Pos1563 arthritis phenotype following check point inhibition is unspecific and seronegative in most patients – results from the prospective observational rimra study

Background Patients with rheumatic immune related adverse events (irAEs) after cancer therapy with immune check point inhibitors represent a new challenge for rheumatologists. The incidence of irAEs is expected to increase and more knowledge about pathogenesis, disease course and treatment response is needed. The ongoing RIMRA (Rheumatic Immune Related Adverse events in patients treated with check point inhibitors) study aims to describe clinical presentation, disease course and outcome of rheumatic irAEs in patients treated with immune check point inhibitors. Objectives To describe baseline characteristics and treatment of arthritis patients included in the RIMRA cohort. Methods RIMRA is an ongoing prospective, observational study including adult patients with de novo symptoms of rheumatic disease or flare of established rheumatic disease after > 1 dose of treatment with immune check point inhibitor. Eligible patients who are referred to Rheumatology departments at Diakonhjemmet Hospital, (DH), Oslo University Hospital Rikshospitalet (RH), University Hospital of North Norway (UNN), Ålesund Hospital (ÅH) and Hospital of Southern Norway (HSN) are asked to participate in the study. Clinical and biochemical data as well as blood samples for biobanking, are collected at study visits at baseline and after 3,6 and 12 months. Patients are treated at the discretion of the treating rheumatologist in collaboration with the oncologist. Results Between August 2018 and January 2023 56 patients have been included at 4 centers (DH, UNN, ÅH, HSN). 49 patients had de novo disease and 7 patients had flare of preexisting rheumatic disease (RA n=5, PsA n=2). Polyarthritis was the dominant phenotype in 45% of the patients followed by oligoarthritis and monoarthritis (Figure 1). Joint distribution was heterogenic. 7 patients were positive for RF/anti-CCP, of whom 5 had preexisting RA. Disease characteristics at baseline are presented in Table 1. The mean Clinical Disease Activity Index (CDAI) score was 18, corresponding to a level of moderate disease activity. Throughout the study period anti-rheumatic treatment has been given to the following proportions of patients: i.a steroid injection:45%, prednisolone: 71%, methotrexate: 30%, anti-TNF: 21%, tocilizumab: 1,7%, sekukinumab: 1,7 %, ustekinumab: 1,7%, leflunomide: 1,7%, apremilast: 1,7%. Death has been registered in 13 (23%) patients, of whom 10 patients had received prednisolone, 3 patients had received methotrexate and 1 patient had received anti-TNF treatment. Table 1. Demographics/baseline characteristics N=56 Age (y ) 65 (12) Women n (% ) 33 (59) Cancer diagnosis n (% ) Melanoma Lung cancer Urothelial/renal cancer Hodgkin lymphoma Laryngeal cancer MPNST Colon cancer 30 (56) 11 (21) 6 (11) 2 (3,5) 1 (,1,8) 1 (1,8) 1 (1,8) Check point inhibitor n (% ) Anti-CTLA-4 Anti-PD1/PDL-1 CTLA-4 and PD1/PD-L1 PD1+LAG-3 CTLA-4 and PD-1 and PD1+LAG-3 0 (0) 35 (67) 15 (29) 1 (1,9) 1 (1,9) Preexisting rheumatic disease n (% ) Psoriatic arthritis Seronegative RA Seropositive RA 2 (3,5) 1 (1,8) 4 (7) CTCAE grade n (% ) G1 G2 G3-4 15 (28) 24 (44) 15 (28) Anti-CCP/RF positive n (% ) 7 (13) ESR mm/h 35 (29) CRP mg/L 30 (40) SJC (66 joints ) 5 (7) TJC (68 joints ) 5 (8) Physician global VAS mm (0-100 ) 36 (26) Patient global VAS mm (0-100 ) 53 (24) CDAI 18 (15) Values are mean (SD), if not otherwise indicated. Figure 1. Conclusion Most patients with rheumatic immune related adverse events in the RIMRA study have seronegative inflammatory arthritis with no specific arthritis pattern/phenotype. The disease activity varies, but is on average moderately high upon referral to rheumatologist, as reflected in both CDAI and CTCAE grading at baseline. Most patients need anti-rheumatic treatment. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests Marte Heiberg Speakers bureau: Dr Heiberg has received a speakers honorarium from Roche, Silje Watterdal Syversen: None declared, Karen Irgens: None declared, Helle Bitter: None declared, Gunnstein Bakland: None declared, Marta Nyakas Speakers bureau: Personal fees for lectures and expert meetings from BMS, Novartis, MSD and Pierre Fabre, Hanne Ødegård: None declared, Hanne Vestaby: None declared, Inger-Lise Knutsen: None declared, Kjetil Bergsmark: None declared, Espen A Haavardsholm Speakers bureau: Dr Haavardsholm has received personal fees from Pfizer, AbbVie, Celgene, Novartis, Janssen, Gilead, Lilly and UCB outside of the submitted work., Maria D Mjaavatten: None declared.