FRI0478 SEROLOGICAL AUTOIMMUNITY IN PATIENTS WITH RHEUMATIC IMMUNE-RELATED ADVERSE EVENTS: CORRELATION WITH SEVERITY AND TREATMENT
Authors: C. Campochiaro, A. Tomelleri, R. Ferrara, C. Lazzari, G. De Luca, D. Signorelli, A. Bulotta, V. Gregorc, M. Garassino, L. Dagna
Journal: Annals of the Rheumatic Diseases (2020)

Background: Immune checkpoint inhibitors (ICIs) can induce a variety of rheumatic immune-related adverse events (Rh-irAEs). Few data are available on which features can predict the occurrence of long-lasting and severe Rh-irAE Objectives: To describe the serological features associated with long-lasting and severe Rh-irAE. Methods: ICI-treated patients were identified. Patients’ demographics, histotype of cancer, ICI, time interval from ICI start to Rh-irAE onset, characteristics of Rh-irAEs were recorded. Patients were tested for autoimmunity panel (a-IP): RF, ACPA, ANA, anti-SSA, anti-SSB, anti-Sm, anti-RNP, anti-Jo1, ANCA, ASMA, AMA, anti-dsDNA, anti-tireoglobulin, anti-tireoperoxidas, IgM and IgG anti-cardiolipin and anti-β2 glicoprotein I, crioglobulins. All patients were treated with steroids (CS). In case of flare of the Rh-irAE, csDMARDs or bDMARDs were started. Associations between a-IP status and need for DMARD start was evaluated. Non parametric tests were used. Results: 22 Rh-irAE were included (see Table 1). Median age at Rh-irAE onset was 70 (50 – 84) years. 2 patients (9%) had a personal history of psoriasis. Median time from ICI start to Rh-irAE onset was 5 (1 – 26) months. 11 patients (50%) developed 1 Rh-irAE, 10 (45.4%) 2 and 1 (4.5%) 3. The most frequent were arthritis (A, 14, 63.6%), cutaneous vasculitis (CV, 5, 22.7%), PMR-like (4, 18.2%), polymyositis (PM, 4, 18.2%), myocarditis (Myo, 3, 13.6%) and dermatomyositis (DM, 2, 9.1%). Median initial prednisone dose was 25 (10 – 75) mg daily. In 14 patients (63.6%) a csDMARD was started upon steroids tapering. 9 patients (41%) were treated with methotrexate (MTX, 4, 18.2%) with hydroxychloroquine (HCQ, 2, 9.1%) with mycophenolate (MMF, 2, 9.1%) with colchicine (colch). 6 patients were treated with bDMARDs. 3 patients (50%) were treated with anakinra (ANK), 2 (33.3%) with IVIG and 3 (50%) with tocilizumab (TCZ). 13 patients (59.1%) were a-IP+. A significantly higher percentage of a-IP+ patients received DMARDs (11, 84.6%) compared to a-IP- patients (2, 22.2%,p = 0.0007). A significantly higher percentage of a-IP+ patients were treated with bDMARDs (5, 38.5%) compared to a-IP- patients (0, 0%, p = 0.05). We analysed whether in csDMARD-treated patients the need for bDMARDs was higher in a-IP+ but we found no statistical significance (45.4% vs 0%, p = 0.487). Table 1. Characteristics and treatment of Rh-irAEs patients. Age, Sex Cancer ICI Onset (monts ) Rhem-irAE Treatment Response ICI stop AutoAb 1 69, M Lung, adeno Nivo 3 Myo CS, MMF, ANK, TCZ LDA Y, D pANCA 2 70, M Bladder Atezo 1 A, CS, MTX Rem Y, T Neg 3 79, M Lung SCC Pembro 1 A CS Rem No Ro52 4 52, M Lung, LCC Nivo 6 A, CV CS, MTX, ANK, TCZ LDA No ANA 1:160 s 5 82, M Lung, LCC Pembro 3 PMR CS Rem No Neg 6 56, M Melanoma Pembro 26 PMR, PM CS, MTX Death Y, D ANA 1:160 s, pANCA 7 72, M Lung, adeno Pembro 5 A, CV CS, MTX, TCZ HDA (TCZ) Y, T ANA 1:160 s 8 74, M Lung, adeno Pembro 1 PMR CS, MTX LDA No ANA 1:160 s 9 75, M Lung, adeno Pembro 1 PM, Myo CS Rem Y, D Neg 10 75, M Lung, adeno Nivo 9 A CS Rem No Neg 11 68, F Lung, adeno Atezo 18 A CS, MTX LDA Y, T Neg 12 35, M Melanoma Nivo 2 A CS, MTX LDA No ANA 1:640 s 13 79, M Lung, SCC Nivo 15 A, PMR CS, MTX, ANK Death (NR) Y, D Ro52 14 77, M Lung, adeno Pembro 8 DM CS, HCQ, IVIG LDA Y, D ANA 1:320 PCNA 15 67, M Lung, adeno Nivo 13 A CS, MTX LDA No ASMA 16 74, M Lung, SCC Atezo 1 A, CV CS, HCQ, Colch LDA Y, D Neg 17 70, M Lung, adeno Nivo 5 A, CV CS Rem Y, D Neg 18 70, M Lung, adeno Pembro 15 A CS LDA No ASMA 19 69, M Lung, adeno Nivo 5 DM CS, HCQ, MMF, IVIG, Tacro MDA Y, T ANA 1:!60 s 20 84, M H&amp;N, SCC Nivo 3 Ph CS Rem Y, D Neg 21 67, M Lung, adeno Durva 5 A, PM, Myo CS LDA Y, D ANA 1:160 h 22 50, F Lung, LCC Nivo 1 A, CV CS, HCQ Rem Y, D Neg Conclusion: The presence of serological autoimmunity might be helpful in detecting patients with Rh-irAEs refractory to steroid therapy. Disclosure of Interests: Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Alessandro Tomelleri: None declared, Roberto Ferrara: None declared, Chiara Lazzari: None declared, Giacomo De Luca Speakers bureau: SOBI, Novartis, Celgene, Pfizer, MSD, Diego Signorelli: None declared, Alessandra Bulotta: None declared, Vanesa Gregorc: None declared, Marina Garassino: None declared, Lorenzo Dagna Grant/research support from: Abbvie, BMS, Celgene, Janssen, MSD, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, SG, SOBI, Consultant of: Abbvie, Amgen, Biogen, BMS, Celltrion, Novartis, Pfizer, Roche, SG, and SOBI