Background Immune checkpoint modulation has changed the cancer therapy landscape in recent years . Randomised controlled trials now demonstrate superiority to standard chemotherapy in squamous cell lung cancer, renal cell cancer , squamous cell head and neck cancer  and malignant melanoma . However, blockade of these checkpoints results in a multitude of autoimmune sequelae including joint disease. As these therapies become first-line in oncology, they will likely place a significant burden on rheumatology services.
Objectives To establish the prevalence of rheumatological manifestations of checkpoint blockade in a non-trial standard care setting.
Methods All patients treated with Nivolumab or Ipilimumab (as single agent or in combination) in a standard care setting within a single centre were included and the number of suspected cases with rheumatological manifestations identified from the case records.
Results 75 patients have been treated with Nivolumab single agent and 12 with combination Nivolumab plus Ipilimumab in Oxford over the last 15 months. Within that cohort, there were 7 suspected cases of joint disease giving a potential prevalence of 8%. Of those 7, 2 had confirmed disease requiring therapy, both had received Nivolumab/Ipilimumab combination. Both cases were rheumatoid factor and CCP negative. One case responded to prednisolone only, while the second case was refractory to steroids, methotrexate and infliximab but responded to IL-6 blockade with Tocilizumab.
Conclusions We observed an approximate 8% prevalence of checkpoint mediated autoimmune joint disease within a relatively short follow up period of 15 months. The longer-term prevalence may be higher. Both patients requiring therapy had been exposed to Ipilimumab suggesting the inflammatory joint toxicity with this agent may be higher than that caused by Nivolumab.
Checkpoint immunotherapy is set to become the first-line standard of care in a number of cancers. This will lead to an increased demand for rheumatology services. The rheumatology community needs to develop strategies and trials in order to classify and treat these patients appropriately.
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Disclosure of Interest None declared
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