ABSTRACT
BackgroundImpaired immunogenicity of COVID-19 vaccinations in inflammatory arthritis (IA) patients results in diminished immunity. However, optimal booster vaccination regimens are still unknown, due to unstudied kinetics of the immune response after booster vaccinations.ObjectivesThis study aimed to assess the kinetics of humoral and cellular responses in IA patients after the COVID-19 booster.MethodsIn 29 IA patients and 16 healthy controls (HC) humoral responses (level of IgG antibodies) and cellular responses (IFN-γ production) were assessed before (T0), after 4 weeks (T1), and after more than 6 months (T2) from the booster vaccination with BNT162b2.ResultsIA patients, but not HC, showed lower anti-S-IgG concentration and IGRA fold change at T2 compared to T1 (p=0.026 and p=0.031). Furthermore, in IA patients the level of cellular response at T2 returned to the pre-booster level (T0). All immunomodulatory drugs, except IL-6 and IL-17 inhibitors for the humoral and IL-17 inhibitors for the cellular response, impaired the immunogenicity of the booster dose at T2. However, none of the immunomodulatory drugs affected the kinetics of both humoral and cellular responses (measured as the difference between response rates at T1 and T2).ConclusionOur study showed impaired kinetics of both humoral and cellular responses after the booster dose of the COVID-19 vaccine in IA patients, which, in the case of cellular response, did not allow the vaccination effect to be maintained for more than 6 months. Repetitive vaccination with subsequent booster doses seems to be necessary for IA patients.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
ABSTRACT
BackgroundUpadacitinib (UPA) is an oral JAK inhibitor (JAKi) approved for the treatment of RA. JAKi have been associated with an elevated risk of herpes zoster (HZ) in patients (pts) with RA. The adjuvanted recombinant zoster vaccine (RZV, Shingrix) was shown to be well-tolerated and effective in preventing HZ in adults aged ≥ 50 years.[1] The efficacy and safety of RZV have not been studied in pts with RA while on UPA in combination with MTX.ObjectivesTo assess the immunogenicity of RZV in pts with RA receiving UPA 15 mg once daily (QD) with background MTX.MethodsEligible adults aged ≥ 50 years with RA enrolled in the ongoing SELECT-COMPARE phase 3 trial (NCT02629159) received two RZV doses, administered at the baseline and week (wk) 12 visits. Pts should have been on stable doses of UPA 15 mg QD and background MTX for ≥ 8 wks before the first vaccination and ≥ 4 wks after the second vaccination. Antibody titers were collected pre-vaccination (baseline), 4 wks post-dose 1 vaccination (wk 4), and 4 wks post-dose 2 vaccination (wk 16). The primary endpoint was the proportion of pts with a humoral response to RZV defined as ≥ 4-fold increase in pre-vaccination concentration of anti-glycoprotein E [gE] titer levels at wk 16. Secondary endpoints included humoral response to RZV at wk 4 and the geometric mean fold rise (GMFR) in anti-gE antibody levels at wks 4 and 16. Cell-mediated immunogenicity to RZV was an exploratory endpoint evaluated by the frequencies of gE-specific CD4+ [2+] T cells (CD4+ T cells expressing ≥ 2 of 4 activation markers: IFN-γ, IL-2, TNF-α, and CD40 ligand) measured by flow cytometry at wks 4 and 16 in a sub-cohort of pts.ResultsOf the 95 pts who received ≥ 1 RZV dose, 93 (98%) received both RZV doses. Pts had a mean (standard deviation) age of 62.4 (7.5) years. The median (range) disease duration was 11.7 (4.9–41.6) years and duration of UPA exposure was 3.9 (2.9–5.8) years. At baseline, all but 2 pts were receiving concomitant MTX and half (50%) were taking an oral corticosteroid (CS) at a median daily dose of 5.0 mg. One pt discontinued UPA by wk 16. Blood samples were available from 90/93 pts. Satisfactory humoral responses to RZV occurred in 64% (95% confidence interval [CI]: 55–74) of pts at wk 4 and 88% (81–95) at wk 16 (Figure 1). Age (50–< 65 years: 85% [95% CI: 75–94];≥ 65 years: 94% [85–100]) and concomitant CS (yes: 87% [77–97];no: 89% [80–98]) use at baseline did not affect humoral responses at wk 16. GMFR in anti-gE antibody levels compared with baseline values were observed at wks 4 (10.2 [95% CI: 7.3–14.3]) and 16 (22.6 [15.9–32.2]). Among the sub-cohort of pts, nearly two-thirds achieved a cell-mediated immune response to RZV (wk 4: n = 21/34, 62% [95% CI: 45–78];wk 16: n = 25/38;66% [51–81]). Within 30 days post-vaccination of either RZV dose, no serious adverse events (AEs) (Table 1) or HZ were reported. AEs that were possibly related to RZV were reported in 17% of pts. One death occurred more than 30 days after wk 16 due to COVID-19 pneumonia.ConclusionMore than three-quarters (88%) of pts with RA receiving UPA 15 mg QD on background MTX achieved a satisfactory humoral response to RZV at wk 16. In a subgroup of pts, two-thirds (66%) achieved a cell-mediated immune response to RZV at wk 16. Age and concomitant CS use did not negatively affect RZV response.Reference[1]Syed YY. Drugs Aging. 2018;35:1031–40.Table 1. Safety Results Through 30-Days Post-RZV Vaccination in UPA-Treated PatientsEvent, n (%)UPA 15 mg QD (N = 95)Any AE38 (40%)AE with reasonable possibility of being related to UPAa13 (14%)AE with reasonable possibility of being related to RZVa16 (17%)Severe AEb1 (1%)Serious AE0AE leading to discontinuation of UPA0Death0AE, adverse event;QD, once daily;RZV, adjuvanted recombinant zoster vaccine;UPA, upadacitinib.aAs assessed by the investigator.bHypersensitivity.AcknowledgementsAbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, review, and approval of the . All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Julia Zolotarjova, MSc, MWC, of AbbVie.Disclosure of InterestsKevin Winthrop Consultant of: AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Gilead, GSK, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB, Grant/research support from: AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Gilead, GSK, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB, Justin Klaff Shareholder of: AbbVie, Employee of: AbbVie, Yanxi Liu Shareholder of: AbbVie, Employee of: AbbVie, CONRADO GARCIA GARCIA: None declared, Eduardo Mysler Speakers bureau: AbbVie, Amgen, AstraZeneca, BMS, Eli Lilly, GlaxoSmithKline, Pfizer, Roche, and Sandoz, Consultant of: AbbVie, Amgen, AstraZeneca, BMS, Eli Lilly, GlaxoSmithKline, Pfizer, Roche, and Sandoz, Alvin F. Wells Consultant of: AbbVie, Amgen, BMS, Eli Lilly, Novartis, Pfizer, and Sanofi, Xianwei Bu Shareholder of: AbbVie, Employee of: AbbVie, Nasser Khan Shareholder of: AbbVie, Employee of: AbbVie, Michael Chen Shareholder of: AbbVie, Employee of: AbbVie, Heidi Camp Shareholder of: AbbVie, Employee of: AbbVie, Anthony Cunningham Consultant of: GSK, Merck Sharp & Dohme, and BioCSL/Sequirus.
