O41. PEMBROLIZUMAB THERAPY–INDUCED INFLAMMATORY ARTHROPATHY

Abstract

Background: We present a 69-year-old woman with no personal or family history of inflammatory arthritis who was diagnosed with epithelioid pleural mesothelioma. She failed to respond to cisplatin and Pemetrexed followed by 3 phase I trial agents. She was then treated with Pembrolizumab, an immune checkpoint inhibitor targeting the programmed death-1 (PD-1) pathway, which prevents natural inhibition of T cells and is effective against renal cell carcinoma, lymphoma and melanoma. She responded rapidly and the mesothelioma regressed. Within 48 hours of the first infusion she developed symmetrical pain and stiffness in the small joints of her hands, wrists and elbows, followed by knees, ankles and feet. Severity rapidly escalated and within days she was unable to walk or turn in bed due to pain. Treatment with NSAIDs and paracetamol were ineffective. Methods: On examination there was crepitus of the wrist extensors and hind foot tendons. There was also puffiness of the hands but minimal synovial swelling. Many joints were painful through passive movements. Ultrasound of the MCP, PIP and wrists showed synovial hypertrophy (GS) of 17/22 joints, grade 2 in 4 and grade 1 in 13, and power Doppler (PD) grade 1 in 5 joints. The wrist extensor tendons were both GS grade 1, and PD grade 1 on one side only. The knees were GS grade 1 with normal PD signal and the hind feet joints and tendons were all normal. Blood tests showed raised inflammatory markers (CRP 41, ESR 66), normocytic anaemia and weakly positive rheumatoid factor, but ACPA, ANA, ENA were negative. Results: She started treatment with a tapering schedule of prednisolone starting at 30mg. This was very effective and at 6 weeks she was mostly pain free with a return to normal physical function. Once steroids were weaned, and despite pembrolizumab being on hold, her arthritis rapidly flared again. Conclusion: Several case reports have described inflammatory disease following immune checkpoint inhibitor (ICI) therapy. By inhibiting natural suppression of T cell activation (CTLA4 or PD-1 pathways) a range of autoimmune sequelae are described including most commonly a maculopapular rash, colitis, pneumonitis, hepatitis and thyroiditis. Arthritis can present in either a typical RA pattern or an oligoarthropathy, and a sicca syndrome has been described. Our case was characteristic in demonstrating severe pain, as well as tendon crepitus, a particularly striking and unusual feature. As in our case, ultrasound findings tend to be modest but erosions have been described, and antibodies are either absent or weakly positive. Many cases demonstrate good response to high dose prednisolone, but often relapse once weaned, in which case anti-TNF therapies are reported to be beneficial.