FRI0035 INFLAMMATORY ARTHRITIS INDUCED BY IMMUNE-CHECKPOINT INHIBITORS: RESULTS FROM A COMBINED RHEUMATOLOGY/ONCOLOGY OUTPATIENT CLINIC
Authors: Fulvia Ceccarelli, Andrea Botticelli, Alain Gelibter, Ilaria Leccese, Ilaria Zizzari, Grazia Sirgiovanni, Francesca Romana DI Pietro, Ramona Lucchetti, Carlo Perricone, Enrico Cortesi, Marianna Nuti, Fabrizio Conti, Paolo Marchetti, Guido Valesini
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Immune checkpoint inhibitors (ICIs) has radically changed the oncology field: the blockade of co-stimulatory molecules on T cells, antigen presenting cells and tumor cells induces unchecked T cell activation with subsequent immune response targeting malignant cells. In the last years, different ICIs have been approved for the treatment of several malignancies. The stimulation of the immune response could be associated with the development of immune-related adverse events (irAEs), potentially involving every organ/system (1). Musculo-skeletal manifestations represent one of the most common irAEs developing during ICIs treatment: up to 40% of treated patients could experience arthralgia or arthritis. Moving from these evidences, the role of the rheumatologist became very important in the management of ICIs treated patients (2). <h3>Objectives:</h3> To determine the frequency of musculo-skeletal manifestations in patients treated with ICIs in a combined rheumatology/oncology outpatient clinic. <h3>Methods:</h3> From January 2015 we organised a rheumatology/oncology combined outpatient clinic: all patients starting an ICIs treatment were referred from oncologist to rheumatologist. Data from patients, including demographic features, date of diagnosis, comorbidities and previous and concomitant medications, smoke habit, were collected and registered into a standardized, computerized, electronically filled-in form. All the patients underwent to a physical and laboratory evaluation in order to assess the presence of tender and swollen joints. In case of joint involvement, we assessed disease activity by clinimetric evaluation (DAS28) and ultrasonographic assessment of involved joints (presence of active synovitis as for presence of power Doppler). Moreover, a laboratory evaluation including, ESR, CRP, and autoantibodies (ANA, ACPA, RF) was performed. <h3>Results:</h3> Seventy-two patients were evaluated (M/F 48/24, median age 66.0 years, IQR 13.0; median disease duration 7 months, IQR 13.0). Concerning malignant disease, 75.1% were affected by non-small cell lung cancer, 15.3% by renal cell carcinoma, 6.9% by melanoma, 2.7% by other malignancies; all patients were treated with anti-PD-1, 67 (93.1%) with nivolumab and 5 (6.9%) with pembrolizumab. During ICIs treatment, 7 patients (9.7%) developed clinically evident synovitis (absolute risk: 0.1; incidence rate 0.01 patients/month): table 1 reports the main features of these 7 patients. According with ACR/EULAR 2010 criteria, two patients could be classified as affected by rheumatoid arthritis (RA). Six patients (85.7%) were treated by prednisone (dosage range 10-12.5mg/daily) or NSAIDs, experiencing a rapid, complete and persistent response. Patient 2, due to resistance to prednisone, was treated by methotrexate 10mg/weekly achieving remission after 6 weeks. <h3>Conclusion:</h3> The present study represents the first attempt to apply a multidisciplinary approach involving rheumatologists and oncologists in the evaluation of patients treated with ICIs. We found a high absolute risk (10%) to develop synovitis in patients treated by ICIs. Interestingly, the majority of these patients experienced a clinically evident synovitis promptly responding to glucocorticoids and not requiring further DMARDs treatment. This could suggest a peculiar pathogenesis of such ICIs-induced arthritis. <h3>References:</h3> [1] Calabrese L &amp; Velcheti V, Ann Rheum Diseases 2016; 2. Mooradian MJ et al, Semin Arthritis Rheum 2018 <h3>Disclosure of Interests:</h3> Fulvia Ceccarelli: None declared, Andrea Botticelli: None declared, Alain Gelibter: None declared, Ilaria Leccese: None declared, Ilaria Zizzari: None declared, Grazia Sirgiovanni: None declared, Francesca Romana Di Pietro: None declared, Ramona Lucchetti: None declared, Carlo Perricone Speakers bureau: BMS; Lilly, Celgene, Sanofi, Enrico Cortesi: None declared, Marianna Nuti: None declared, fabrizio conti: None declared, Paolo Marchetti: None declared, Guido Valesini: None declared