ABSTRACT
BackgroundKidney transplant patients due to both primary kidney involvement of chronic/autoimmune inflammatory diseases and end-stage kidney disease related to amyloidosis are followed up in rheumatology clinics. Biological agents one of the treatment options in kidney transplant recipients with chronic/autoimmune inflammatory disease.ObjectivesHowever, there is insufficient data on the development of infection in kidney transplant recipients who received biological treatment. Herein, we aimed to determine the incidence of serious infections in patients with kidney transplant recipients who are received biological therapy.MethodsKidney transplant recipients who are received biological agents due to rheumatologic disease were included in the study. Patients' demographic features, transplantation data, biological treatment, development of infection and severity of infection were screened retrospectively. Infections that requiring hospitalization were defined as severe infections.ResultsA total of 31 patients were included in the study, 14 (45%) of whom were female and mean age was 41 ±9 years. Twenty-five patients (80%) of them were non-preemptive kidney transplant and mean duration of hemodialysis before the transplantation was 40 ±40 months. Twenty-three patients (74%) had end stage kidney failure due to FMF-amyloidosis(Figure-1-). Seventeen patients (54%) received anakinra, 11 patients (35%) received canakinumab and 3 patients (10%) received etanercept with other immunosuppressive treatment. Mean treatment duration of biological agents was 4.2±2.6 years. Two patients developed solid organ malignancy and one patient developed hematological malignancy after transplantation. Sixteen of the patients (52%) were hospitalized at least once due to infection and 4 patients (13%) died due to infection. The cause of decease in two patients was COVID-19.ConclusionRheumatic diseases are an important cause of end-stage renal disease and definitive treatment is kidney transplantation. Kidney transplant recipients due to rheumatological disease also use biological agents in the post-transplantation period. Kidney transplant recipients have higher risk for the development of infection since they receive immunosuppressive therapy and use of biologic agents may further increase the risk for development infection. Meyer et al reported that infection developed in 54 of 187 solid organ transplant recipients using biological agents.[1] Mean treatment duration of biological agents was 12 months in this study. The incidence of infection was 54% in our study. Mean treatment duration of biological agent was 4.2 year was considered main reason for higher incidence of infection in our study.Reference[1]Meyer F, Weil-Verhoeven D, Prati C, Wendling D, Verhoeven F. Safety of biologic treatments in solid organ transplant recipients: A systematic review. Semin Arthritis Rheum. 2021 Dec;51(6):1263-1273. doi: 10.1016/j.semarthrit.2021.08.013. Epub 2021 Aug 26. Erratum in: Semin Arthritis Rheum. 2022 Aug;55:152015. PMID: 34507811.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disease, which presents an immune disorder that leads to the production of autoantibodies with potential involvement of multiple organs. Infections are one of the most frequent causes of hospitalization and death in lupus patients, and SARS-CoV-2 infection has been a global threat since March 2020. Immunization of these patients has been strongly recommended, although vaccine evaluation studies have not included this profile of patients.ObjectivesTo evaluate the immunogenicity and safety after 2 doses of the vaccine against SARS-CoV2 in patients with SLE.MethodsSubgroup of SLE patients from the prospective multicenter cohort of patients with immune-mediated diseases "SAFER” – Safety and Efficacy on COVID-19 Vaccine in Rheumatic Disease, a phase IV study. Vaccination against SARS-CoV-2 took place with vaccines approved by Brazilian regulatory bodies CoronaVac (Inactivated SARS-CoV-2 Vaccine), ChadOx-1 (AstraZeneca) and BNT162b2 (Pfizer-BioNTech) and this project followed in line with the guidelines of the National Immunization Plan in Brazil. Patients aged 18 years or older with a previous diagnosis of SLE (according to the 2019 ACR/EULAR criteria) were included. Patients were evaluated by telephone contact and in a face-to-face visit on the 28th day after each dose. Patients were followed up by means of blood collection for measurement of IgG antibody against SARS-COV-2 by chemiluminescence and disease activity assessed using SLEDAI-2K score.ResultsA total of 367 individuals with SLE were included, of whom 207 received 2 doses of CoronaVac, 128 received 2 doses of ChadOx-1 and 32 received 2 doses of BNT162b2. 90% of the subjects were female with a mean age of 37 years. About 42% (154) of the individuals included did not have any other associated comorbidity. 50% (182) of patients were using oral glucocorticoids and azathioprine was the most frequent immunosuppressive therapy. Regarding disease activity parameters, 38% (140) of patients had zero SLEDAI-2K at baseline and 41% (147) had zero SLEDAI-2K 28 days after the 2nd dose. Anti-DNA positivity was 30.7% (16/52) at inclusion and 32.6% (17/52) 28 days after the 2nd dose. Complement consumption was present in 18% (10/55) at inclusion and in 14.5% (8/55) 28 days after the 2nd vaccine dose. The geometric mean titers of IgG antibodies against SARS-COV-2 increased in the different vaccine groups, log 2.27 BAU/mL at inclusion and log 5.58 BAU/mL 28 days after the 2nd dose. Antibody titers after second dose varied between different vaccines, 4.96 BAU/mL CoronaVac, 6.00 BAU/mL ChadOx-1 and 7.31 BAU/mL BNT162b2 vaccine, p < 0.001. Only 3.54% (13/367) patients had covid-19 infection after the 15th day of the second dose of immunization, 9 of them having received 2 doses of CoronaVac, 4 of them of ChadOx-1 and none of them receiving BNT162b2, with p-value of 0.63.ConclusionThis study suggests that vaccines against SARS-COV-2 are safe in SLE patients. Induction of immunogenicity occurred in different vaccine regimens. Only 3.5% of individuals had COVID-19 infection with no difference between the types of vaccines evaluated. Future analyzes to explore the association of the effect of immunosuppressive medication, as well as the impact of booster doses and longer follow-up on clinical outcome will be performed.References[1]Mason A, et al. Lupus, vaccinations and COVID-19: What we know now. Lupus. 2021;30(10):1541-1552.[2]Furer V, Eviatar T, Zisman D, et al. Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in adult patients with autoimmune inflammatory rheumatic diseases and in the general population: A multicentre study. Ann Rheum Dis. 2021;80(10):1330-1338.[3]Izmirly PM, Kim MY, Samanovic M, et al. Evaluation of Immune Response and Disease Status in SLE Patients Following SARS-CoV-2 Vaccination. Arthritis Rheumatol. Published online 2021.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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BackgroundInfections constitute an important and frequent cause of morbidity and mortality in patients with chronic inflammatory and systemic autoimmune rheumatic diseases. In rheumatoid arthritis (RA), this increased risk has been related to the immune system alterations inherent to the disease, the drugs used to control it (corticosteroids, DMARDs and immunosuppressants) and associated comorbidities. Most studies focus on the search for factors associated with the development of infections but do not explore the worst outcome: patient failure.ObjectivesTo identify factors that help to predict an unfavorable outcome (exitus) after a severe infection in patients with rheumatoid arthritis.MethodsThis study was a retrospective case-control study at a single institution over a 10-year period. Patients with a diagnosis of rheumatoid arthritis with hospital admission for infection from January 1, 2010, to December 31, 2019 (pre-pandemic SARS-COV-2) were selected. The main variable was exitus due to the infectious episode. We collected: age, sex, time of evolution of RA, previous treatment and at the time of admission, number of admissions for infection, location of the infection, comorbidities, and other associated serious diseases. The statistics included a descriptive analysis of the different variables (expressed as median and interquartile range -IR- for quantitative variables and percentages for qualitative variables), and the association study using the χ2 test or Fisher's exact test for qualitative variables, and t-student or Mann-Whitney U and Kruskal Wallis for quantitative variables.ResultsWe obtained 152 patients (71.7% female, 28.3% male), with a total of 214 episodes of admission for infection (115 patients with 1 episode (75.7%), 25 (16.4%) with 2 episodes, 6 being the maximum number of episodes recorded). The median age at admission was 77 years, and the median time of RA evolution was 8 years (IR 4-16). The location of the infection responsible for admission was mainly respiratory and urinary. Forty-eight patients died in the episode (31.6% of the sample, 15 males and 33 females, median age 81.5 years (IR 69.5-86.5)). Comparing the patients with unfavorable outcomes (exitus) with the rest, we only found a statistically significant difference in the number of previous admissions (p=0.011), and in the coexistence of some other serious disease (exitus 85.4%, rest 61.5% p=0.003). There were no differences by sex, age, time of RA evolution, drugs, location of the infection, or comorbidities.ConclusionA history of hospital admission due to infection, and having another serious disease, are factors associated with an unfavorable outcome (exitus) in patients with RA admitted for an infectious process.References[1] Listing J, Gerhold K, Zink A. The risk of infections associated with rheumatoid arthritis, with its comorbidity and treatment. Rheumatology 2013;52(1):53-61.