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Case history

Image not available. A 65-year-old woman with a history of seronegative arthritis presented to her rheumatology follow-up with night sweats, lethargy, lower back pain and discomfort when lying down. Her medical history included cutaneous melanoma, hypertension and hypercholesterolaemia. A superficial, spreading non-ulcerated 1.2 mm (pT2a) malignant melanoma had been excised from her left thigh 28 years earlier. Her arthritis was well controlled with hydroxychloroquine only. A CT scan revealed metastatic lesions in the retroperitoneum, left external iliac nodes and pelvic sidewalls. Biopsies confirmed recurrence of a BRAF V600E mutant melanoma. Her performance status was 0. Detailed discussions took place with the patient about the risks and benefits of starting immunotherapy vs serine/threonine-protein kinase B-Raf (BRAF)-targeted therapy. The patient decided to proceed with primary treatment with pembrolizumab 200 mg/kg every 3 weeks.

After cycle 1 she experienced grade 2 arthritis and required treatment with prednisolone 30 mg once daily tapered over 4 weeks. A partial response to treatment was confirmed by CT scan 12 weeks after starting treatment. She continued to experience grades 1–2 exacerbations of her arthritis throughout her treatment course, requiring intermittent steroid dosing. Ultimately, she was kept on a maintenance dose of prednisolone 10 mg once daily, which controlled her arthritis symptoms. She was later diagnosed with osteoporosis plus sacral stress fractures and was started on bisphosphonates. She has currently completed 31 cycles of pembrolizumab, with no treatment deferrals. Follow-up CT scans continue to demonstrate response to immunotherapy.

What is the evidence for the safety of immune checkpoint inhibitors (ICPIs) in patients with pre-existing autoimmune disease?

Do patients with pre-existing autoimmune disease have a poorer clinical outcome with anti- programmed cell death protein 1 (PD-1) therapy?

What are the treatment options for our patient's flare of arthritis?

Can we predict which patients are likely to have severe exacerbations of their autoimmune disease?

How should at-risk patients be managed by the multidisciplinary team?

What is the evidence for the safety of ICPIs in patients with pre-existing autoimmune disease?

Clinical trials of immunotherapy have excluded patients with pre-existing autoimmune disease, owing to the potential risk of severe exacerbations related to immune activation. Currently, there are only a small number of retrospective studies detailing the use of immunotherapy in these settings.13

Johnson et al.1 carried out an international multicentre retrospective study of 30 patients with advanced melanoma and pre-existing autoimmune disease receiving ipilimumab. The median age of the patients was 59.5 years (range 30–80 years) and 26 (87%) had stage IV M1c disease. Prior to ipilimumab treatment, 13 patients (43%) were receiving active systemic treatment for their autoimmune disease. Eight patients (27%) had grades 3–5 exacerbations requiring systemic steroids and 10 patients (33%) experienced a new immune-related adverse event (irAE). The duration to autoimmune disease exacerbation was most common between weeks 2 and 3 and at week 6 (range 3 days to 7 months). One patient died from autoimmune colitis ...

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