Vaccination in persons with systemic lupus erythematosus: the current state of the problem

Vaccination plays an important role in the prevention of infectious diseases in patients with immunoinflammatory diseases. When vaccinating patients with systemic lupus erythematosus (SLE), as with other immunoinflammatory rheumatic diseases, its safety is of great importance, including mitigating the risks of the primary disease or the development of new autoimmune phenomena. Many practitioners continue to consider autoimmune diseases as a contraindication for vaccination due to the perceived possibility of their exacerbation and reduced vaccine effectiveness during active immunosuppressive therapy.

The lecture presents current data on the immunogenicity, efficacy and safety of vaccines against a number of infections caused by influenza viruses, hepatitis B, Herpes zoster, human papilloma viruses, COVID-19 and pneumococcus in patients with SLE. It has been shown that the benefits of vaccination in patients with SLE significantly outweigh the risk of adverse events or exacerbations of the disease. At the same time, it was noted that the problem of vaccination of such patients requires further study.

1. Solovyev SK, Aseeva EA, Popkova TV, et al. Systemic lupus erythematosus: new horizons for diagnosis and therapy. Nauchno-Prakticheskaya Revmatologiya. 2020;58(1):5-14. (In Russ.).

2. Tsokos GC. Autoimmunity and organ damage in systemic lupus erythematosus. Nat Immunol. 2020 Jun;21(6):605-14. doi: 10.1038/s41590-020-0677-6

3. Bukhanova DV, Belov BS, Tarasova GM, et al. Comorbid infections in rheumatic diseases (according to FSBI RIR named after V.A. Nasonova). Meditsinskii Sovet. 2019;(9):86-91. (in Russ.).

4. Pego-Reigosa JM, Nicholson L, Pooley N, et al. The risk of infections in adult patients with systemic lupus erythematosus: systematic review and meta-analysis. Rheumatology (Oxford). 2021 Jan 5;60(1):60-72. doi: 10.1093/rheumatology/keaa478

5. Edwards CJ, Lian TY, Badsha H, et al. Hospitalization of individuals with systemic lupus erythematosus: characteristics and predictors of outcome. Lupus. 2003;12(9):672-6. doi: 10.1191/0961203303lu452oa.

6. Furer V, Rondaan C, Heijstek MW, et al. 2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis. 2020 Jan;79(1):39-52. doi: 10.1136/annrheumdis-2019-215882 .

7. Fanouriakis A, Kostopoulou M, Alunno A, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis. 2019 Jun; 78(6):736-45. doi: 10.1136/annrheumdis-2019-215089

8. Grimaldi-Bensouda L, Le Guern V, Kone-Paut I, et al. The risk of systemic lupus erythematosus associated with vaccines: an international case-control study. Arthritis Rheumatol. 2014 Jun;66(6):1559-67. doi: 10.1002/art.38429.

9. Geier DA, Geier MR. Quadrivalent human papillomavirus vaccine and autoimmune adverse events: a case-control assessment of the vaccine adverse event reporting system (VAERS) database. Immunol Res. 2017 Feb; 65(1):46-54. doi: 10.1007/s12026-016-8815-9

10. www.vaers.hhs.gov/data/dataguide.html.

11. Vichnin M, Bonanni P, Klein NP, et al. An Overview of Quadrivalent Human Papillomavirus Vaccine Safety: 2006 to 2015. Pediatr Infect Dis J. 2015 Sep;34(9):983-91. doi: 10.1097/INF.0000000000000793

12. GBD 2017 Influenza Collaborators. Mortality, morbidity, and hospitalisations due to influenza lower respiratory tract infections, 2017: an analysis for the Global Burden of Disease Study 2017. Lancet Respir Med. 2019 Jan;7(1):69-89. doi: 10.1016/S2213-2600(18)30496-X

13. Huang Y, Wang H, Wan L, et al. Is Systemic Lupus Erythematosus Associated With a Declined Immunogenicity and Poor Safety of Influenza Vaccination? A Systematic Review and Meta-Analysis. Medicine (Baltimore). 2016 May;95(19):e3637. doi: 10.1097/MD.0000000000003637

14. Puges M, Biscay P, Barnetche T, et al. Immunogenicity and impact on disease activity of influenza and pneumococcal vaccines in systemic lupus erythematosus: a systematic literature review and meta-analysis. Rheumatology (Oxford). 2016 Sep;55(9):1664-72. doi: 10.1093/rheumatology/kew211