[2] George MD, Baker JF, Winthrop K, Hsu JY, Wu Q, Chen L, et al. Risk for serious infection with low-dose glucocorticoids in patients with Rheumatoid Arthritis: A cohort study. Ann Intern Med. 2020;173(11):870-8.[3] Singh JA, Cameron C, Noorbaloochi S, Cullis T, Tucker M, Christensen R, et al. Risk of serious infection in biological treatment of patients with rheumatoid arthritis: A systematic review and meta-analysis. The Lancet. 2015;386(9990):258-65.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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BackgroundSafety and efficacy of updated bivalent vaccines, containing both the original vaccine variant of SARS-CoV-2 Spike and either Omicron variants BA.1 or BA.4/5, are of particular interest in arthritis patients on immunosuppressive therapies. With the continuous emergence of new viral variants, it is important to evaluate whether updated vaccines induce more adverse events in this patient group.ObjectivesTo examine if a second booster dose with updated bivalent vaccine increases the risk of adverse events, compared to the first booster dose with monovalent vaccines.MethodsThe prospective Nor-vaC study investigates vaccine responses in patients with immune mediated inflammatory diseases using immunosuppressive therapies (1). The present analyses included arthritis patients who received two booster doses. Patients received available vaccines according to the Norwegian vaccination program. The current recommendation in the Norwegian arthritis population is a three-dose primary vaccination series followed by two booster doses. Adverse events following vaccines doses were self-reported through questionnaires. Adverse events following the first (monovalent) and second (bivalent) booster were compared with McNemar's test.ResultsBetween 7th of July 2021 and 6th of December 2022 a total of 243 arthritis patients (127 rheumatoid arthritis, 65 psoriatic arthritis, 51 spondyloarthritis) on immunosuppressive therapies (Table 1) received a first, monovalent (BNT162b2, mRNA-1273) and a second, bivalent booster dose (BNT162b2 (WT/OMI BA.1), mRNA-1273.214, BNT162b2 (WT/OMI BA.4/BA.5)). Adverse events were recorded within 2 weeks in all patients (Figure 1). In total, 45 vs 49 (19% vs 20 %) patients reported any adverse event after a second, bivalent booster dose, compared to the first, monovalent booster, respectively. There was no significant difference in adverse events overall (p= 0.57). The most common adverse events after the second booster were pain at injection site (12 %), flu-like symptoms (9 %) and headache (6 %). No new safety signals emerged. A total of 15 (6 %) patients reported a disease flare after receiving the second, bivalent booster, compared to 21 (8 %) after the first, monovalent booster.ConclusionThere was no difference in adverse events between the monovalent, first booster, and the bivalent, second booster, indicating that bivalent vaccines are safe in this patient group.Reference[1]Syversen S.W. et al Arthritis Rheumatol 2022Table 1.Demographic characteristics and immunosuppressive medication in patients receiving a 1st monovalent and a 2nd bivalent booster dose.CharacteristicsPatients, n (%)Total243Age (years), median (IQR)61 (52-67)Female152 (63)Immunosuppressive medicationTNFi monoa75 (31)TNFi comboa+b72 (30)Methotrexate62 (26)Rituximab9 (4)IL-inhibitorsc6 (2)JAK-inhibitorsd11 (5)Othere8 (3)1st boosterBNT162b2106 (44)mRNA-1273137 (56)2nd boosterBNT162b2 (WT/OMI BA.1)65 (25)BNT162b2 (WT/OMI BA.4/BA.5)120 (47)mRNA-1273.214 (WT/OMI BA.1)58 (23)Results in n (%) unless otherwise specified.aTumor necrosis factor inhibitors: infliximab, etanercept, adalimumab, golimumab, certolizumab pegol.bCombination therapy: methotrexate, sulfasalazine, leflunomide, azathioprine.cInterleukin inhibitors: tocilizumab, secukinumab.dJanus kinase inhibitors: filgotinib, baricitinib, upadacitinib, tofacitinib.eOther: abatacept, sulfasalazine, leflunomide, azathioprine.Figure 1.Adverse events after bivalent vaccine as a 2nd booster dose compared to a monovalent vaccine as a 1st booster dose.[Figure omitted. See PDF]AcknowledgementsWe thank the patients and health-care workers who have participated in the Norwegian study of vaccine response to COVID-19. We thank the patient representatives in the study group, Kristin Isabella Kirkengen Espe and Roger Thoresen. We thank all study personnel, laboratory personnel, and other staff involved at the clinical departments involved, particularly Synnøve Aure, Margareth Sveinsson, May Britt Solem, Elisabeth Røssum-Haaland, and Kjetil Bergsmark.Disclosure of InterestsHilde Ørbo: None declared, Ingrid Jyssum: None declared, Anne Therese Tveter: None declared, Ingrid E. Christensen: None declared, Joseph Sexton: None declared, Kristin Hammersbøen Bjørlykke Speakers bureau: Janssen-Cilag, Grete B. Kro: None declared, Tore K. Kvien Speakers bureau: Amgen, Celltrion, Egis, Evapharma, Ewopharma, Hikma, Oktal, Sandoz, Sanofi, Consultant of: AbbVie, Biogen, Celltrion, Eli Lilly, Gilead, Mylan, Novartis, Pfizer, Sandoz, Sanofi, Grant/research support from: AbbVie, Amgen, BMS MSD, Novartis, Pfizer, UCB, Ludvig A. Munthe Speakers bureau: Novartis, Cellgene, Gunnveig Grodeland Speakers bureau: Bayer, Sanofi, ThermoFisher, Consultant of: AstraZeneca, Siri Mjaaland: None declared, John Torgils Vaage: None declared, Espen A Haavardsholm Speakers bureau: Pfizer, UCB, Consultant of: AbbVie, Boehringer-Ingelheim, Eli Lilly, Gilead, Kristin Kaasen Jørgensen Speakers bureau: Bristol-Myers Squibb, Roche, Sella Aarrestad Provan: None declared, Silje Watterdal Syversen: None declared, Guro Løvik Goll Speakers bureau: AbbVie/Abbott, Galapagos, Pfizer, UCB, Consultant of: AbbVie/Abbott, Galapagos, Pfizer, UCB.
ABSTRACT
BackgroundA 3rd COVID-19 vaccination is currently recommended for patients under immunosuppression. However, a fast decline of antibodies against the SARS-CoV-2 receptor-binding domain (RBD) of the spike protein has been observed.ObjectivesIt remains unclear whether immunosuppressive therapy affects kinetics of humoral and cellular immune responses.Methods50 patients under immunosuppression and 42 healthy controls (HCs) received a 3rd dose of an mRNA-based vaccine and were monitored over a 12-weeks period. Humoral immune response was assessed 4 and 12 weeks after 3rd dose. Antibodies were quantified using the Elecsys Anti-SARS-CoV-2 Spike immunoassay against the receptor-binding domain (RBD) of the spike protein. SARS-CoV-2-specific T cell responses were quantified by IFN-γ ELISpot assays. Adverse events, including SARS-CoV-2 infections, were monitored over a 12-week period.ResultsAt week 12, reduced anti-RBD antibody levels were observed in IMID patients as compared to HCs (median antibody level 5345 BAU/ml [1781 – 10208] versus 9650 BAU/ml [6633 - 16050], p < 0.001). Reduction in relative antibody levels was significantly higher in IMID patients as compared to HCs at week 12 (p < 0.001). Lowest anti-RBD antibody levels were detected in IMID patients who received biological diseases modifying anti-rheumatic drugs (DMARDs) or a combination therapy with conventional synthetic and biological DMARDs. Number of SARS-CoV-2-specific T cells against wildtype and Omicron variants remained stable over 12 weeks in IMID patients. No serious adverse events were reported.ConclusionDue to a fast decline in anti-RBD antibodies in IMID patients an early 4th vaccination should be considered in this vulnerable group of patients.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsDaniel Mrak Consultant of: AstraZeneca, Felix Kartnig: None declared, Daniela Sieghart: None declared, Elisabeth Simader Speakers bureau: Lilly, Helga Radner Speakers bureau: Gilead, Merck Sharp and Pfizer, Peter Mandl: None declared, Lisa Göschl: None declared, Philipp Hofer: None declared, Thomas Deimel: None declared, Irina Gessl: None declared, Renate Kain Speakers bureau: Otsuka, Consultant of: AstraZeneca, Takeda Pharma, MEDahead and Janssen Cilag, Stefan Winkler: None declared, Josef S. Smolen Consultant of: AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celltrion, Gilead-Galapagos, Janssen, Lilly, Pfizer, R-Pharma, Samsung, Sanofi, Chugai, Merck Sharp & Dohme, Novartis-Sandoz Roche, Samsung and UCB, Grant/research support from: Abbvie, AstraZeneca, Lilly, Novartis, and Roche, Thomas Perkmann: None declared, Helmuth Haslacher Grant/research support from: Glock Health, BlueSky Immunotherapies and Neutrolis, Daniel Aletaha Speakers bureau: Abbvie, Amgen, Galapagos, Lilly, Janssen, Merck, Novartis, Pfizer, Sandoz, and Sanofi, Consultant of: Abbvie, Amgen, Galapagos, Lilly, Janssen, Merck, Novartis, Pfizer, Sandoz, and Sanofi, Grant/research support from: Abbvie, Amgen, Galapagos, Lilly, Janssen, Merck, Novartis, Pfizer, Sandoz, and Sanofi, Leonhard Heinz: None declared, Michael Bonelli Consultant of: EliLilly.
