THU0615 Immune related adverse events (IRAES) associated with checkpoint inhibitors: 12 cases from a single centre
Authors: D. Ennis, F. To, S. Jamal
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Immune checkpoint inhibitors (ICI) have made a significant impact on the treatment of many advanced malignancies. There is little data on the rheumatologic complications of these treatments. <h3>Objectives</h3> We describe 12 cases of rheumatologic IRAEs following ICI treatment to further characterise the spectrum of disease and treatment responses. <h3>Methods</h3> We report patients evaluated in a general Rheumatology outpatient clinic from 2014 to 2017. Cases were defined as those with new rheumatologic symptoms following treatment with an ICI. Alternative explanations for the presenting syndrome were excluded clinically. Clinical data was extracted by retrospective chart review. <h3>Results</h3> This case series includes 12 patients (6 female, 6 male) with a mean age at IRAE onset of 63.9 years (range 33–79). Multiple cancers were represented including melanoma (n=9), Hodgkin's lymphoma (n=1), squamous cell lung cancer (n=1), and adenocarcinoma of the lung (n=1). 5/12 patients received Nivolumab, 8/12 received Pembrolizumab, and 2/9 received Ipilimumab. ICI exposure was associated with various rheumatologic IRAEs including PMR-like syndrome (n=4), symmetric polyarthritis (n=6), psoriatic arthritis (n=1), oligoarthritis (n=1), and erythema nodosum (n=1). Other IRAEs were also noted including vitiligo (n=1), pulmonary capillaritis (n=1), ulcerative colitis flare (n=1), inflammatory seborrheic keratosis and psoriasis (n=1). The mean time of onset of the IRAE from the first exposure to an ICI was 6.8 months (range 0–21 months). In 7 cases, rheumatologic symptoms worsened with each ICI dose. Laboratory investigations demonstrated elevated CRP in 7 cases (mean 75.6; range 3.7–290.1), RF positivity in 2 cases, weak positive ANAs in 4 cases (1:80), SSA positivity in 2 cases, and a single case where a pre-existing anti-CCP antibody was identified. Steroids were used in 11 cases at a mean starting dose of 36 mg (range 10–50 mg) by mouth daily for an average duration of 6.1 months (range 1–12 months). Other DMARDs were necessary in some cases (Hydroxychloroquine n=1; Methotrexate n=5). While 6 patients experienced rapid improvement, 4 experienced gradual improvement. Most patients achieved partial resolution of symptoms (n=6) while only 4 achieved complete resolution. Tumour response was observed in all 12 patients. <h3>Conclusions</h3> This case series of IRAEs associated with ICI treatment suggest that symmetric polyarthritis and PMR-like syndromes are the most common rheumatologic IRAEs, although the spectrum is broad. IRAEs seem to develop around 6 months after first exposure, worsen with ongoing doses of ICI administration, and respond to treatment with corticosteroids. Treatment doses and duration were higher than expected for phenotype, with few patients achieving significant improvement with short courses. Those with IRAEs tend to have good tumour response, despite concurrent use of immunosuppressants. MTX and HCQ appear to be safe and effective, but more experience with these and other DMARDs/biologics is required in these patients. <h3>Disclosure of Interest</h3> None declared