THE IMPACT OF IMMUNOMODULATING TREATMENT ON THE IMMUNOGENICITY OF COVID-19 VACCINES IN PATIENTS WITH IMMUNE-MEDIATED INFLAMMATORY RHEUMATIC DISEASES COMPARED TO HEALTHY CONTROLS. A SWEDISH NATIONWIDE STUDY (COVID19-REUMA)

• Initial studies on the immunogenicity of COVID-19 vaccines in patients with immune-mediated inflammatory rheumatic diseases (IRD) reported diminished antibody response in general, and particularly when treated with rituximab or abatacept (1). Additional data are needed, especially for patients with IRD and immunomodulatory treatments.ObjectivesTo elucidate the antibody response after two doses of COVID-19 vaccine in patients with IRD treated with biologic or targeted synthetic disease modifying anti-rheumatic drugs (b/ts DMARDs) as monotherapy or combined with conventional synthetic DMARDS (csDMARDs).MethodsAntibodies against two antigens representing Spike full length protein and Spike S1 and a Nucleocapsid C-terminal fragment (used to confirm previously COVID-19 infection) were measured in serum obtained before and after the second vaccination using a multiplex bead-based serology assay (2). Patients with IRD receiving immunomodulating treatment, followed at a rheumatology department and healthy individuals (controls) were recruited from five Swedish regions. Antibody positivity was classified as the signal passing an antigen specific cutoff based on the mean intensity signal of 12 selected negative pre-pandemic controls plus 6SD for Spike/S1 and 12SD for Nucleocapsid-C. Good vaccine response was defined as having antibodies over cut-off level for both spike antigens. Percentage of responders in each treatment group was compared to controls (Chi2 test). Predictors of antibody response were determined using logistic regression analysis.ResultsIn total, 414 patients (320 RA/JIA/psoriatic arthritis/axial spondylarthritis, 60 systemic vasculitis and 32 other IRD) and 61 controls participated. Patients receiving rituximab (n=145; 65% female; mean age 65years), abatacept (n=21; 77% female; mean age 66 years), IL6 inhibitors (n=77; 74% female; mean age 64years), JAK-inhibitors (n=58; 75% female, mean age 53years), TNF-inhibitors (n=68; 66% female; mean age 44years;), IL17 inhibitors (n=42; 54% female; mean age 44years) and controls (n=61; 74% female, mean age 49years) were studied. Patients receiving IL6 inhibitor (81.0%), abatacept (43.8%) or rituximab (33.8%) had a significantly lower antibody response rate compared to controls (98.4%), further pronounced if combined with csDMARD (p<0.001) (Figure 1). In the adjusted logistic regression analysis, higher age, rituximab, abatacept, concomitant csDMARD but not IL6 inhibitors, concomitant prednisolone, or a vasculitis diagnosis, remained significant predictors of antibody response (Table 1). All vaccines were well tolerated. 14 (3.4%) patients reported an increased activity in their IRD following vaccination.ConclusionIn this nationwide study including IRD patients receiving b/ts DMARDs a decreased immunogenicity of COVID-19 vaccines was observed in patients receiving rituximab, abatacept and to some extent IL-6 inhibitors. Concomitant csDMARD gave further attenuation. Patients on rituximab and abatacept should be prioritized for booster doses of COVID19 vaccine.References[1]Jena, et al. Response to SARS-CoV-2 vaccination in immune mediated inflammatory diseases: Systematic rev./meta-analysis. Autoim. Rev: 2021;102927[2]Hober, et al. Systematic evaluation of SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serol. C-19 assay. Clin Transl Im. 2021;10(7): e1312Table 1.Predictors of antibody response to COVID-19 vaccineRituximab-1.799<0.0010.170.07-0.42Abatacept-1.9710.0010.140.04-0.45IL6 inhibitor0.0230.9651.020.36-2.94Age (years)-0.0810.0000.920.89-0.96csDMARD-1.1270.0020.320.16-0.66Prednisolone (mg/day)-0.0640.2060.940.85-1.04Frequency (%) of individuals with good antibody response to COVID-19 vaccineAcknowledgementsUnrestricted research grants have been received från Roche and starting grants from the Swedish Rheumatism AssociationDisclosure of InterestsMartina Frodlund Consultant of: Consultancy fees from AstraZeneca and GSK, Katerina Chatzidionysiou Consultant of: Consultancy fees from Eli Lilly, AbbVie and Pfizer, Anna Södergren: None declared, Eva Klingberg: None declared, Anders Bengtsson: None declared, Lars Klareskog Grant/research support from: Research grants from Pfizer, BMS, Affibody, Sonoma Biotherapeutics, Meliha C Kapetanovic: None declared

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