Effectiveness and Safety of Vaccination in Patients with Juvenile Idiopathic Arthritis

Background. Vaccination is the most effective method for reducing morbidity, disability, mortality from of various infections. However, there was a view for a long time that vaccines are ineffective and unsafe to use in people with rheumatological diseases, including juvenile idiopathic arthritis (JIA). Objective.

The aim of the study is to analyze literature data on safety and efficacy of vaccination for JIA patients with live and non-live vaccines.

Methods: literature analysis was based on data from medical databases PubMed and Google Scholar.

Results. Both live and non-live vaccines are safe and immunogenic enough for children with JIA. Most studies confirm vaccination efficacy in patients with JIA when using glucocorticosteroids (GCS) and methotrexate, while therapy with disease-modifying antirheumatic drugs (DMARD) can reduce antibody titers over time. In general, antibodies levels preservation in previously vaccinated children with JIA is less than in global population. This indicates the need to administer booster doses for such patients. No adverse effects on the course of primary disease after vaccination and no post-vaccine complications were revealed.

Conclusion. Vaccination of patients with JIA should be performed with reference to the therapy that the patient already receives, under the control of antibodies level. Booster doses should be implemented in case of titers decrease below the protective levels.

1. Ravelli A, Martini A. Juvenile idiopathic arthritis. Lancet. 2007;369(9563):767–778. doi: 10.1016/S0140-6736(07)60363-8

2. Hinks A, Ke X, Barton A, et al. Association of the IL2RA/ CD25 gene with juvenile idiopathic arthritis. Arthritis Rheum. 2009;60(1):251–257. doi: 10.1002/art.24187

3. Yanagimachi M, Miyamae T, Naruto T, et al. Association of HLA-A and HLA-DRB1 with clinical subtypes of juvenile idiopathic arthritis. J Hum Genet. 2011;56(3):196–199. doi: 10.1038/jhg.2010.159

4. Ombrello M, Remmers E, Tachmazidou I, et al. HLA-DRB1*11 and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis. Proc Natl Acad Sci U S A. 2015;112(52):15970–15975. doi: 10.1073/pnas.1520779112

5. Tarp S, Amarilyo G, Foeldvari I, et al. Efficacy and safety of biological agents for systemic juvenile idiopathic arthritis: a systematic review and meta-analysis of randomized trials. Rheumatology (Oxford). 2016;55(4):669–679. doi: 10.1093/rheumatology/kev382

6. Salvana E, Salata R. Infectious complications associated with monoclonal antibodies and related small molecules. Clin Microbiol Rev. 2009;22(2):274–290. doi: 10.1128/CMR.00040-08

7. Atzeni F, Batticciotto A, Masala I, et al. Infections and Biological Therapy in Patients with Rheumatic Diseases. IMAJ. 2016;18(3–4): 164–167.

8. Hurd A, Beukelman Т. Infectious Complications in Juvenile Idiopathic Arthritis Current. Rheumatol Rep. 2013;15(5):327. doi: 10.1007/s11926-013-0327-1

9. Doran MF, Crowson CS, Pond GR, et al. Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study. Arthritis Rheum. 2002;46(9):2287–2293. doi: 10.1002/art.10524

10. Abinun M, Lane JP, Wood M, et al. Infection-Related Death among Persons with Refractory Juvenile Idiopathic Arthritis. Emerg Infect Dis. 2016;22(10):1720–1727. doi: 10.3201/eid2210.151245

11. Harrison P. Antibiotics in Children Increase Risk for Juvenile Arthritis. Medscape Medical News. November 18, 2014. Available online: http://www.medscape.com/viewarticle/835110. Accessed on November 22, 2014.

12. Bongartz T, Sutton A, Sweeting M, et al. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA. 2006;295(19): 2275–2278. doi: 10.1001/jama.295.19.2275

13. Ringold S, Weiss P, Beukelman T, et al. 2013 Update of the 2011 American College of Rheumatology Recommendations for the Treatment of Juvenile Idiopathic Arthritis: Recommendations for the Medical Therapy of Children With Systemic Juvenile Idiopathic Arthritis and Tuberculosis Screening Among Children Receiving Biologic Medications. Arthritis Rheum. 2013;65(10):2499–2512. doi: 10.1002/art.38092

14. Bijl M, Agmon-Levin N, Dayer J, et al. Vaccination of patients with auto-immune inflammatory rheumatic diseases requires careful benefit-risk assessment. Autoimmun Rev. 2012;11:572–576. doi: 10.1016/j.autrev.2011.10.015

15. Namazova-Baranova LS, Valieva SI, Fedoseenko MV, et al. Analysis of the Juvenile Idiopathic Arthritis Immunization Schedule. Pediatricheskaya farmakologiya — Pediatric pharmacology. 2016;13(4):334–339. (In Russ). doi: 10.15690/pf.v13i4.1604

16. Toussirot E, Bereau M. Vaccination and Induction of Autoimmune Diseases. Inflamm Allergy Drug Targets. 2015;14(2):94–98. doi: 10.2174/1871528114666160105113046

17. Groot N, Heijstek M, Wulffraat N. Vaccinations in Paediatric Rheumatology: an Update on Current Developments. Curr Rheumatol Rep. 2015;17:46. doi: 10.1007/s11926-015-0519-y

18. Chalmers D, Scheifele C, Patterson D, Williams R. Immunization of Patients With Rheumatoid Arthritis Against Influenza: A Study of Vaccine Safety and Immunogenicity. J Rheumatol. 1994;21(7): 1203–1206.

