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New anti-cancer therapeutics have been developed in the recent years and dramatically change prognosis and patient management. Either used alone or in combination, immune checkpoint inhibitors (ICI), such as anti-CTLA-4 and anti-PD1/PD-(L)1, act by removing T-cell inhibition to enhance their antitumor response. This change in therapeutic targets leads to a break in immune-tolerance and a unique toxicity profile resulting in immune complications. These side effects, called Immune-Related Adverse Events (IrAEs), can affect all organs, with a wide range of clinical and biological presentations and severity. Various rheumatic and musculoskeletal manifestations have been reported in the literature, ranging from mild arthralgia, polymyalgia rheumatica, to genuine serodefined rheumatoid arthritis and myositis. Tolerance studies suggest some correlations between IrAEs occurrence and tumor response. Assessment of patient musculoskeletal status prior to the start of the ICI is warranted. Management of rheumatic IrAEs does not usually request ICI discontinuation, exception for myositis or very severe forms where it should be discussed. Treatment relies on non-steroidal anti-inflammatory drugs (NSAIDs) or low dose glucocortioids (

Vaccination is considered as a cornerstone of the management of COVID-19 pandemic. However, while vaccines provide a robust protection in immunocompetent individuals, the immunogenicity in patients with inflammatory rheumatic diseases (IRD) is not well established.A monocentric observational study evaluated the immunogenicity of a two-dose regimen vaccine in adult patients with IRD (n=123) treated with targeted or biological therapies. Serum IgG antibody levels against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike proteins were measured after the second vaccination. In addition, a search for observational studies performed in IRD under biologic or targeted therapies up to September 31, 2021 (PROSPERO registration number: CRD42021259410) was undertaken in publication databases, preprint servers, and grey literature sources. Studies that reported sample size, study date, location, and seroprevalence estimate were included. A meta-analysis was conducted to identify demographic differences in the prevalence of SARS-CoV-2 antibodies.Of 123 patients (median age 66 IQR 57-75), 69.9% have seroconverted after vaccination. Seroconverted patients were older than non-seroconverted ones in our cohort. Rituximab was associated with a significantly low antibody response. Besides, we identified 20 seroprevalence studies in addition to our cohort including 4423 participants in 11 countries. Meta-analysis confirmed a negative impact of rituximab on seroconversion rate and suggested a less substantial effect of abatacept, leflunomide and methotrexate.Rituximab impairs serological response to SARS-CoV-2 vaccines in patients with IRD. This work suggests also a negative impact of abatacept, methotrexate or leflunomide especially when associated to biological therapy.

International audience; BACKGROUND:Epstein-Barr Virus (EBV) is a widely disseminated lymphotropic herpes virus implicated in benign and malignant disorders. In transplant patients, immunosuppressive drugs (cyclosporine) diminish control of EBV replication, potentially leading to lymphoproliferative disorders (LPD). Rheumatoid arthritis (RA) patients have impaired control of EBV infection and have EBV load ten times higher than controls. As post transplant patients, patients with RA have increased risk of developing lymphomas. Immunosuppressive drugs used to treat RA (conventional disease modifying drugs cDMARDs or biologics bDMARDs) could enhance the risk of developing LPD in RA patients. We have previously shown that long term treatment with Methotrexate and/or TNF alpha antagonists does not increase EBV load in RA. Our objective was to monitor the Epstein-Barr Virus load in RA patients treated with Abatacept (CTLA4 Ig), a T cell coactivation inhibitor, and Tocilizumab, an anti IL6 receptor antibody.METHODS:EBV load in the peripheral blood mononuclear cells (PBMCs) of 55 patients under Abatacept (in 34% associated with Methotrexate) and 35 patients under Tocilizumab (in 37% associated with Methotrexate) was monitored for durations ranging from 6 months to 3 years by real time PCR. The influences of treatment duration and disease activity score 28 (DAS28) index on EBV load were analyzed.RESULTS:Abatacept did not significantly modify EBV load over time. Tocilizumab significantly diminished EBV load over time. No patient (of 90) developed EBV associated lymphoma.CONCLUSION:Long term treatment with Abatacept or Tocilizumab does not increase EBV load in the PBMNCs of patients with RA.

Background Epstein-Barr Virus (EBV) is a widely disseminated lymphotrophic herpes virus implicated in a lot of benign and malignant disorders. In transplant patients, EBV load is enhanced because of immunosuppressive drugs (cyclosporine) and in a few cases, it can lead to lymphoproliferative disorders (LPD). An EBV load higher than 500 copies per 500 ng of DNA is a predictive factor of post transplant lymphoma [1,2] Similarly, immunity against EBV is particular in RA patients: the level of antibodies against EBV is higher in RA than in healthy controls [3], RA patients have a defective EBV specific supressor T cell function [4].The risk to develop a lymphoma is higher in RA patients than in controls. We have previously shown that: 1/ EBV load is 10 fold higher in RA patients than in controls [5] and 2/ Methotrexate and TNF alpha antagonists (immunosuppressive drugs used in RA patients) do not increase EBV load in RA [6]. Objectives Here, we monitored EBV load over 3 years in patients with RA treated by 2 more recent biologics, Abatacept (CTLA4 Ig) a T cell activation inhibitor, or Tocilizumab, an anti IL6 receptor antibody. Methods EBV load in the peripheral blood mononuclear cells (PBMCs) from 55 patients under Abatacept (+/− Methotrexate) and 35 patients under Tocilizumab (+/− Methotrexate) was monitored from 6 months up to 3 years, by real time PCR. The influences of treatment duration and disease activity score 28 (DAS28) index on EBV load were analyzed. Results Neither Abatacept nor Tocilizumab significantly enhanced EBV load over time. None of our patients developed EBV associated lymphoma. Conclusions Long term usage of Methotrexate with Abatacept or Tocilizumab in patients with RA does not significantly influence EBV load in PBMCs. References Baldanti F et al. High levels of Epstein Barr virus DNA in blood of solid organ transplant recipients and their value in predicting postransplant lymphoproliferative disorders. Journal of Clinical Microbiology 38: 613–619, 2000 Morito M,et al. Quantitative analysis of Epstein Barr virus load by using a real time PCR assay. Journal of Clinical Microbiology 37: 132–136, 1999 Alspaugh M et al. Elevated levels of antibodies to Epstein Barr virus antigens in sera and synovial fluids of patients with rheumatoid arthritis. Journal of Clinical Investigation 67: 1134–1140, 1981 Tosato G et al. Defective EBV specific suppressor T cell function in rheumatoid arthritis. New England Journal of Medicine 305: 1238–1243, 1981 Balandraud N et al. Epstein-Barr Virus Load in the peripheral blood of patients with Rheumatoid arthritis. accurate quantification using re[2] Kimura H, al time Polymerase chain reaction. Arthritis and Rheumatism 2003;48:1223–1228. Balandraud N et al. Long-term treatment with methotrexate or tumor necrosis factor alpha inhibitors does not increase epstein-barr virus load in patients with rheumatoid arthritis. Arthritis and Rheumatism 57(5): 762–767, 2007 Acknowledgement This work was supported by AORC AP-HM, INSERM and Chugai. Disclosure of Interest E. Massy: None declared, O. Muis-Pistor: None declared, M. Martin: None declared, I. Auger: None declared, M.-C. Guzian: None declared, S. Guis: None declared, J. Roudier: None declared, T. Pham: None declared, N. Balandraud Grant/research support from: This work has been partially supported by Chugai group