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BackgroundPatients with pre-existing rheumatic diseases may be exacerbated during SARS-CoV-2 infection, or may develop new autoimmune features. Furthermore, immunosuppressive agents used to treat autoimmunity-inflammation as well as comorbidities can also affect the disease outcome.ObjectivesTo evaluate the outcome of rheumatic diseases after Covid 19 infection in patients diagnosed with rheumatic diseases, under various immunosuppressive treatment, as well as the effects of vaccines against Covid or antiviral treatment in this sensitive population group.MethodsDuring the pandemic, 1493 patients with autoimmune or autoinflammatory disease who were continuously followed up in two tertiaries hospitals in northern and northwestern Greece were included in the current study. The patients were compared with 769 controls after adjustment for age, sex, weight, vaccination status and comorbidities. Of the 1493 patients, 648 had rheumatoid arthritis, 282 psoriatic arthritis, 173 ankylosing spondylitis, 122 systemic lupus erythematosus, 98 Sjogren's syndrome, 43 polymyalgia rheumatica, 34 mixed connective tissue disease or overlapping syndromes, 31 vasculitis, 27 systemic sclerosis, 18 myositis, 10 Behcet syndrome, 5 primary antiphospholipid syndrome and 2 had Familial Mediterranean Fever. The vast majority of patients and controls were fully vaccinated (82%) and 397 patients received antiviral treatment, 94% of them were fully vaccinated.ResultsCovid 19 disease in vaccinated patients with rheumatic diseases was shown to perform the same or about the same as those in the control group after adjustment for risk factors for severe disease. 19 of our patients required admission in the intensive care unit (62% full vaccinated) while a total of 12 died (66% non vaccinated). Major risk factors for severe disease were previous respiratory failure, chronic renal impairment, obesity, and failure to receive antiviral therapy. It was also shown that infection with Covid led to an exacerbation or induction of autoimmune disorders in 25 of the participants.ConclusionIn this large cohort, Covid 19 disease was shown to affect patients with autoimmune rheumatic diseases the same or approximately the same way as the general population if they are fully vaccinated and if they start timely antiviral treatment where indicated. Further research and monitoring of the results after the multiple mutations of the virus is advisable.ReferencesNone.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
ABSTRACT
BackgroundThe Covid-19 pandemic has put patients with rheumatic diseases in front of a number of obstacles that had to be solved together with Bulgarian rheumatologists. The lockdowns and restrictive measures have made it difficult for people with rheumatic diseases to have access to timely hospital and pre-hospital care. A number of digital solutions have been implemented to address these issues.ObjectivesTo highlight the problems that patients with rheumatic diseases had during the Covid-19 pandemic;access to rheumatologists and the effectiveness of hospital and pre-hospital care during the pandemic, access to treatment, changes of treatment;communication between physicians and patients, the impact of the pandemic on work, social contacts, hobbies.MethodsAn anonymous survey was conducted online and by telephone. The survey was developed by Medical university, Plovdiv, University hospital "Kaspela”:, Plovdiv, Bulgarian Association for Musculoskeletal Ultrasound, Bulgarian organization for people with rheumatic diseases;Association for patients with autoimmune diseases.Number of participants: 1205 patients with RMD's.Age range: 18-82ResultsFace to face meetings with doctors have been limited during the pandemic.Visits to the rheumatologist's office are significantly reduced and phone, email, text messaging, online consultations were preferred as communication channels.Before the pandemic, 76% of respondents most often communicated with their physicians by visiting their practice, during the pandemic their relative share decreased to 46%, with a significant difference of 30%Phone consultations: patients using this type of communication increasing from 38% before the pandemic to 56% during the pandemic, a significant difference of 18%The percentage of patients who communicated via text or email rises from 10% to 17 %.It has become apparent that Digital transformation is needed and patients and physicians should work together to achieve it and to be established in Bulgaria.245 patients reported a change in their treatment. Of these: (30%) reduced the dose of their medications, 119 (49%) increased the dose and the remaining 55 (21%) stopped their therapy.From the responses of the respondents, it is clear that 71% have not experienced a change in their work during the COVID-19 pandemic, 17% have worked from home.From the responses of the respondents, it is clear that 71% have not experienced a change in their work during the COVID-19 pandemic, 17% have worked from home, 4% have been fired, 3% have left their jobs due to the risk of their health and 5% left their jobs for other reasons.ConclusionThe Covid-19 pandemic has shown that the digital transformation in rheumatology care can be an efficient alternative to some of the services offered to patients with rheumatic diseases in Bulgaria (especially secondary examinations and therapy monitoring examinations). The results of the conducted survey could be used to support digitization in healthcare in Bulgaria.Very important was the collaboration between the patient organizations and the Bulgarian Association for Musculoskeletal Ultrasound, Medical University, Plovdiv and the rheumatologists from University hospital "Kaspela” Plovdiv.References[1]Gianfrancesco M, Hyrich KL, Al-Adely S, et al. Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry. Ann Rheum Dis 2020;79: 859–66.[2]Monti S, Balduzzi S, Delvino P, Bellis E, Quadrelli VS, Montecucco C. Clinical course of COVID-19 in a series of patients with chronic arthritis treated with immunosuppressive targeted therapies. Ann Rheum Dis 2020;79: 667–68.[3]Dejaco, C.;Alunno, A.;Bijlsma, J.W.;Boonen, A.;Combe, B.;Finckh, A.;Machado, P.M.;Padjen, I.;Sivera, F.;Stamm, T.A.;et al. Influence of COVID-19 pandemic on decisions for the management of people with inflammatory rheumatic and musculoskeletal diseases: A survey among EULAR countries. Ann. Rheum. Dis. 2020AcknowledgementsBul arian organization for people with rheumatic diseases.Association for patients with autoimmune diseases.Bulgarian Association for Musculoskeletal Ultrasound.Disclosure of InterestsNone Declared.
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BackgroundAmid the coronavirus disease 2019 (COVID-19) crisis, two messenger RNA (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have benefited most people worldwide. While healthy people can acquire sufficient humoral immunity against COVID-19 even in the elderly by vaccination with three doses of vaccine., recent studies have shown that complex factors other than age, including the type of vaccines and immunosuppressive drugs, are associated with immunogenicity in patients with rheumatic musculoskeletal disease (RMD). Identifying factors that contribute to the vulnerability of those patients to acquire not only humoral but also cellular immunity to SARS-CoV-2 despite multiple vaccinations is crucial for establishing an appropriate booster vaccine strategy.ObjectivesTo assess humoral,and T cell immune responses after third doses of mRNA vaccines against SARS-CoV-2.MethodsThis prospective observational study included consecutive RMD patients treated with immunosuppressant who received three doses of mRNA vaccines including BNT162b2 and mRNA-1273. Blood samples were obtained 2-6 weeks after second and third dose of mRNA vaccines. We measured neutralizing antibody titres, which against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 and seroconversion rates to evaluate the humoral responses. We also assessed T-cell immunity responses using interferon releasing assay against SARS-CoV-2.ResultsA total of 586 patients with RMD treated with mmunosuppressive treatments were enrolled. The mean age was 54 years, and 70% of the patients were female. Seroconversion rates and neutralizing antibody titres after third vaccination of SARS-CoV-2 were significantly higher compared to those after second vaccination (seroconversion rate, 94.5% vs 83.6%, p<0.001;titres of neutralizing antibody, 48.2 IU/mL vs 11.0 IU/mL, p<0.001, respectively). Interferon releasing assay after third vaccinations demonstrated that T cell reaction against SARS-CoV-2 was also increased from that of second vaccination (interferon for antigen 1, 1.11.9 vs 0.61.9, p=0.004,interferon for antigen 2, 1.72.6 vs 0.82.3, p=0.004). Humoral and cellular immunogenicity did not differ between the types of third vaccination including full dose of BNT162 and half dose of mRNA1273.(neutralizing antibody titers, 47.8±76.1 IU/mL vs 49.0±60.1 IU/mL, p<0.001;interferon for antigen 1, 1.12.0 vs 1.01.5, p=0.004, respectively). Attenuated humoral response to third vaccination was associated with BNT162b2 as second vaccination age (>60 years old), glucocorticoid (equivalent to prednisolone > 7.5 mg/day), and immunosuppressant use including mycophenolate, and rituximab. On another front, use of mycophenolate and abatacept or tacrolimus but not rituximab were identified as negative factors for T-cell reactions against SARS-CoV-2. Although 53 patients (9.0%) who had been immunised with third-vaccination contracted COVID-19 during Omicron pandemic phase, no one developed severe pulmonary disease that required corticosteroid therapy.ConclusionOur results demonstrated third mRNA vaccination booster of SARS-CoV-2 contributed to restore both humeral and cellular immunity in RMD patients with immunosuppressants. We also identified that certain immunosuppressive therapy with older RMD patients having BNT162b2 as a second vaccination may need additional booster vaccination.Reference[1]Furer V, Eviatar T, Freund T, et al. Ann Rheum Dis. 2022 Nov;81(11):1594-1602. doi: 10.1136/ard-2022-222550.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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BackgroundCOVID-19 has shaped the world over the last 3 years. Although the risk for severe COVID-19 progression in children is low it might be aggravated by chronic rheumatic disease or treatment with immunosuppressive drugs.ObjectivesWe analyzed clinical data of COVID-19 cases among paediatric patients with rheumatic diseases reported to BIKER between March 2020 and December 2022.MethodsThe main task of the German BIKER (Biologics in Pediatric Rheumatology) registry is safety monitoring of biologic therapies in JIA. After the onset of the COVID-19 pandemic, the survey was expanded with a standardized form to proactively interview all participating centers about occurrence, presentation and outcome of SARS-CoV-2 infections in children with rheumatic diseases.ResultsA total of 68 centres participated in the survey. Clinical data from 928 COVID infections in 885 patients with rheumatic diseases could be analyzed. JIA was the most common diagnosis with (717 infections), followed by genetic autoinflammation (103 infections), systemic autoimmune diseases (78 infections), idiopathic uveitis (n=25), vasculitis (n=5).In 374 reported COVID infections (40%), patients were receiving conventional DMARDs, in 331 (36%) biologics, mainly TNF inhibitors (TNFi, n=241 (26%)). In 567 reports (61%) patients used either a biologic or a DMARD, in 339 reports patients (37%) did not use any antirheumatic medication including steroid.Over the last 3 years, COVID-19 occurred in Germany in 5 distinguishable waves, calendar weeks (CW) 10-30 in 2020, CW 21/2020 – 8/2021(both predominantly wild-type variant), CW 9-27 in 2021 (Alpha variant in the majority of infections), CW 28-51 in 2021 (Delta variant), since CW 52/2021 (several Omikron variants;Robert-Koch Institute: VOC_VOI_Tabelle.xlsx;live.com))In our cohort, patients with SARS-CoV-2 infection were slightly older during the 1st and 2nd wave (mean age 12.7+/-3.5 and 12.8+/-4.3 years) compared to the 4th and 5th wave with 11.4+/-3.9 and 11.4+/-4.2 years;p=0.01.160 asymptomatic SARS-CoV-2 infections were reported, frequencies of symptoms associated with COVID-19 are shown in table 1.Five patients were hospitalized for 4-7 days. A 3½-year-old female patient succumbed during the first wave with encephalopathy and respiratory failure. The patient had been treated with MTX and steroids for systemic JIA. Genetic testing revealed a congenital immunodeficiency. No other patient needed ventilation or intensive care. One case of uncomplicated PIMS in an MTX treated JIA patient was reported.The duration of SARS-CoV-2 infection-associated symptoms was markably shorter during the 5th wave with 6.7+/-5.1 days, compared with reports from the other 4 waves (Table1).The duration of symptoms was higher in MTX treated patients (10.2+/-8.4 days) compared to patients without treatment (7.7+/-10.8;p=0.004) or patients treated with TNFi (8.2+/-4.8, p=0.002). Although patients treated with steroids also had a longer duration of symptoms (9.7+/-7.0), this was not significant.ConclusionExcept for one patient with congenital immunodeficiency who died, no case of severe COVID-19 was reported in our cohort. At the time of infection, over 60% of patients had been treated with conventional DMARDs and/or biologics. Although MTX treated patients had a slightly longer duration of symptoms, antirheumatic treatment did not appear to have a negative impact on severity or outcome of SARS-CoV-2 infection.Table 1.Characteristics and frequency of symptoms in SARS-CoV-2 infectionsN or mean (SD)1st wave N=202nd wave N=843rd wave N=384th wave N=1245th wave N=662female14532775432age at COVID-19, years12.7 (3.5)12.8 (4.3)11.8 (3.5)11.4 (3.9)11.4 (4.2)asymptomatic126132694duration of symptoms;days,11.9 (14.7)9.2 (7.0)14.1 (11.6)10.3 (7.6)6.7 (5.1)fever1218541306cough1015652245rhinitis5261344289headache4161227171sore throat61139132musculosceletal pain2751348loss of smell/taste71162113fatigue4882680dizziness122116gastrointestinal symptoms151864dyspnea1117pneumonia11bronchitis1REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Inter stsAriane Klein Speakers bureau: Novartis, Toni Hospach Speakers bureau: Speaking fee Novartis and SOBI., Frank Dressler Speakers bureau: Abbvie, Novartis, Pfizer, Advisory Boards Novartis and Mylan, Daniel Windschall Grant/research support from: research funds by Novartis, Roche, Pfizer, Abbvie, Markus Hufnagel: None declared, Wolfgang Emminger: None declared, Sonja Mrusek: None declared, Peggy Ruehmer: None declared, Alexander Kühn: None declared, Philipp Bismarck: None declared, Maria Haller: None declared, Gerd Horneff Speakers bureau: Pfizer, Roche, MSD, Sobi, GSK, Sanofi, AbbVie, Chugai, Bayer, Novartis, Grant/research support from: Pfizer, Roche, MSD, AbbVie, Chugai, Novartis.
