OP0080 INCIDENCE AND CLINICAL OUTCOME OF COVID-19 RELATED TO POST-VACCINATION ANTIBODY LEVELS IN PATIENTS ON IMMUNOSUPPRESSIVE THERAPY: A PROSPECTIVE STUDY IN THE OMICRON ERA
Hilde S ØrboK. H. BjørlykkeJ. SextonAnne Therese TveterIngrid JyssumIngrid ChristensenGrete Birkeland KroTore K KvienLudvig A. MuntheEspen A. HaavardsholmGunnveig GrødelandSiri MjaalandJohn Torgils VaageK. K. JørgensenSella Aarrestad ProvanSilje Watterdal SyversenG. L. Goll
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Abstract:
Background
Patients with immune mediated inflammatory diseases (IMIDs) on immunosuppressive therapies are known to be at greater risk of severe COVID-19 disease, hospitalisation and death. Protective levels of anti-Spike antibodies following vaccination are yet to be determined.Objectives
To examine whether post-vaccination anti-Spike antibody levels were predictive of breakthrough infection and the clinical outcome of COVID-19.Methods
The Nor-vaC study is a prospective cohort study that includes IMID patients on immunosuppressive therapies[1]. In the present analyses we included patients who provided post-vaccination samples and responded to follow-up questionnaires after three vaccine doses. Hospital records and the Norwegian Death Cause Registry provided information on hospital admissions and cause of death. Anti-Spike antibody levels were measured 2 – 4 weeks after vaccination. Analyses were performed using a cox-regression with time running from two weeks post 3rd vaccine dose until COVID-19 or a 4th vaccine dose, adjusting for age, sex, diagnosis, medication and comorbidity, with calendar month as a time varying covariate.Results
A total of 1051 IMID patients (375 rheumatoid arthritis (RA), 148 psoriatic arthritis (PsA), 155 spondyloarthritis (SpA), 215 Crohn's disease (CD), 158 ulcerative colitis (UC)) on immunosuppressive therapies were included in these analyses, median age 56 (IQR 43 – 65), and 586 (56%) female, with an observation period spanning from July 7th 2021 to December 14th 2022. Patients had received either BNT162b2 (61%) or mRNA-1273 (39%) as a 3rd dose. Immunosuppressive medication included TNF inhibitors (TNFi) monoa- (41%) or combination therapyb (23%), methotrexate (16%), interleukin (IL) inhibitorsc (5%), janus kinase (JAK) inhibitorsd (3%), vedolizumab (5%) and other medicatione(2%). During the observation period 265 patients (25%) were registered with COVID-19 after the 3rd vaccine dose. In total, 24 patients had COVID-19 before the Omicron variant became predominant in Norway (1st January 2022). Symptoms of COVID-19 for more than two weeks were reported by 53 patients (20 %). One patient was hospitalised, and no patients died due to COVID-19 during the observation period. A post-vaccination antibody level above 12.000 BAU/ml gave a reduced risk of clinical COVID-19 infection (hazard ratio (HR) 0.56, p=0.007, 95% CI (0.36, 0.85) (Figure 1). Antibody levels above this cut-off were found in 10 % of patients. The presence of comorbidities (HR 1.85, p = 0.001, 95% CI (1.27,2.70)) or UC (HR 1.6, p= 0.001, 95 %CI (1.11, 2.35) increased the risk of breakthrough infections. Post-vaccination anti-Spike antibody levels were not associated with duration of COVID-19 over two weeks.Conclusion
Patients with the highest post-vaccination anti-Spike levels had a lower risk of COVID-19 infection, supporting the role of repeated vaccination in IMID patients on immunosuppressive therapies. These results also underline the good prognosis of Omicron infections in vaccinated IMID patients. Though patients knowing they had low anti-Spike levels may have shielded during periods of high transmission, the absence of severe infections and deaths in this large cohort indicates that low antibody levels did not greatly increase risk of severe COVID-19. aTNF inhibitors: infliximab, etanercept, adalimumab, golimumab, certolizumab pegol. bCombination therapy: methotrexate, sulfasalazine, leflunomide, azathioprine. cIL-inhibitors: tocilizumab, secukinumab. dJAK-inhibitors: filgotinib, baricitinib, upadacitinib, tofacitinib. eOther: abatacept, sulfasalazine, leflunomide, azathioprine.Reference
[1]Syversen S.W et al Arthritis Rheumatol. 2022Acknowledgements
We 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 Interests
Hilde Ørbo: None declared, Kristin Hammersbøen Bjørlykke Speakers bureau: Janssen-Cilag, Joseph Sexton: None declared, Anne Therese Tveter: None declared, Ingrid Jyssum: None declared, Ingrid E. Christensen: None declared, 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, Espen A Haavardsholm Speakers bureau: Pfizer, UCB, Consultant of: AbbVie, Boehringer-Ingelheim, Eli Lilly, Gilead, Gunnveig Grodeland Speakers bureau: Bayer, Sanofi, ThermoFisher, Consultant of: AstraZeneca, Siri Mjaaland: None declared, John Torgils Vaage: None declared, 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.Keywords:
Antibody therapy
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