Effect of time interval and immunosuppressive treatment on durability of humoral immune response in rheumatoid arthritis patients following COVID-19 vaccination

Semiyan Muhamad Ali; Sanaa  Gadbaan Hama

doi:10.15218/zjms.2025.007

Authors

Semiyan Muhamad Ali Department of Clinical Analysis-Clinical biochemistry, College of Pharmacy, Hawler Medical University, Erbil, Iraq.
Sanaa Gadbaan Hama Department of Clinical Analysis-Clinical biochemistry, College of Pharmacy, Hawler Medical University, Erbil, Iraq.

DOI:

https://doi.org/10.15218/zjms.2025.007

Keywords:

Humoral immune response, COVID-19 vaccine, Durability, Immunogenicity, Rheumatic disease

Abstract

Background and objective: The durability of humoral immune response for medium term period of COVID-19 vaccines in Rheumatoid arthritis patients and the role of immunosuppressive treatment have not been yet well investigated. Therefore, we aimed to evaluate the influence of time and immunosuppressive medications on the vaccine efficiency in rheumatoid arthritis patients compare to controls.

Methods: This case control study was conducted from November 2021 to January 2023 included one hundred thirty-one subjects, divided into four groups; where the first group consist of (n=49) unvaccinated rheumatoid arthritis patients, while the second group consist of (n=34), vaccinated rheumatoid arthritis patients, compared with other two group of healthy subjects (n=25 unvaccinated and 23 vaccinated). Blood samples were collected (12 to 16) weeks after the second vaccine dose receipt for measuring serum IgG.

Results: The difference in mean of IgG between the four study groups was non-significant (P = 0.079), the vaccinated rheumatic patients mean IgG 1.43 and 1.65 in vaccinated healthy control. The mean IgG among vaccinated RA patients on biological treatment was 1.70, and higher than non-biological treatment group (1.03). The prevalence of IgG positivity was significantly (P = 0.005) higher among the controls (56.3%) than the Rheumatoid arthritis patients (31.3%), and significantly higher among the vaccinated (50.9%) than the unvaccinated (32.4%) with (P = 0.033). The same pattern observed when the four groups are compared (P = 0.007).

Conclusion: IgG positivity rate obviously decreased mainly in Rheumatoid arthritis groups after medium time interval, with no significant effect for immunosuppressant drugs on vaccination response.

Metrics

Metrics Loading ...

References

Lin Y, Anzaghe M, Schülke S. Update on the Pathomechanism, Diagnosis, and Treatment Options for Rheumatoid Arthritis. Cells. 2020; 9:880. doi: 10.3390/cells9040880.

Ellen M, Gravallese MD, Gary S, Firestein MD. Rheumatoid Arthritis Common Origins, Divergent Mechanisms. N Engl J Med. 2023; 388:529-42. doi: 10.1056/NEJMra2103726.

Wisniewski A, Kirchgesner J, Seksik P, Landman C, Bourrier A, Nion-Larmurier I, et al. Increased incidence of systemic serious viral infections in patients with inflammatory bowel disease associates with active disease and use of thiopurines: United Eur Gastroenterol J. 2020; 8: 303–13. doi: 10.1177/2050640619889763.

Jani M, Barton A, Hyrich K. Prediction of infection risk in rheumatoid arthritis patients treated with biologics: Are we any closer to risk stratification?. Curr Opin Rheumatol. 2019; 31:285–92. doi: 10.1097/BOR.0000000000000598.

Yiu ZZN, Sorbe C, Lunt M, Rustenbach SJ, Kuhl L, Augustin M, et al. Development and validation of a multivariable risk prediction model for serious infection in patients with psoriasis receiving systemic therapy. Br J Dermatol. 2019; 180:894–901. doi: 10.1111/bjd.17421.

Singh JA, Guyatt G, Ogdie A, Gladman DD, Deal C, Deodhar A, et al. American College of Rheumatology/National Psoriasis Foundation guideline for the treatment of psoriatic arthritis. Arthritis Care Res. 2019; 71:2–29. doi: 10.1002/art.40726.

Menter A, Strober BE, Kaplan DH, Kivelevitch D, Prater EF, Stoff, B, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics. J Am Acad Dermatol. 2019; 80:1029–1072. doi: 10.1016/j.jaad.2020.07.087.

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

Farraye FA, Melmed GY, Lichtenstein GR, Kane SV. ACG Clinical Guideline Preventive care in inflammatory bowel disease. Am J Gastroenterol. 2017; 112:241–58. doi: 10.1038/ajg.2016.537.

Rahier JF, Magro F, Abreu C, Armuzzi A, Ben-Horin S, Chowers Y, et al. Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis. 2014; 8:443–68. doi: 10.1016/j.crohns.2013.12.013.

Chakraborty R, Parvez, S. COVID-19: An overview of the current pharmacological interventions, vaccines, and clinical trials. Biochem Pharmacol. 2020; 180: 114184. doi: 10.1016/j.bcp.2020.114184.

Chen WH, Strych U, Hotez PJ, Bottazzi ME. The SARS-CoV-2 vaccine pipeline: An overview. Curr Trop Med Rep. 2020; 7:61–4. doi: 10.1007/s40475-020-00201-6.

