaging. This technique allows to image specific immunological targets in rheumatoid arthritis (RA). Moreover, quantification of the PET signal enables highly sensitive monitoring of therapeutic effects on the molecular target. PET may also aid in stratification of the immuno-phenotype at baseline in order to develop personalized therapy. In this systematic review we will provide an overview of novel PET tracers, investigated in the context of RA, either pre-clinically, or clinically, that specifically visualize immune cells or stromal cells, as well as other factors and processes that contribute to pathology. The potential of these tracers in RA diagnosis, disease monitoring, and prediction of treatment outcome will be discussed. In addition, novel PET tracers established within the field of oncology that may be of use in RA will also be reviewed in order to expand the future opportunities of PET imaging in RA.