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BackgroundUnderstanding the dynamics of humoral immunity after COVID-19 vaccination is crucial in developing vaccination strategies. Antibody response patterns are more complex in patients with rheumatoid arthritis (RA) because of their underlying autoimmunity and immunosuppressive medications. The kinetics of vaccine response in RA patients are not well understood.ObjectivesTo construct a model of antibody response to COVID-19 vaccination in patients with RA.MethodsTwo patient groups were included for the study. The first group was composed of RA patients who were enrolled for influenza vaccination study between Oct 6, 2021 and November 3, 2021, in whom serial serum samples were obtained 0, 4, 16 weeks after vaccination. The second group was consecutively enrolled from outpatient clinic between October 6, 2021 and June 3, 2022, in whom serum sample was obtained once. After collecting data on demographics, vaccination and infection history of COVID-19 were obtained by self-report via questionnaire and data from Korean center for disease control. We then measured antibody titers against receptor binding domain of spike protein (anti-RBD) and nucleocapsid (anti-N), using Chemiluminescence microparticle immunosaasy (Abbott, USA) and Electrochemiluminescence immunoassay (Roche, Germany) respectively. The anti-RBD titer was log-transformed to improve normality. Time from vaccination and log of anti-RBD titer was modeled using fractional polynomial. Covariates including age, sex, BMI, underlying disease and immunosuppressive drugs were analyzed using Generalized Estimating Equations to account for repeated measured from a subject.ResultsA total of 736 patients (1042 samples) were enrolled. After excluding patients who experienced COVID-19 infection before sampling (n=84), those unvaccinated (n=44) and uncertain COVID-19 infection history (n=59), the data on 778 samples from 549 patients were analyzed (Group 1: 125, Group 2: 424). Antibody titer reached peak at 12 days after vaccination and decreased exponentially (Figure 1) which fell to 36.5% from peak after 2 months. Compared to the first vaccination, the 3rd and 4th vaccination significantly shifted anti-RBD antibody response curve (28 times, 95% CI 4~195;32 times 95% CI 4~234, respectively). However, there was no significant shift after the 4th vaccination from the 3rd vaccination (p=0.6405). Multivariable analysis showed that number of vaccinations and sulfasalazine (coefficient: 0.40, 95% CI 0.12~0.68) increased vaccine response but age (coefficient: -0.03, 95% CI -0.04~-0.02), abatacept (coefficient: -2.07, 95% CI -3.30~-0.84) and, JAK inhibitor (coefficient: -0.82, 95% CI -1.34~-0.31) decreased vaccine response.ConclusionAnti-RBD response to COVID-19 vaccination showed a peak at 12 days after vaccination and then exponentially decreased in patient with RA. The antibody response is affected by age and medications used for the treatment of RA.Table 1.ln[RBD (U/ml)]coefficient (univariable)95% CIp-valuecoefficient (multivariable)95% CIp-valuesex (female)0.17-0.22, 0.550.393---age-0.02-0.03, -0.01<.001**-0.03-0.04, -0.02<.001**DM0.11-0.27, 0.500.568---HTN-0.38-0.69, -0.070.018*---CKD0.680.07, 1.290.030*---RA duration (yr)-0.04-0.06, -0.010.001**---Pd (mg/d)-0.06-0.11, 0.000.035*---MTX use-0.23-0.52, 0.050.105---HCQ use0.01-0.28, 0.290.965---SSZ use0.450.07, 0.840.022*0.400.12,0.680.005**LEF use0.00-0.37, 0.370.988---TNF inhibitors use0.29-0.16, 0.730.208---Abatacept use-2.07-3.14, -0.99<.001**-2.07-3.30, -0.840.001**JAK inhibitors use-0.88-1.52, -0.240.007**-0.82-1.34, -0.310.002**Time (months)log(t)-1.96-2.37, -1.54<.001**-1.90-2.29, -1.50<.001**t
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BackgroundThe COVID-19 pandemic caused concerns whether patients with rheumatic musculoskeletal disease (RMD) treated with conventional (cs) or biologic (b) disease modifying drugs (DMARDs) and/or prednisolone exhibit an adequate immune response to the applied SARS-CoV2 vaccines.ObjectivesWe established the DECODIR study to assess and compare the efficacy of the SARS-CoV2 vaccines administered as part of the national vaccine roll-out: BNT162b2 vaccine (Pfizer/BioNTech) and mRNA-1273 vaccine (Moderna). The vaccines were offered as two doses four weeks apart;followed by a booster vaccination six months later. This national regimen included inflammatory rheumatic patients regardless of their respective anti-inflammatory treatment. We used patients' SARS-CoV2 IgG serum level as proxy for vaccination response (1).MethodsThe study was conducted as a longitudinal prospective cohort study. Patients with rheumatoid arthritis (RA), spondyloarthropathies (SpA) or psoriatic arthritis (PsA) receiving their outpatient treatment at the Danish Hospital for Rheumatic Diseases, Sonderborg, and monitored in the Danish DANBIO registry, were included.Blood samples, Disease activity and treatment information (cs/bDMARD, prednisolone) were collected at baseline (i.e. prior to vaccination), after six weeks, six and twelve months. SARS-CoV-2 IgG levels in serum were assessed by ELISA (Thermo-Fischer), and manufacturer's cut-off (>=10 EliA U/mL) selected as definition of sufficient IgG response. Antibody response was measured and compared at all four time points.Associations between antibody response, age, gender, disease (RA/PsA/SpA), treatment (none, cs/bDMARD or prednisolone) and disease activity were tested using proportional odds regression and bootstrapped tests of medians. Results were reported using mean, median (IqR) and bootstrapped 95% confidence interval (CI) of the median.ResultsA total of 243 patients were included at baseline and all were followed-up after six weeks;data from 233 patients were available at six months and for 229 patients at twelve months' follow-up. Those 229 patients had completed the national vaccination programme.The measurements performed 6 months after baseline demonstrated a per se decrease of IgG levels for the whole study population (median of 2.08 EliA U/mL at 6 months vs. 16 EliA U/mL at 6 weeks). The final measurements performed after twelve months demonstrated a significant increase of IgG levels. Thus, the completed vaccination programme, was followed by a significant increase in IgG levels (median of 100 EliA U/mL at twelve months vs. 16.5 EliA U/mL at six months, p < 0.001).Sufficient response rates were now recorded in all treatment scenarios, also in patients treated with prednisolone or combination of csDMARD and bDMARD. These two groups were at 6 months characterized by significant lower response rates, when compared with patients without any DMARD treatment.ConclusionCompleted vaccination programme defined as two doses plus booster vaccination resulted in a sufficient vaccination response as measured by IgG levels regardless of RA treatment.It is noteworthy that IgG levels increased markedly in patients treated with a combination of cs/bDMARD or oral prednisolone, who had low IgG levels (below manufacturer's cut-off >=10 EliA U/mL) after 6 months. Our results strongly support the efficacy of the complete vaccination programme including the 3rd booster vaccine in patients with inflammatory rheumatic diseases.Figure 1.Serum IgG-levels at baseline, 6 weeks, 6 months and 12 months;stratified by antirheumatic treatment. (Box plot showing median and interquartile range).[Figure omitted. See PDF]Reference[1]Schreiber K. et al. Reduced Humoral Response of SARS-CoV-2 Antibodies following Vaccination in Patients with Inflammatory Rheumatic Diseases— an Interim Report from a Danish Prospective Cohort Study. Vaccines 2022, 10(1), 35;https://doi.org/10.3390/vaccines10010035AcknowledgementsWe acknowledge all patients contributing to the DANBIO registry.The Danish Rheumatologic Biobank is a knowledged for handling and storage of biological material.Lab chieftechnician Charlotte Drachmann is acknowledged for her assistance.Disclosure of InterestsChristine Graversgaard: None declared, Karen Schreiber Speakers bureau: Lilly, UCB, Henning Jakobsen: None declared, Randi Petersen: None declared, Anders Bo Bojesen: None declared, Niels Steen Krogh: None declared, Bente Glintborg Grant/research support from: Pfizer, AbbVie, BMS, Sandoz, Merete Lund Hetland: None declared, Oliver Hendricks Speakers bureau: Pfizer, Lilly, Novartis.