Aletaha D, Neogi T, Silman AJ. Rheumatoid arthritis classification criteria an American College of Rheumatology/European League against rheumatism collaborative initiative. Arthritis Rheum. 2010; 2010:2569–81. doi: 10.1002/art.27584.

Nderson J, Caplan L, Yazdany J, Robbins ML, Neogi T, Michaud K, et al. Rheumatoid Arthritis Disease Activity Measures: American College of Rheumatology Recommendations for Use in Clinical Practice. Arthritis Care & Research. 2012; 640-7. doi: 10.1002/acr.21649.

Sorlie DE (ed). Medical biostatistics and epidemiology: Examination and Board review. First ed, 1995, Norwalk, Connecticut, Appleton and Lange:47-88.

Einav G, Levin MD, Lustig Y, Cohen C, Fluss R, Indenbaum V, et al. Waning Immune Humoral Response to BNT162b2 Covid-19 Vaccine over 6 Months. N Engl J Med. 2021; 385:e84. doi: 10.1016/S2213-2600(21)00220-4.

Hua C, Barnetche T, Combe B, Morell J. Effect of methotrexate, anti-tumor necrosis factor and rituximab on the immune response to influenza and pneumococcal vaccines in patients with rheumatoid arthritis: a systematic review and meta-analysis. Arthritis Care Res. 2014; 66:101626. doi: 10.1002/acr.22246.

Fomin I, Caspi D, Levy V. Vaccination against influenza in rheumatoid arthritis: the effect of disease modifying drugs, including TNF alpha blockers: Ann Rheum Dis. 2006; 65:191–4. doi: 10.1136/ard.2007.077461.

Elkayam O, Bashkin A, Mandelboim M. The effect of infliximab and timing of vaccination on the humoral response to influenza vaccination in patients with rheumatoid arthritis and ankylosing spondylitis. Semin Arthritis Rheum. 2010; 39:442–7. doi: 10.1016/j.semarthrit.2008.12.002.

Kivitz AJ, Schechtman J, Texter M. Vaccine responses in patients with rheumatoid arthritis treated with certolizumab pegol.results from a single-blind randomized phase IV trial: J Rheumatol. 2014; 41:648–57. doi:10.3899/jrheum.130945.

Rondaan C, Furer V, Heijstek MW. Efficacy, immunogenicity and safety of vaccination in adult patients with autoimmune inflammatory rheumatic diseases: asystematic literature review for the 2019 update of EULAR recommendations RMD Open. 2019; 5:e001035. doi:10.1136/ rmdopen-2019-001035.

Mori S, Ueki Y, Hirakata N. Impact of tocilizumab therapy on antibody response to influenza vaccine in patients with rheumatoid arthritis. Ann Rheum Dis. 2012; 71:2006–10. doi: 10.1136/annrheumdis-2012-201950.

Tsuru T, Terao K, Murakami M. Immune response to influenza vaccine and pneumococcal polysaccharide vaccine under IL-6 signal inhibition therapy with tocilizumab. Mod Rheumatol. 2014; 24:511–6. doi: 10.3109/14397595.2013.843743.

Kapetanovic MC, Saxne T, Jonsson G. Rituximab and abatacept but not tocilizumab impair antibody response to pneumococcal conjugate vaccine in patients with rheumatoid arthritis. Arthritis Res Ther. 2013; 15:R171. doi: 10.1186/ar4358.

Richi P, Martin MD, de Ory F, Larraya RG, Cava F. Secukinumab does not impair the immunogenic response to the influenza vaccine in patients. RMD Open. 2019; 5:e001018. doi: 10.1136/rmdopen-2019-001018.

Furer V, Zisman D, Kaufman I. Immunogenicity and safety of vaccination against seasonal influenza vaccine in patients with psoriatic arthritis treated with secukinumab. Vaccine. 2020; 38:847–51. doi: 10.1016/j.vaccine.2019.10.081.

Winthrop KL, Silverfield J, Racewicz A. The effect of tofacitinib on pneumococcal and influenza vaccine responses in rheumatoid arthritis. Ann Rheum Dis. 2016; 75:687–95. . doi:10.1136/annrheumdis-2014-207191.

Winthrop KL, Bingham CO, Komocsar WJ. Evaluation of pneumococcal and tetanus vaccine responses in patients with rheumatoid arthritis receiving baricitinib: results from a long-term extension trial substudy. Arthritis Res Ther. 2019; 21:102. doi: 10.1186/s13075-019-1883-1.

Curtis JR, Johnson SR, Anthony DD, Arasaratnam RJ, Baden LR, Bass AR, et al. American College of Rheumatology Guidance for COVID-19 Vaccination in Patients with Rheumatic and Musculoskeletal Diseases. Version 3 Arthritis Rheumatol. 2021; 73:e60–e75.

Terpos E, TrougakosI P, Apostolakou F, Charitaki I, Sklirou A, Mavrianou N, et al. Age-dependent and gender-dependent antibody responses against SARSCoV-2 in health workers and octogenarians after vaccination with the BNT162b2 mRNA vaccine. Am J Hematol. 2021; 96(7):E257-9. doi: 10.1002/ajh.26185.