Immunogenicity, Effectiveness, and Safety of Trivalent Inactivated Influenza Split Vaccine in Patients with Inflammatory Joint Diseases Receiving Modern Antirheumatic Therapy

According to the currently available data from large cohort studies, patients with immuno-inflammatory rheumatic diseases (IIRDs) are at increased risk of infectious complications, including influenza, compared to the general population. Vaccinations are a critical component of their care. However, data on the immunogenicity, efficacy, and safety of influenza vaccines in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) receiving modern anti-rheumatic drugs are limited.

The aim of the study was to investigate the immunogenicity, efficacy, and safety of the trivalent inactivated influenza split vaccine in patients with RA, AS and PsA, observed at the V. A. Nasonova Research Institute.

Materials and methods. The open prospective comparative study included 247 patients: 74 patients with RA, 62 patients with AS, 14 patients with PsA, as well as 97 people without IIRDs who comprised the control group (СG). The patients were selected over six epidemic seasons: 2016–2017, 2017–2018, 2018–2019, 2020–2021, 2021–2022, and 2022–2023. The majority of patients (78,7%) received immunosuppressive therapy at the time of inclusion in the study. The trivalent inactivated influenza split vaccine was administered in an amount of 1 dose (0,5 ml) intramuscularly against the background of anti-rheumatic therapy, regardless of the activity of the main IIRD. The level of class G antibodies to hemagglutinin (HA) of influenza A (H1N1), A (H3N2), and B viruses was determined in optical density units (OD units) using an enzyme-linked immunosorbent assay (PPDP LLC, St. Petersburg) before vaccination, 1–3 and 6 months after vaccination. The clinical efficacy and safety of the trivalent inactivated influenza split vaccine were also evaluated, including the effect on the course of RA, AS, and PsA according to the dynamics of disease activity indices.

Results. After vaccination, a significant increase in the level of antibodies was observed in patients with RA, AS, and PsA. At the second visit after vaccination the level of antibodies, determined in units of optical density, to HA of influenza A (H1N1), A (H3N2) and B was significantly higher compared to baseline values. By the third visit (6 months after vaccination), there was a slight decrease in the immune response, but the level of antibodies remained significantly higher than the initial level for all strains of influenza virus, with the exception of influenza B in the group of patients with RA. During follow-up, influenza or influenza-like illness was absent in 98,6% of patients who completed the study. No negative effect of vaccination on the activity of the underlying IIRD was noted. The frequency of post-vaccination reactions in patients with IIRDs and in the СG was comparable.

Conclusions. The results obtained in the study indicate sufficient immunogenicity, clinical efficacy, and safety of the trivalent inactivated influenza split vaccine in patients with RA, AS, and PsA.

1. Blumentals W.A., Arreglado A., Napalkov P., Toovey S. Rheumatoid arthritis and the incidence of influenza and influenza-related complications: a retrospective cohort study. BMC Musculoskelet Disord. 2012 Aug 27; 13: 158. doi: 10.1186/1471-2474-13-158.

2. Bello S.L., Serafino L., Bonali C., Terlizzi N., Fanizza C., Anecchino C., Lapaldula G. Incidence of influenza-like illness into a cohort of patients affected by chronic inflammatory rheumatism and treated with biological agents. Reumatismo. 2012 Dec 11; 64 (5): 299–306. doi: 10.4081/reumatismo.2012.299.

3. Bower H., Frisell T., Di Giuseppe D., Delcoigne B., Askling J. Influenza outcomes in patients with inflammatory joint diseases and DMARDs: how do they compare to those of COVID-19? Ann Rheum Dis. 2022; 81 (3): 433–439. doi: 10.1136/annrheumdis-2021-221461.

4. Osterholm M.T., Kelley N.S., Sommer A., Belongia E.A. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. Lancet Infect Dis. 2012; 12 (1): 36–44. doi: 10.1016/S1473-3099(11)70295-X.

5. Furer V., Rondaan C., Heijstek M.W., Agmon-Levin N., van Assen S. et al. 2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis. 2020; 79 (1): 39–52. doi: 10.1136/annrheumdis-2019-215882.

6. Bass A.R., Chakravarty E., Akl E.A., Bingham C.O., Calabrese L. et al. 2022 American College of Rheumatology Guideline for Vaccinations in Patients With Rheumatic and Musculoskeletal Diseases. Arthritis Care Res (Hoboken). 2023; 75 (3): 449–464. doi: 10.1002/acr.25045.

7. National Association of Infectious Disease Specialists named after Acad-emician V. I. Pokrovsky, Russian Scientific Society of Therapists Clinical recommendations of the Ministry of Health of the Russian Federation: Influenza in adults. 2022. Elektronnyj resurs — Rezhim dostupa: https: //medi.ru/klinicheskie-rekomendatsii/gripp-u-vzroslyh_27700/. Data obrashcheniya: 23.01.2024. (in Russian)]

8. Friedman M.A., Curtis J.R., Winthrop K.L. Impact of disease-modifying antirheumatic drugs on vaccine immunogenicity in patients with inflammatory rheumatic and musculoskeletal diseases. Ann Rheum Dis. 2021 Oct; 80 (10): 1255–1265. doi: 10.1136/annrheumdis-2021-221244.

9. Park J.K., Lee Y.J., Shin K., Ha Y.J., Lee E.Y., Song Y.W., Choi Y., Winthrop K.L., Lee E.B. Impact of temporary methotrexate discontinuation for 2 weeks on immunogenicity of seasonal influenza vaccination in patients with rheumatoid arthritis: a randomised clinical trial. Ann Rheum Dis. 2018 Jun; 77 (6): 898–904. doi: 10.1136/annrheumdis-2018-213222.

10. Miossi R., Fuller R., Moraes J.C., Ribeiro A.C., Saad C.G., Aikawa N.E., Miraglia J.L., Ishida M.A., Bonfa E., Caleiro M.T. Immunogenicity of influenza H1N1 vaccination in mixed connective tissue disease: effect of disease and therapy. Clinics (Sao Paulo). 2013; 68 (2): 129–34. doi: 10.6061/clinics/2013(02)oa02.

11. Elkayam O., Amir S., Mendelson E., Schwaber M., Grotto I., Wollman J., Arad U., Brill A., Paran D., Levartovsky D., Wigler I., Caspi D., Mandelboim M. Efficacy and safety of vaccination against pandemic 2009 influenza A (H1N1) virus among patients with rheumatic diseases. Arthritis Care Res (Hoboken). 2011 Jul; 63 (7): 1062–7. doi: 10.1002/acr.20465.