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This paper presents raw plant materials and their characteristic compounds which may affect the immune system. Plant-derived agents in specific doses affect the body's non-specific, antigen-independent defense system. They have immunostimulatory effects on the entire immune regulatory system. They can enhance the immune response through various factors such as macrophages, leukocytes, and granulocytes, as well as through mediators released by the cellular immune system. This paper was inspired by the threats caused by the COVID-19 pandemic. The proper functioning of the immune system is important in limiting the effects of viral infection and restoring the normal functioning of the body. This paper also emphasizes the importance of the skillful use of plant immunostimulants by potential patients, but also by those who prescribe drugs. It is important not only to choose the right plant drug but above all to choose the correct dose and duration of treatment.
ABSTRACT
BackgroundPatients with autoimmune rheumatic diseases (ARDs) under moderate/severe immunosuppression are considered a high-risk population to develop severe Covid-19 infection.ObjectivesThe aim of our study was to describe the clinical characteristics and the outcome of patients with ARD who contracted a Sars-Cov-2 infection.MethodsAmong patients with ARD being followed in our tertiary outpatient rheumatology clinic, we retrospectively identified those infected with SARS-CoV-2 between the beginning of the pandemic and August 2022. Patients' medical files were reviewed for demographics (age, gender and comorbidities) and disease-related characteristics, as well as coronavirus disease (COVID-19) characteristics, including vaccination status, treatment, and outcomes (covid-19 severity, hospitalization, death).ResultsA total of 209 cases of ARD patients with confirmed Covid-19 infection were recorded. Most of them were women (62.7%), with a mean age of 52.4± 13.8 years. The most prevalent ARDs were seronegative spondyloarthropathies (28.7%), systematic lupus erythematosus (21.5%), rheumatoid arthritis (16.5%), and systemic sclerosis (11.5%). More than half of the patients received corticosteroids (57.8%), while the most frequently used immunosuppressants were hydroxychloroquine (30.9%), TNF inhibitors (26.5%), mycophenolate mofetil (24.0%), methotrexate (19.1%) and rituximab (15.2%). One hundred and fifty-eight (76%) patients were either on remission or had mild disease activity. Most of the patients (131/209) had at least one comorbidity, more commonly arterial hypertension (48.5%) and pulmonary disease (45.2%). Most of the patients were vaccinated against Sars-Cov-2 (73.7%), either with two doses (38.0%), three doses (57.0%) or four doses (5.0%) of mRNA-based vaccines. The big majority of the patients (83.3%) were asymptomatic or had mild Covid-19 disease. About half of the patients (53.1%) reported to have received Covid-19 treatment. Thirty-two of them (15.3%) needed hospitalization, and five death cases were reported overall. Among the demographic characteristics, age (p<0.0001 for hospitalization) and comorbidities were associated with worse covid-19 outcomes. In particular, cardiovascular disease (OR 5.37, p=0.001 for covid-19 severity, OR 6.89, p=0.001 for hospitalization), pulmonary disease (OR 3.02, p=0.006 for hospitalization), and obesity (OR 3.46, p=0.044 for hospitalization) had the stronger associations. Non-vaccination status was also associated with a higher risk for hospitalization (OR 2.68, p=0.015). In relation to ARD-related factors, treatment with rituximab (OR 4.11, p=0.002 for hospitalization), systemic sclerosis diagnosis (OR 3.45, p=0.03 for Covid-19 severity) and myositis diagnosis (OR 4.91, p=0.033 for hospitalization) were associated with worse Covid-19 outcomes. On the other hand, spondyloarthropathies appear to be negatively associated with Covid-19 severity (OR=0.27, p=0.035).ConclusionAccording to our study, most ARD patients recovered uneventfully from Covid-19. However, there are several indications that we should be vigilant for patients who remain unvaccinated, are older, have a systemic sclerosis or myositis diagnosis, and/or receive intense immunosuppressive regiments such as rituximab.References[1]Papagoras C, Fragoulis GE, et al. Better outcomes of COVID-19 in vaccinated compared to unvaccinated patients with systemic rheumatic diseases. Ann Rheum Dis. 2021 Nov 10.[2]Strangfeld A, Schäfer M, et al. Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry. Ann Rheum Dis. 2021 Jul;80(7):930-942.Table 1.N=209ARD Diagnosisn (%)Rheumatoid arthritis34 (16.3)Seronegative spondyloarthropathies60 (28.7)Systemic lupus erythematosus45 (21.5)Systemic sclerosis24 (11.5)Sjogren's syndrome15 (7.2)Vasculitis19 (9.1)Myositis9 (4.3)Other3 (1.4)Acknowledgements:NIL.Disclosure of InterestsNone Declared.
ABSTRACT
BackgroundWe have previously reported short term safety of the COVID-19 vaccination in patients with Systemic sclerosis (SSc) but delayed adverse events (ADEs) (occurring >7 days post-vaccination) are poorly characterized in this rare yet vulnerable disease group.ObjectivesWe analyzed delayed COVID-19 vaccine-related ADEs among patients with SSc, other systemic autoimmune and inflammatory disorders (SAIDs) and healthy controls (HC) using data from the ongoing 2nd global COVID-19 Vaccination in Autoimmune Diseases (COVAD-2) study [1].MethodsThe COVAD-2 study was a cross-sectional, patient self-reporting e-survey utilizing an extensively validated, pilot tested questionnaire, translated into 19 languages, circulated by a group of 157 physicians across 106 countries from February to June 2022.We captured data on demographics, SSc/SAID disease characteristics (including skin subset, treatment history and self-reported disease activity), autoimmune and non-autoimmune comorbidities, COVID-19 infection history and course, and vaccination details including delayed ADEs as defined by the CDC.Delayed ADEs were categorized into local injection site pain/soreness;minor and major systemic ADEs, and hospitalizations. We descriptively analyzed the risk factors for overall and specific ADEs in SSc and SAIDs, and further triangulated clinically significant variables in binominal logistic regression analysis with adjustment for age, gender, ethnicity, comorbidity, and immunosuppressive therapy to analyze the survey responses.ResultsFrom among 17 612 respondents, 10 041 patients (median age 51 (18-58) years, 73.4% females, 44.9% Caucasians) vaccinated against COVID-19 at least once (excluding incomplete responses and trial participants) were included for analysis. Of these, 2.6 % (n=258) had SSc, 63.7% other SAIDs, and 33.7% were HCs. BNT162b2 Pfizer (69.4%) was the most administered vaccine, followed by MRNA-1273 Moderna (32.25%) and ChadOx1 nCOV-19 Oxford/AstraZeneca (12.4%) vaccines.Among the patients with SSc, 18.9% reported minor while 8.5% experienced major delayed ADEs, and 4.6% reported hospitalization. These values were comparable to those of the ADEs reported in other SAIDs and HCs. Patients with SSc reported higher frequency of difficulty in breathing than HCs [OR=2.3 (1.0-5.1), p=0.042].Individuals receiving Oxford/AstraZeneca reported more minor ADEs [OR=2.5 (1.0-6.0), p=0.045];whereas patients receiving Moderna were less likely to develop myalgia and body ache [OR=0.1 (0.02-1.0), p=0.047 and OR=0.2 (0.05-1.0), p=0.044 respectively].Patients with diffuse cutaneous SSc experienced minor ADEs and specifically fatigue more frequently [OR=2.1 (1.1-4.4), p=0.036, and OR=3.9 (1.3-11.7), p=0.015] than those with limited cutaneous SSc. Self-reported active disease pre-vaccination did not confer any increased risk of vaccine ADEs in the adjusted analysis. Unlike our previous observations in myositis, autoimmune and non-autoimmune comorbidities did not affect the risk of delayed ADEs in SSc. SSc patients with concomitant myositis reported myalgia [OR=3.4 (1.1-10.7), p=0.035] more frequently, while those with thyroid disorders were more prone to report a higher frequency of joint pain [OR=5.5 (1.5-20.2), p=0.009] and dizziness [OR=5.9 (1.3-27.6), p=0.024] than patients with SSc alone. Patients with SSc-interstitial lung disease did not report increased frequency of ADEs.ConclusionA diagnosis of SSc did not confer a higher risk of delayed post COVID-19 vaccine-related ADEs than other SAIDs and HCs. Diffuse cutaneous phenotype and certain co-existing autoimmune conditions including myositis and thyroid disease can increase the risk of minor ADEs. These patients may benefit from pre-vaccination counselling, close monitoring, and early initiation of appropriate care in the post COVID-19 vaccination period.Reference[1]Fazal ZZ, Sen P, Joshi M, Ravichandran N, Lilleker JB, et al. COVAD survey 2 long-term outcomes: unmet need and protocol. Rheumatol Int 2022 Dec;42(12):2151-2158AcknowledgementsCOVAD Study Team.Disclosure of InterestsBo dana Doskaliuk: None declared, Parikshit Sen: None declared, Mrudula Joshi: None declared, Naveen Ravichandran: None declared, Ai Lyn Tan Speakers bureau: Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB, Consultant of: Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB, Samuel Katsuyuki Shinjo: None declared, Sreoshy Saha: None declared, Nelly Ziade Speakers bureau: Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis,Boehringer Ingelheim, Janssen, and Pierre Fabre, Consultant of: Pfizer, Roche, Abbvie, Eli Lilly,NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, and Pierre Fabre, Grant/research support from: Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, and.Pierre Fabre, Tulika Chatterjee: None declared, Masataka Kuwana: None declared, Johannes Knitza: None declared, Oliver Distler Speakers bureau: 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, iQvia, Horizon, Inventiva, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Prometheus, Redxpharma, Roivant, Sanofi and Topadur, Consultant of: 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, iQvia, Horizon, Inventiva, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Prometheus, Redxpharma, Roivant, Sanofi and Topadur, Grant/research support from: 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, iQvia, Horizon, Inventiva, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Prometheus, Redxpharma, Roivant, Sanofi and Topadur, Rohit Aggarwal Consultant of: Mallinckrodt, Octapharma, CSL Behring, Bristol Myers-Squibb, EMD Serono, Kezar, Pfizer, AstraZeneca, Alexion, Argenx, Boehringer Ingelheim, Corbus, Janssen, Kyverna, Roivant, Merck, Galapagos, Actigraph, Abbvie, Scipher, Horizontal Therapeutics, Teva, Biogen, Beigene, ANI Pharmaceutical, Nuvig, Capella, CabalettaBio, Grant/research support from: Mallinckrodt, Pfizer, Bristol Myers-Squibb, Q32, EMD Serono, Janssen, Boehringer Ingelheim (BI), Ashima Makol: None declared, Latika Gupta: None declared, Vikas Agarwal: None declared.
ABSTRACT
BackgroundPatients with rheumatic diseases are at greater risk of developing serious infections due to dysregulation of the immune system and the use of immunosuppressants1. Therefore, preventing infection is crucial, with vaccination being the most important primary prevention intervention, leading to a lower rate of hospital admissions due to infections. However, vaccine hesitancy among persons with rheumatic diseases is widespread due to concerns regarding the safety of vaccines2.ObjectivesDescribe the frequency of adverse events associated with vaccination in patients with rheumatic diseases.MethodsObservational, descriptive, cross-sectional and retrospective study was carried out in patients with rheumatic diseases from the Rheumatology Department of the Hospital Regional 1° de Octubre ISSSTE, from February to May 2022;it included patients over 18 years of age with an established diagnosis of rheumatic disease who had received a vaccine;the researcher applied the vaccine-associated adverse events survey to those patients who agreed to participate by signing the informed consent. The sample size was of 95 patients. Descriptive statistics and summary measures were employed for analysis. We used the chi-square test or Fisher's exact test (when <5) for the comparative analysis of the frequencies of nominal qualitative variables. P<0.05 was considered significant.ResultsThe survey was applied to 115 patients. 85.2% were women;mean age 57.9 years;61.7% had rheumatoid arthritis (RA), followed by systemic lupus erythematosus (SLE) in 13.9%. 55.6% of the patients were treated with steroids, 52.2% received bDMARDs and 48.7% csDMARDs. Patients received various vaccines, of which the most frequent was the one for COVID-19, with 99.1% of included patients having received at least one dose, followed by influenza in 30.4%. 78% of the patients who received at least one dose of a vaccine against COVID-19 presented ≥1 adverse events. The disease in which the highest frequency of adverse events occurred was RA, without this difference being statistically significant (Table 1). The adverse events according to the type of COVID-19 vaccine were the following: Sputnik-V 80%, Pfizer 76.6% and AstraZeneca 76.1%, without statistically significant difference between vaccine types. The most frequently occurring adverse events were injection site pain (80.1%), headache (30.7%), and fatigue (30.7%);In addition, the main vaccine-associated musculoskeletal symptoms were joint pain, myalgia, and morning joint stiffness (Figure 1), which on most cases improved after a NSAID use. Joint pain was more frequent after the second dose of certain vaccine types.Table 1.Frequency of AE after COVID-19 vaccination in patients according to disease.AE (%)pRA560.790SLE140.326Spondyloarthritis40.068Osteoarthritis60.614ConclusionVaccination-associated AE occurred more frequently than reported in international studies;however, they were not more serious. Providing this information to patients is important to improve vaccine acceptance. In addition, the administration of NSAID after the application of the vaccine could be proposed to reduce the presence of side effects.References[1]Rotondo, Cinzia, et. al. Preliminary Data on Post Market Safety Profiles of COVID 19 Vaccines in Rheumatic Diseases: Assessments on Various Vaccines in Use, Different Rheumatic Disease Subtypes, and Immunosuppressive Therapies: A Two-Centers Study. Vaccines, 2021;9(7):730-440.[2]Furer, Victoria, et. al. 2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis 2020;79:39–52.AcknowledgementsTo the residents and staff at HR 1 Octubre for their help in compilating data.Disclosure of InterestsDaniel Xavier Xibille Friedmann Speakers bureau: GSK, Lilly, UCB, Paid instructor for: GSK, Lilly, UCB, Consultant of: GSK, Lilly, UCB, Vanessa Balderas Reyes: None declared, María Olvera: None declared, María Alcocer León: None declared, ALFREDO ALEXANDRI REYES SALINAS Paid instructor for: Abbvie, Janssen, ovartis, Minerva Rodríguez Falcón: None declared, Sandra Miriam Carrillo Vazquez Speakers bureau: Abbvie, Janssen, UCB, Paid instructor for: Abbvie, Janssen, UCB, Consultant of: Abbvie, Janssen, UCB.
