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BackgroundPatients with chronic inflammatory diseases (CID) have an increased risk for contracting infections. For patients with rheumatic diseases EULAR recommends protecting them from vaccine-preventable diseases.ObjectivesTo assess the knowledge and awareness of common vaccinations and extent of immunization among patients with CID in Denmark, Finland, Norway, Sweden (Nordics), and to identify gaps between the existing EULAR vaccination recommendations and current practice as experienced by patients.MethodsA structured anonymous online survey for patients with CID ((rheumatological disease (RD), inflammatory bowel disease (IBD) and dermatological diseases (DD)) was conducted in 2022.The survey was answered by 1748 respondents (1031 patients with RD, 543 with IBD and 563 with DD).ResultsAmong respondents, 89% were female and 58% had disease duration of above 10 years. In total, 56% were treated in specialised and 32% in primary care. Majority had ongoing systemic immunosuppressive treatment (IT) (65%). Majority of RD (59%) and IBD (66%) patients were treated in specialised care whereas minority of DD patients (38%) were treated in specialised care.Forty-nine percent (49%) responded that their healthcare professional (HCP) did not inform them about the increased risk of infection – however, 55% of the respondents believed they are somewhat or much more likely to suffer from infections than those without CID or treatment, 33% thought there is no difference and 13% did not know there is a difference.In total 68% of respondents considered it important to get vaccinated due to CID or IT. The number was particularly high in RD group (74%), although 63% stated they had not received any information regarding vaccinations at the start of their treatment.Commonly recommended vaccinations by the HCP were COVID 19 (66%), influenza (63%) and pneumococcal (45%) vaccination. When comparing respondents ≥65 and <65 years, there was a difference in how often the influenza (71% vs. 57%) and pneumococcal (57% vs. 38%), but not COVID 19 vaccination (68% vs. 65%), were recommended. In addition, 74% and 75% of respondents receiving IT were recommended influenza and COVID 19 vaccination, respectively.In total, 22% had their vaccination status checked before initiating treatment;the lowest percentage was in DD (16%) and the highest in RD (25%). However, 44% of respondents received influenza vaccination before initiation of treatment. Moreover, 62% and 74% of respondents received influenza and COVID 19 vaccination while on treatment, respectively.Eighty-six percent (86%) did not receive a vaccination plan in relation to their CID and treatment. Moreover, 64% of the respondents (RD 57%;DD 71% and IBD 66%) did not have vaccination status assessed on a regular basis. Forty-three percent (43%) were dissatisfied with the follow-up of vaccination status by their HCP. Respondents of age ≥65 years were more satisfied than the younger ones (34% vs. 25% very satisfied) and respondents with RD were more satisfied than those with IBD or DD (33% vs. 25% vs. 20%).Forty-four percent (44%) responded that the information on vaccinations related to their CID and treatment was difficult to find and 71% would like to receive more information.The respondents with RD had different level of awareness regarding EULAR vaccination recommendations. The degree of awareness among patients with RD treated with IT are presented in Figure 1.ConclusionThis Nordic survey provides insights on patients' information needs, information sources and own experiences related to recommendations on vaccinations in relation to their CID and IT. The results confirm a gap between patients' expectations and needs vs. the information they actually receive. Our findings demonstrate a need for increased awareness among patients, providers and HCP regarding EULAR vaccination recommendations in patients with RD.Reference[1]Furer V, et al. 2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis 2020;79: 9–52.Acknowledgements:NIL.Disclosure of InterestsMeliha C Kapetanovic Grant/research support from: Received independent research grants from Roche and Pfizer, Randeep Mandla Shareholder of: Pfizer, Employee of: Current employee of Pfizer Norway, Maria Seddighzadeh Shareholder of: Pfizer, Employee of: Current employee of Pfizer Sweden, Susanne Thiesen Gren Shareholder of: Pfizer, Employee of: Current employee of Pfizer Denmark, Maaria Palmroth Consultant of: Employee of MedEngine Oy and contractor for Pfizer Oy, Employee of: Contractor for Pfizer Oy, Finland, Dan Henrohn Shareholder of: Pfizer, Employee of: Current employee of Pfizer AB, Sweden, Anne Grete Frostrup Shareholder of: Pfizer, Employee of: Current employee of Pfizer Denmark, Anna-Maria Hiltunen Consultant of: Pfizer. Employee of Nordic Healthcare Group, Jussi Ranta Consultant of: Pfizer. Employee of Nordic Healthcare Group, Anna-Kaisa Asikainen Consultant of: Pfizer. Employee of Nordic Healthcare Group, Veli-Jukka Anttila Speakers bureau: Lectures for Pfizer, MSD, Astellas, Roche, GSK, BMS, Biogen, Sandoz, Gilead, Unimedic Pharma, Boehringer-Ingelheim, Astra-Zeneca, Consultant of: Consultant for Pfizer and MSD.