15. Wiesik-Szewczyk E, Romanowska M, Mielnik P, et al. Anti-influenza vaccination in systemic lupus erythematosus patients: an analysis of specific humoral response and vaccination safety. Clin Rheumatol. 2010 Jun;29(6):605-13. doi: 10.1007/s10067-010-1373-y

16. Luijten RK, Cuppen BV, Bijlsma JW, Derksen RH. Serious infections in systemic lupus erythematosus with a focus on pneumococcal infections. Lupus. 2014 Dec;23(14): 1512-6. doi: 10.1177/0961203314543918

17. Klippel JH, Karsh J, Stahl NI, et al. A controlled study of pneumococcal polysaccharide vaccine in systemic lupus erythematosus. Arthritis Rheum. 1979 Dec;22(12):1321-5. doi: 10.1002/art.1780221201

18. Croft SM, Schiffman G, Snyder E, et al. Specific antibody response after in vivo antigenic stimulation in systemic lupus erythematosus. J Rheumatol. 1984 Apr;11(2):141-6.

19. Battafarano DF, Battafarano NJ, Larsen L, et al. Antigen-specific antibody responses in lupus patients following immunization. Arthritis Rheum. 1998 Oct;41(10):1828-34. doi: 10.1002/1529-0131(199810)41:10<1828::AID-ART15>3.0.CO;2-T

20. Rezende RP, Ribeiro FM, Albuquerque EM, et al. Immunogenicity of pneumococcal polysaccharide vaccine in adult systemic lupus erythematosus patients undergoing immunosuppressive treatment. Lupus. 2016 Oct;25(11):1254-9. doi: 10.1177/0961203316636472

21. Tarasova GM, Belov BS, Cherkasova MV, et al. Immunogenicity, Tolerability, and Clinical Effectiveness of 23-Valent Polysaccharide Pneumococcal Vaccine in Patients with Systemic Lupus Erythematosus. Antibiotiki i Khimioterapiya. 2020; (5-6):35-40. (In Russ.).

22. Centers for Disease Control and Prevention (CDC). Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2012 Oct 12;61(40):816-9.

23. Chuchalin AG, Briko NI, Avdeev SN, et al. Federal Clinical Guidelines on Preventive Vaccination Against Pneumococcal infections in Adults. Pul’monologiya. 2019;29(1):19-34 (In Russ.).

24. Grabar S, Groh M, Bahuaud M, et al. Pneumococcal vaccination in patients with systemic lupus erythematosus: A multicenter placebo-controlled randomized double-blind study. Vaccine. 2017 Sep 5;35(37):4877-85. doi: 10.1016/j.vaccine.2017.07.094

25. Kuruma KA, Borba EF, Lopes MH, et al. Safety and efficacy of hepatitis B vaccine in systemic lupus erythematosus. Lupus. 2007; 16(5):350-4. doi: 10.1177/0961203307078225

26. Agmon-Levin N, Zafrir Y, Paz Z, et al. Ten cases of systemic lupus erythematosus related to hepatitis B vaccine. Lupus. 2009 Nov;18(13):1192-7. doi: 10.1177/0961203309345732

27. Marra F, Parhar K, Huang B, Vadlamudi N. Risk Factors for Herpes Zoster Infection: A Meta-Analysis. Open Forum Infect Dis. 2020 Jan 9;7(1):ofaa005. doi: 10.1093/ofid/ofaa005

28. Kwan A, Rayes HA, Lazova T, et al. Herpes zoster in SLE: prevalence, incidence and risk factors. Lupus Sci Med. 2022 Jan;9(1):e000574. doi: 10.1136/lupus-2021-000574

29. Guthridge JM, Cogman A, Merrill JT, et al. Herpes zoster vaccination in SLE: a pilot study of immunogenicity. J Rheumatol. 2013 Nov;40(11):1875-80. doi: 10.3899/jrheum.130170

30. Klumb EM, Pinto AC, Jesus GR, et al. Are women with lupus at higher risk of HPV infection? Lupus. 2010 Nov;19(13):1485-91. doi: 10.1177/0961203310372952

31. Dhar JP, Essenmacher L, Dhar R, et al. Lack of Uptake of Prophylactic Human Papilloma Virus Vaccine Among Women With Systemic Lupus Erythematosus Seen at a Regional Medical Center. J Clin Rheumatol. 2019 Dec;25(8):348-50. doi: 10.1097/RHU.0000000000000866

32. Geier DA, Geier MR. A case-control study of quadrivalent human papillomavirus vaccine- associated autoimmune adverse events. Clin Rheumatol. 2015 Jul;34(7):1225-31. doi: 10.1007/s10067-014-2846-1