ABSTRACT
BackgroundVaccination against SARS-CoV2 had a critical role in the fight against COVID19 pandemic.A weaker humoral response to COVID19 vaccine has been found in rheumatic patients treated with Rituximab (RTX) or Mycophenolate Mofetil (MMF)[1]. Despite the evidence that anti-SARS-CoV-2 mRNA vaccines can elicit a T-cell response [2], some data show that even the cellular immunity could be impaired in rheumatic patients [3] but COVID19 serology is the only parameter that is feasible to measure in daily practice.Tixagevimab+cilgavimab are two human-derived monoclonal antibodies administered parenterally and authorized by regulatory agencies in February 2022 for pre-exposure prophylaxis (PrEP) against COVID19 from different virus variants in fragile patients.ObjectivesTo demonstrate safety and effectiveness of tixagevimab+cilgavimab.MethodsPatients with autoimmune rheumatic diseases undergoing immunosuppressive treatment with RTX or MMF during the vaccination campaign were enrolled between April and June 2022. All patients must have anti-spike antibody levels below the protective threshold (defined by anti-spike IgG titre <250 BAU/ml) after receiving at least 2 vaccine doses.Patients were monitored with a questionnaire every month about COVID19 symptoms (including respiratory and gastrointestinal symptoms, anosmia and ageusia, skin rash and potential contact with COVID19+ subjects) and were checked for anti-spike and anti-nucleocapside antibodies titres every 2 months for a total of a 6 month follow-up. MMF dose was reduced at 1 g/die at the time of vaccine administration.ResultsFifteen patients were enrolled: 9 participants had a connective tissue disease (CTD;1 dermatomyositis, 3 anti-syntethase syndrome, 4 systemic sclerosis, 1 systemic lupus erythematosus) and 6 had vasculitis (all granulomatosis with polyangiitis). 12 of them received RTX in the preceding 12 months and 3 were taking MMF.About safety, the therapy was very well tolerated and only 4 patients (26%) reported a non-severe adverse event in the 2 weeks following drug administration (2 myalgia, 1 headache, 1 fatigue), none of them requiring hospitalization nor pharmacologic treatment.Regarding effectiveness, 3/15 patients contracted SARS-Cov2 infection (20%) with mild symptoms and no need for hospitalization nor oxygen therapy. Only 1 of them received an antiviral drug (nirmatrelvir+ritonavir). All infected patients had a CTD diagnosis. No significant correlation was observed between the type of rheumatic disease and the risk of infection or response to tixagevimab+cilgavimab.ConclusionNone of our patients developed severe adverse events after tixagevimab+cilgavimab administration and, among the 3 SARS-CoV2 infected patients, none required hospitalization nor oxygen therapy.We conclude that in our experience tixagevimab+cilgavimab is a safe and useful complementary immunization strategy to vaccination for COVID19 prophylaxis.These data will be implemented in a larger study, comprehending various immunocompromised patients from several departments.References[1] Furer et al., Ann Rheum Dis, 2021[2] Mangalakumari et al., Nat Rev Immunol, 2020[3] Picchianti-Diamanti et al., Front Immunol, 2021Charateristic of the cohortIdentificativeAgeDiagnosisRTX/MMFSARS-CoV2 InfectionHospitalizationAntiviral drugs180SScMMF-//270ASSDRTX+nono370ASSDRTX+noyes452GPARTX-//551GPARTX-//649SSc+SSjRTX-//768SScMMF-//847LESRTX-//964ASSDRTX-//1068GPARTX-//1123GPARTX-//1258DMRTX+nono1361SScMMF-//1475GPARTX-//1569GPARTX-//Figure 1.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
ABSTRACT
BackgroundPatients with immune-mediated rheumatic diseases (IMRDs) have been prioritized for COVID-19 vaccination to mitigate the infection severity risks. Patients with rheumatoid arthritis (RA) are at a high risk of severe COVID-19 outcomes, especially those under immunosuppression or with comorbidities associated. However, few studies in the literature assessed the safety and immunogenicity of the COVID-19 heterologous vaccine schedules in patients with RA.ObjectivesEvaluate the safety and immunogenicity of two heterologous vaccine schedules against SARS-CoV-2 in patients with RA.MethodsThese data are from the study "SAFER - Safety and Efficacy on COVID-19 Vaccine in Rheumatic Diseases,” a Brazilian multicentric prospective phase IV study to evaluate COVID-19 vaccine in IMRDs in Brazil. Immunogenicity and adverse events (AEs) in patients with RA of all centers were assessed after two doses of ChAdOx1 plus additional dose of BNT162b2 or after two doses of inactivated SARS-CoV-2 vaccine CoronaVac plus additional dose of BNT162b2. The titers of neutralizing antibodies against the receptor-biding domain of protein spike (S) of SARS-CoV-2 (anti-RBD) were measured by chemiluminescence test after each dose of immunizers. Proportions between groups were compared using the chi-square and Fisher's exact tests for categorical variables. Clinical Disease Activity Index (CDAI) before and after vaccination was assessed using the McNemar test.ResultsA total of 107 patients with RA were include in the study, most of them female, with a mean age of 46 years. Biological disease modifying anti-rheumatic drugs (DMARDs) were used by 50 % of the patients and conventional synthetics DMARDs in 48 %. Two doses of CoronaVac plus additional dose of BNT162b2 was used in 66 patients and two doses of ChAdOx1 plus additional dose of BNT162b2 in 41. Only mild AEs were observed, mainly after the first dose. The most common AEs after all doses, regardless of the immunizer type, were pain at the injection, headache, arthralgia and myalgia. ChAdOx1 had a higher frequency of pain at the injection (66% vs 32 %, p < 0,001) and arthralgia (68% vs 15%, p < 0,001) compared to CoronaVac. No patients had flare after the vaccination. The titers of anti-RBD after two doses of ChAdOx1 were higher compared to two doses of CoronaVac (6,03 BAU/mL vs 4,67 BAU/mL, p < 0,001). However, after the additional dose of BNT162b2, the anti-RBD titers were similar in both groups (7.28 BAU/mL vs 7.06 BAU/mL, p = 0.56). Only two cases of COVID 19, with mild symptoms, were reported, one in each group.Figure 1.ConclusionChAdOx1, CoronaVac, and BNT162b2 vaccines are safe in RA patients. The frequency of local adverse effects, particularly pain at the injection site, is high. AEs are more frequent with ChAdOx1, especially after the first dose. The use of the immunizers does not change the degree of inflammatory activity of the disease. The immunogenicity of the two heterologous regimens analyzed was similar.References[1]Marques C, Kakehasi AM, Gomides APM, Paiva EDS, Dos Reis Neto ET, Pileggi GCS, et al. A Brazilian Cohort of Patients With Immuno-Mediated Chronic Inflammatory Diseases Infected by SARS-CoV-2 (ReumaCoV-Brasil Registry): Protocol for a Prospective, Observational Study. JMIR Res Protoc.[2]Medeiros-Ribeiro AC, Aikawa NE, Saad CGS, Yuki EFN, Pedrosa T, Fusco SRG, et al. Immunogenicity and safety of the CoronaVac inactivated vaccine in patients with autoimmune rheumatic diseases: a phase 4 trial. Nat Med. 2021;27(10):1744-1751.[3]Machado PM, Lawson-Tovey S, Strangfeld A, Mateus EF, Hyrich KL, Gossec L, et al. Safety of vaccination against SARS-CoV-2 in people with rheumatic and musculoskeletal diseases: results from the EULAR Coronavirus Vaccine (COVAX) physician-reported registry. Ann Rheum Dis. 2022;81(5):695-709.[4]Tavares ACFMG, Melo AKG, Cruz VA, Souza VA, Carvalho JS, Machado KLLL, et al. Guidelines on COVID-19 vaccination in patients with immunemediated rheumatic diseases: a Brazilian Society of Rheumatology task force. Adv Rheumatol. 2022;62:3.Acknowledg ments:NIL.Disclosure of InterestsNone Declared.
ABSTRACT
BackgroundSARS-Cov2 vaccination has been shown to be effective against severe forms of SARS-Cov2 infection. Several studies investigated the humoral and cellular response to SARS-Cov2 vaccines in patients followed for autoimmune and inflammatory diseases under immunosuppressive or immunomodulatory treatments. It has been shown that patients on immunosuppressive or immunomodulatory therapies have a poor humoral response to the vaccine[1]ObjectivesThe aim of our study was to investigate the humoral response in patients under conventional immunosuppressive and biotherapies compared to healthy controls.MethodsPatients followed for immuno-inflammatory diseases under immunosuppressive or immunomodulatory drugs who received at least one dose of anti- SARS-Cov2 vaccines were included. Quantitative Anti- SARS-Cov2 antibodies (IgM and IgG assay) VIDAS ® were assessed for all patients. Patients were then compared with healthy controls.ResultsWe enrolled 93 blood samples (63 patients with autoimmune and inflammatory disease and 30 healthy controls), the median age was 52 years [Q1 43, Q3 56]. The immuno-inflammatory diseases were: Crohn's disease (n=28), Rheumatoid arthritis (n=9), Hemorrhagic rectocolitis (n=5), Behçet's disease (n=5), Systemic lupus erythematosus (n=4), Sjogren's syndrome (n=3), Sarcoidosis (n=2), Takayasu disease (n=1). All patients continued their treatment during and after vaccination. Nineteen patients were on biotherapies: Infliximab (n=12), Adalimumab (n=3), etanercept (n=2), Ustekinumab (n=1), tocilizimab (n=1). Forty-three patients were on conventional immunosuppressive: azathioprine (n=18), methotrexate (n=16), corticosteroids > 10 mg/d (n=12). All patients had received at least one dose of vaccine: the median number of doses in both groups was 2[1-4] with no statistically significant difference between the 2 groups (p=0.2). The vaccines received in the group of patients were mRNA vaccine (n=35) and other type of vaccine (n=28). In the healthy control group, type of vaccine were mRNA (n=13) other type vaccine (n=17). The patient had a lower mean level of Ig G against SARS-Cov2 antibodies (24.64 IU +/- 16.65) comparing to healthy controls (33.05+/- 10) with statically significant difference (p= 0.014). No difference between the 2 groups was noted in Ig G levels according to the history of SARS-Cov2 infection. No difference was found between conventional immunosuppressive drugs and biotherapies regarding to the level of antibodies.ConclusionOur study highlights that patients with autoimmune disease and under immunosuppressive therapy displayed a decrease of humoral response comparing to healthy controls. This finding was reported in several studies, Geisen et al[2] reported that patients with chronic inflammatory condition and receiving TNF alfa blockers had a decreased protection and a low level Ig A against spike. Based on these data, patients with autoimmune and inflammatory diseases have decreased humoral immunity to SARS-Cov2 and should be encouraged to receive a booster dose of SARS-COv2 vaccine.References[1]Prendecki M, Clarke C, Edwards H, et al. Humoral and T-cell responses to SARS-CoV-2 vaccination in patients receiving immunosuppression. Ann Rheum Dis 2021;80:1322–9. doi:10.1136/annrheumdis-2021-220626[2]Geisen UM, Sümbül M, Tran F, et al. Humoral protection to SARS-CoV2 declines faster in patients on TNF alpha blocking therapies. RMD Open 2021;7:e002008. doi:10.1136/rmdopen-2021-002008AcknowledgementsMrs Hajer Mediouni.Disclosure of InterestsNone Declared.