OP0276 CLINICAL PATTERNS AND FOLLOW-UP OF INFLAMMATORY ARTHRITIS AND OTHER IMMUNE-RELATED ADVERSE EVENTS INDUCED BY CHECKPOINT INHIBITORS. A MULTICENTER STUDY
Authors: J. A. Gómez-Puerta, C. Perez-Garcia, D. Lobo Prat, R. Gumucio, F. Ojeda, A. M. Millán Arciniegas, S. Rodriguez Garcia, V. Ruiz, H. Corominas
Journal: Annals of the Rheumatic Diseases (2020)

Background: Immune checkpoint inhibitors (ICI), such as anti-CTLA-4and anti-PD1/PD-L1 monoclonal antibodies, have produced impressive clinical results in different types of cancer. However, immune-related adverse events (irAEs) may develop a wide spectrum of disabling syndromes. Knowledge of different rheumatic irAEs induced by ICI is increasing over the last years, however clinical patterns, time to onset of different irAEs according to treatment and follow-up are less well known. Objectives: To describe different clinical patterns of rheumatic irAEs induced by ICI and their rheumatic and oncologic outcomes. Methods: We included consecutive patients with rheumatic irAEs from 3 different referral centers in Barcelona with special emphasis in articular irAEs. Four main clinical syndromes were identified: inflammatory arthritis (IA), non-inflammatory arthralgias (NIA), psoriatic arthritis (PsA)-like and polymialgia (PMR)-like. We conducted a baseline visit and then follow-up in order to determine their clinical pattern, treatment response and outcome. Longitudinal visits were done from January 2017 to January 2020. Patients with other non–articular diagnosis were not included in the follow-up analysis. Results: We included 55 patients. A total of 34 patients were male (61.8%) with a mean age of 65.0 ± 11.4 years. Oncologic underlying diagnosis was lung carcinoma in 24 (43.6%) patients, followed by melanoma in 17 (29%), urothelial cancer in 4 (7.3%), breast in 2 (3.6%) and 2 (3.6%) acute myeloid leukemia among others. Seven (12.7%) patients received ICI as combined therapy. Different ICI were used including: Pembrolizumab in 21 (38.2%), Nivolumab 13 (23.6 %), Atezolizumab 6 (10.9%), Nivolumab + ipilimumab 5 (9.0%), Durvalumab 3 (5.5%), Pembrolizumab + epacadostat in 2 (3.6%), 2 anti TIM3, Atezolizumab+ Ibatasertib, Avelumab and Ipilimumab in one case each. 12 out of 55 patients had an underlying rheumatic disease before ICI treatment. Eleven patients developed other irAEs before or at the same time as rheumatic syndromes (mainly colitis and thyroiditis). Main rheumatic irAE included: IA in 23 (41.8%), NIA in 16 (29.1%), PsA-like in 6 (10.9%), PMR-like in 5 (9.1%) among others. Time from ICI to irAEs was 8.3 ± 8.4 months(mo). irAE presented earlier in patients with combined ICI therapy than in patients with monotherapy (6.5 ± 4.0 vs 8.6 ± 8.9 mo, p=NS, Figure 1A). Time (in mo) from ICI initiation to irAE onset was different according to treatments. For Nivolumab 10.0 ± 10.6, Anti TIM3 10.0 ± 1.4, Durvalumab 9.0 ± 2.0, Ipilimumab 7.98 ± 9.21, Pembrolizumab 7.28 ± 7.53, Avelumab 6.0 and Atezolizumab 4.4 ± 5.38 mo (Figure 1B). Time from ICI initiation and onset also differs among rheumatic irAEs (Figure 2). Mean time follow-up was 13.4 ± 10.9 mo. At the last visit, 45% were under GC, mean dose of 3.6 mg/d (range 0-40). DMARD were needed in 15% of patients (6 patients MTX, 1 with LEF and 1 SFZ). At the last visit, 11 (22.9%) patients remain with persistent arthritis, 25% intermittent flares and 52% had a self-limited pattern. Regarding oncologic outcome, 30.2% were on remission, 30.2% in partial response and 39.6% with tumor progression. Eleven (20%) of patients died. Conclusion: We described different clinical patterns according treatment and irAEs. Combined ICI therapy and patients treated with Atezolizumab had earlier onset of symptoms. Vasculitis and PMR-like syndromes appear in earlier phases. After a mean follow-up of around 1 year, one-quarter of the patients remain with persistent arthritis and 15% require DMARD therapy. Disclosure of Interests: Jose A. Gómez-Puerta Speakers bureau: Abbvie, BMS, GSK, Lilly, Pfizer, Roche, Carolina Perez-Garcia: None declared, David Lobo Prat: None declared, Roberto Gumucio: None declared, Fabiola Ojeda: None declared, Ana Milena Millán Arciniegas: None declared, Sebastian Rodriguez Garcia: None declared, Virginia Ruiz Speakers bureau: Lilly, Pfizer, Héctor Corominas Speakers bureau: Abbvie, Lilly, Pfizer, Roche