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BackgroundData on serological immunity after three doses and the long-term immunogenicity (persistence) of COVID-19 vaccine in patients with inflammatory rheumatic diseases (IRD) treated with different immunomodulating drugs are still limited.ObjectivesTo elucidate if 1) a third dose COVID-19 vaccine improves antibody responses, compared to two doses, in patients with IRD treated with biologic or targeted synthetic DMARD (b/tsDMARDs) treatment given as monotherapy or in combination with conventional synthetic DMARDs (csDMARDs) compared to controls, and 2) the persistence of antibody response after two doses of COVID-19 vaccine in IRD patients.MethodsAntibody levels to two antigens representing Spike full length protein and Spike S1 and a Nucleocapsid C-terminal fragment (used to confirm previous COVID-19 infection) were measured in serum samples collected 2-12 and 21-40 weeks after the second vaccine dose and 2-12 weeks after the third dose using a multiplex bead-based serology assay. A sufficient antibody response (seropositivity) was defined as having antibodies over the cut-off level for both spike antigens (1). WT (wild type) anti-Spike IgG and omicron BA.1 and BA.2 variants were measured. Patients with IRD receiving immunomodulating treatment, regularly followed at a rheumatology department and a group of controls were recruited from five Swedish region.ResultsIn total, 323 of 414 patients with IRD and 36 controls who received three vaccine doses participated in this part of the study. Following treatment groups were included: rituximab (n=118;68% female;mean age 67 years), abatacept (n=18;72% female;mean age 64 years), IL6r inhibitors (n=60;73% female;mean age 64 years), JAK-inhibitors (n=44;80% female, mean age 52 years), TNF-inhibitors (n=59;70% female;mean age 47 years;), IL12/23/17 inhibitors (n=24;46% female;mean age 54 years) and controls (n=36;75% female, mean age 51 years). b/ts DMARD treatment was given as monotherapy or in combination with csDMARD, methotrexate (MTX) being the most frequently used csDMARD (32.5%). Compared to results after two vaccine doses, proportion (%) of seropositivity after three vaccine doses increased significantly in groups rituximab +/- DMARD (p=0.003 and p=0.004, respectively), IL6r inhibitors +DMARD (p=0.02), and abatacept+DMARD (p=0.01). However, the proportion of seropositivity after three vaccine doses was still significantly lower in rituximab treated patients (52%) compared to other treatment groups or controls (p<0.001) (Figure 1A/B). Antibody response to WT, omicron sBA.1 and sBA.2 showed similar pattern with the lowest levels among patients treated with rituximab.When antibody response was compared between 2-12 weeks and 21-40 weeks after second dose, the proportion of seropositive rituximab treated patients decreased from 34.9 % to 32.6%. All patients with JAK inhibitors and with JAK-inhibitors and IL6r-inhibitors seropositive 21-40 weeks after the second vaccine dose. Patients treated with other bDMARDs were not included in this analysis due to limited number participants.ConclusionIn this Swedish study including IRD patients receiving different b/t DMARDs, a sufficient immunogenicity of the third dose of COVID-19 vaccine was observed in all treatments with exception for rituximab. However, the increased proportion of seropositivity after the third COVID-19 vaccine doses in rituximab and other patients with insufficient response to two doses including response to the omicron variants, supports the current recommendations on additional booster doses. The immunogenicity of two vaccine doses was preserved to 40 weeks in majority of patients treated with different immunomodulating treatment with exception for rituximab.Figure 1.AcknowledgementsThe study has been supported by the independent research grants from Roche.Disclosure of InterestsMartina Frodlund: None declared, Per Nived: None declared, Katerina Chatzidionysiou Consultant of: consultancy fees from Eli Lilly, AbbVie and Pfizer., Grant/research support from: Research grand from Galapagos, Anna ödergren: None declared, Eva Klingberg: None declared, Monika Hansson: None declared, Elisa Pin: None declared, Lars Klareskog: None declared, Meliha C Kapetanovic Grant/research support from: independent research grants från Pfizer and Roche.