33. Holt HD, Hinkle DM, Falk NS, et al. Human papilloma virus vaccine associated uveitis. Curr Drug Saf. 2014 Mar;9(1):65-8. doi: 10.2174/15748863113086660062

34. Grönlund O, Herweijer E, Sundström K, Arnheim-Dahlström L. Incidence of new-onset autoimmune disease in girls and women with pre-existing autoimmune disease after quadrivalent human papillomavirus vaccination: a cohort study. J Intern Med. 2016 Dec;280(6):618-26. doi: 10.1111/joim.12535

35. Chao C, Klein NP, Velicer CM, et al. Surveillance of autoimmune conditions following routine use of quadrivalent human papillomavirus vaccine. J Intern Med. 2012 Feb;271(2): 193-203. doi: 10.1111/j.1365-2796.2011.02467.x

36. Raiker R, Pakhchanian H, DeYoung C, et al. Short term outcomes of COVID-19 in lupus: Propensity score matched analysis from a nationwide multi-centric research network. J Autoimmun. 2021 Dec; 125:102730. doi: 10.1016/j.jaut.2021.102730

37. Mageau A, Papo T, Ruckly S, et al. Survival after COVID-19-associated organ failure among inpatients with systemic lupus erythematosus in France: a nationwide study. Ann Rheum Dis. 2021 Dec 10;annrheumdis-2021-221599. doi: 10.1136/annrheumdis-2021-221599. Online ahead of print.

38. Izmirly PM, Kim MY, Samanovic M, et al. Evaluation of Immune Response and Disease Status in Systemic Lupus Erythematosus Patients Following SARS-CoV-2 Vaccination. Arthritis Rheumatol. 2022 Feb;74(2):284-94. doi: 10.1002/art.41937

39. Boekel L, Steenhuis M, Hooijberg F, et al. Antibody development after COVID-19 vaccination in patients with autoimmune diseases in the Netherlands: a substudy of data from two prospective cohort studies. Lancet Rheumatol. 2021 Nov;3(11):e778-e788. doi: 10.1016/S2665-9913(21)00222-8

40. 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 Oct; 80(10):1330-8. doi: 10.1136/annrheumdis-2021-220647

41. Tang W, Gartshteyn Y, Ricker E, et al. The Use of COVID-19 Vaccines in Patients with SLE. Curr Rheumatol Rep. 2021 Nov 12; 23(11):79. doi: 10.1007/s11926-021-01046-2

42. Ferri C, Ursini F, Gragnani L, et al. Impaired immunogenicity to COVID-19 vaccines in autoimmune systemic diseases. High prevalence of non-response in different patients' subgroups. J Autoimmun. 2021 Dec;125: 102744. doi: 10.1016/j.jaut.2021.102744

43. Yuki EFN, Borba EF, Pasoto SG, et al. Impact of distinct therapies on antibody response to SARS-CoV-2 vaccine in systemic lupus erythematosus. Arthritis Care Res (Hoboken). 2021 Nov 21. doi: 10.1002/acr.24824. Online ahead of print.

44. Moyon Q, Sterlin D, Miyara M, et al. BNT162b2 vaccine-induced humoral and cellular responses against SARS-CoV-2 variants in systemic lupus erythematosus. Ann Rheum Dis. 2021 Oct 4;annrheumdis-2021-221097. doi: 10.1136/annrheumdis-2021-221097. Online ahead of print.

45. Nasonov EL, Lila AM, Mazurov VI, et al. Coronavirus Disease 2019 (COVID-19) and Immune-mediated Rheumatic Diseases. Recommendations of the Association of Rheumatologists of Russia. Nauchno-prakticheskaya revmatologiya. 2021;59(3):239-54. (In Russ.).

46. Felten R, Kawka L, Dubois M, et al. Tolerance of COVID-19 vaccination in patients with systemic lupus erythematosus: the international VACOLUP study. Lancet Rheumatol. 2021 Sep;3(9):e613-e615. doi: 10.1016/S2665-9913(21)00221-6. Epub 2021 Jul 21.

47. Fornaro M, Venerito V, Iannone F, Cacciapaglia F. Safety profile and low risk of disease relapse after BNT162b2 mRNA SARS-COV-2 vaccination in patients with rare rheumatic diseases. J Rheumatol. 2022 Jan 15;jrheum.210863. doi: 10.3899/jrheum.210863. Online ahead of print.