Background Patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive therapy have an inadequate serologic response following two-dose SARS-CoV-2 vaccination, and a standard vaccination strategy of three doses for this patient group is currently under implementation in several countries. However, the serological response and safety of this strategy has not been evaluated.
Objectives To assess serological response and safety of a three-dose vaccination strategy in IMID patients on immunosuppressive therapy as compared to standard two-dose vaccination of healthy controls.
Methods The prospective observational Nor-vaC study (NCT04798625) enrolled adult patients on immunosuppressive therapy for inflammatory joint- and bowel diseases. Healthy controls were health care workers from participating hospitals. All participants received standard vaccines according to the national vaccination program with three doses in patients and two doses in controls. The third dose was offered to IMID patients >4 weeks after the second dose. Analyses of antibodies binding the receptor-binding domain of the SARS-CoV-2 Spike protein were performed prior to, and 2-4 weeks after the second and third vaccine doses. Levels were compared across groups by Mann-Whitney U tests and multivariate linear regression was used to identify predictors of response.
Results Overall, 961 patients (315 rheumatoid arthritis, 156 spondyloarthritis, 171 psoriatic arthritis, 132 ulcerative colitis and182 Crohn’s disease) (median age 54 years [IQR 43-64]; 56 % women) and 227 controls (median age 44 years [IQR 32-55]; 83 % women) were included in the present analyses. TNFi monotherapy was used by 399 patients, 229 used TNFi in combination with other immunomodulators, 189 methotrexate monotherapy, 39 vedolizumab, 32 JAKi and 73 patients used other drugs. Patients on rituximab were not included. Patients were vaccinated with Pfizer BNT162b2 (54% patients, 14% controls), Moderna mRNA-1273 (16% patients, 40% controls) or a combination of vaccines (30% patients, 46% controls). Patients received the third vaccine dose a median of 120 (IQR 102-143) days after the second dose. After two doses, median anti-Spike antibody levels were significantly lower in patients (861 BAU/ml (IQR 418-4275) than controls (6318 BAU/ml (IQR 2468-9857)), p<0.001 (Figure 1). Following the third dose, patients achieved antibody levels comparable to the two-dose vaccinated controls (median 5480 BAU/ml (IQR 1081-12069), p=0.28) (Figure 1). In the patients anti-Spike antibody levels increased by a median of 2685 BAU/ml (IQR 265-9129) from the second to the third dose. Main factors associated with increased antibody level after the third dose were younger age (β -87.7 (p=0.002)), and vaccine status (mRNA-1273 vaccine (β 5549 (p<0.001)) or a combination of vaccines (β 4367.3 (p<0.001)).
Adverse events were reported by 438 (48%) of patients after the third dose as compared to 471 (54%) after the second dose and 193 (78 %) of controls. Disease flares were reported by 42 (5%) and 69 (8%) patients after the second and third dose, respectively.
Conclusion This study suggests that a third vaccine dose for immunosuppressed patients closes the gap in serological response between patients and the healthy population. Antibody levels following the three-dose regimen in IMID patients were comparable to healthy controls vaccinated twice, and no new safety issues emerged. This finding was consistent across all diagnoses and treatment groups, supporting the implementation of a three-dose vaccine regimen as standard in the IMID population.
Disclosure of Interests Ingrid Jyssum: None declared, Anne Therese Tveter: None declared, Joe Sexton: None declared, Ingrid E. Christensen: None declared, Trung T. Tran: None declared, Siri Mjaaland: None declared, David J Warren: None declared, Tore K. Kvien Speakers bureau: Amgen,Celltrion, Egis, Evapharma, Ewopharma, Hikma, Oktal, Sandoz, Sanofi, Consultant of: Abbvie, Amgen, Biogen, Celltrion, Eli Lilly, Gilead, Mylan, Novartis, Pfizer, Sandoz, Sanofi, Grant/research support from: Grants to institution (Diakonhjemmet Hospital): Abbvie, Amgen, BMS, MSD, Novartis, Pfizer, UCB, Kristin Hammersbøen Bjørlykke: None declared, Grete B. Kro: None declared, Jørgen Jahnsen Speakers bureau: AbbVie, Astro Pharma, Boerhinger Ingelheim, BMS, Celltrion, Ferring, Gilead, Hikma, Janssen Cilag, Meda, MSD, Napp
Pharma, Novartis, Orion Pharma Pfizer, Pharmacosmos, Roche, Takeda, Sandoz, Consultant of: AbbVie, Boerhinger Ingelheim, BMS, Celltrion, Ferring, Gilead, Janssen Cilag MSD, Napp Pharma, Novartis, Orion Pharma, Pfizer, Pharmacosmos, Takeda, Sandoz, Unimedic Pharma, Grant/research support from: Abbvie, Pharmacosmos, Ferring, Ludvig A. Munthe Speakers bureau: Novartis, Cellgene, Espen A Haavardsholm: None declared, John Torgils Vaage: None declared, Gunnveig Grodeland Speakers bureau: Bayer, Sanofi Pasteur, Thermo Fisher, Consultant of: Consulting fees from the Norwegian System of Compensation to Patients and AstraZeneca, Fridtjof Lund-Johansen: None declared, Sella Aarrestad Provan: None declared, Kristin Kaasen Jørgensen Speakers bureau: Roche, BMS, Consultant of: Celltrion, Norgine, Guro Løvik Goll Speakers bureau: AbbVie, Pfizer, UCB, Sandoz, Orion Pharma, Novartis, Consultant of: Pfizer, AbbVie, Silje Watterdal Syversen: None declared
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