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Background: In line with other reports, our group showed that patients treated with rituximab had signifcant impaired antibody response compared to patients treated with other biologic and targeted and synthetic disease modifying anti-rheumatic drugs (csDMARD). Objectives: To investigate predictors of response to COVID-19 vaccination (2 doses of mRNA vaccines, 2 doses of virus vector vaccines or combinations of these) in patients with infammatory rheumatic diseases (IRD) treated with ritux-imab and controls. Methods: Antibody levels to three antigens: Spike protein full length, Spike S1 and Nucleocapsid C-terminal fragment (to confrm previous COVID-19 infection) were measured in sera collected before vaccination and 2-12 weeks after the second vaccine using a multiplex bead-based serology assay. The antigen-specifc cut-off was defned as the median fuorescence intensity signal plus 6x standard deviations across 12 pre-pandemic controls. A good vaccine response was defned as having antibodies over the cut-off level for both spike antigens. Proportion (%) responders was compared between patients and controls (Chi2 test). Patients with IRD receiving last rituximab treatment within a mean (range) 193 (23-501) days before frst vaccination participated. Individuals without IRD served as a control group. Predictors of a good vaccine response were explored using multivariate logistic regression analysis adjusted for age, sex, disease duration, diagnosis (systemic vasculitis/RA/JIA/other), concomitant csDMARD, rituximab dose and prednisolone dose. Hazard ratio (chanse) of a good antibody response in relation to time between the last rituximab treatment and vaccination was studied by Kaplan-Meier survival analysis. Results: In total, 145 patients receiving rituximab and 61 controls were inclyded. Of these, 82 received rituximab as monotherapy (67% women;mean age 66 years, mean disease duration 13 years;33% had RA/JIA and 60% vasculi-tis) and 63 received rituximab+csDMARD (62% women;mean age 66 years;mean disease duration 17 years;76% had RA/JIA and 10 % vasculitis). Controls (n=61) were 74% women and mean age 49 years. Compared to controls, rituximab patients had lower antibody levels for both spike proteins (p<0.001). Proportion (%) responders among patients receiving rituximab as monotherapy (40.2%) and rituximab+DMARDs (25.4%) was signifcantly lower than in controls (98.4%) (p<0.001, Chi2). Higher age, concomitant csDMARD at vaccination and shorter time from last rituximab treatment predicted impaired antibody response (multivariate logistic regression model) (Table 1). Longer time between the last rituximab course and vaccination was associated with better antibody response (Figure 1). Conclusion: Patients with IRD getting vaccinated with two doses of COVID19 vaccine during the treatment with rituximab have the ability to develop antibody response although the response is impaired. For each month passed after the last rituximab course, the chance of good antibody response increases with 30%. Younger patients receiving rituximab as monotherapy and vaccinated preferably several months after the last rituximab treatment have the highest chance of achieving a good antibody response.
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Background: Initial studies on the immunogenicity of COVID-19 vaccines in patients with immune-mediated infammatory 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. Objectives: To 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). Methods: Antibodies against two antigens representing Spike full length protein and Spike S1 and a Nucleocapsid C-terminal fragment (used to confrm 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 classifed as the signal passing an antigen specifc 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 defned 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. Results: In total, 414 patients (320 RA/JIA/psoriatic arthritis/axial spondylar-thritis, 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-inhib-itors (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 signifcantly 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 vascu-litis diagnosis, remained signifcant predictors of antibody response (Table 1). All vaccines were well tolerated. 14 (3.4%) patients reported an increased activity in their IRD following vaccination. Conclusion: In 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 abata-cept should be prioritized for booster doses of COVID19 vaccine.