19. Koshcheeva YuV, Kharit SM, Chernyaeva TV, et al. Printsipy formirovaniya individual’nogo grafika privivok detyam s revmaticheskimi zabolevaniyami. Nekotorye sovremennye voprosy vaktsinoprofilaktiki. St. Petersburg; 2020. Vol. 2. pp. 27–31. (In Russ).

20. Klotsche J, Niewerth M, Haas J, et al. Long-term safety of etanercept and adalimumab compared to methotrexate in patients with juvenile idiopathic arthritis (JIA). Ann Rheum Dis. 2016;75(5): 855–861. doi: 10.1136/annrheumdis-annrheumdis-2014-206747

21. Horneff G, Seyger MMB, Arikan D, et al. Safety of Adalimumab in Pediatric Patients with Polyarticular Juvenile Idiopathic Arthritis, Enthesitis-Related Arthritis, Psoriasis, and Crohn’s Disease. Pediatr. 2018;201:166–175.e3. doi: 10.1016/j.jpeds.2018.05.042

22. Carvalho L, de Paula F, Silvestre R, et al. Prospective surveillance study of acute respiratory infections, influenza-like illness and seasonal influenza vaccine in a cohort of juvenile idiopathic arthritis patients. Pediatr Rheumatol. 2013;11:10. doi: 10.1186/1546-0096-11-10

23. Kanakoudi-Tsakalidou F, Trachana M, Pratsidou-Gertsi P, et al. Influenza vaccination in children with chronic rheumatic diseases and long-term immunosuppressive therapy. Clin Exp Rheumatol. 2001;19(5):589–594.

24. Woerner A, Sauvain MJ, Aebi C, et al. Immune response to influenza vaccination in children treated with methotrexate or/ and tumor necrosis factor-alpha inhibitors. Human Vaccines. 2011;7(12):1293–1298. doi: 10.4161/hv.7.12.17981

25. DellEra L, Corona F, Daleno C, et al. Immunogenicity, safety and tolerability of MF59-adjuvanted seasonal influenza vaccinein children with juvenile idiopathic arthritis. Vaccine. 2012;30(5): 936–940. doi: 10.1016/j.vaccine.2011.11.083

26. Shinoki T, Hara R, Kaneko U, et al. Safety and response to influenza vaccine in patients with systemic-onset juvenile idiopathic arthritis receiving tocilizumab. Mod Rheumatol. 2012;22(6): 871–876. doi: 10.1007/s10165-012-0595-z

27. Toplak N, Subelj V, Kveder T, et al. Safety and efficacy of influenza vaccination in a prospective longitudinal study of 31 children with juvenile idiopathic arthritis. Clin Exp Rheumatol. 2012;30(3): 436–444.

28. Heijstek M, Ott de Bruina L, Borrow R, et al. Vaccination in paediatric patients with auto-immune rheumatic diseases: A systemic literature review for the European League against Rheumatism evidence-based recommendations. Autoimmun Rev. 2011;11(2):112–122. doi:10.1016/j.autrev.2011.08.010

29. 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;79(1): 39–52. doi: 10.1136/annrheumdis-2019-215882

30. Aikawa NE, Campos LMA, Silva CA, et al. Glucocorticoid: major factor for reduced immunogenicity of 2009 influenza A (H1N1) vaccine in patients with juvenile autoimmune rheumatic disease. J Rheumatol. 2012;39(1):167–173. doi: 10.3899/jrheum.110721

31. Aikawa N, Campos L, Goldenstein-Schainberg C, et al. Effective seroconversion and safety following the pandemic influenza vaccination (anti-H1N1) in patients with juvenile idiopathic arthritis. Rheumatol. 2013;42(1):34–40. doi: 10.3109/03009742.2012.709272

32. Bukhanova DV, Belov BS, Tarasova GM, et al. Efficacy, safety and immunogenicity of a trivalent inactivated split influenza vaccine in patients with rheumatic diseases. Meditsinskiy sovet = Medical Council. 2018;(12):106–110. (In Russ). doi: 10.21518/2079-701X-2018-12-106-110

33. Коstinov МP, Таrasova АА. Vaccination of Children with Rheumatic Diseases. Epidemiology and Vaccinal Prevention. 2016;15(3): 101–105. (In Russ).

34. Kostinov MP, Tarasova AA. Vaktsinoprofilaktika pnevmokokkovoi infektsii i grippa pri autoimmunnykh zabolevaniyakh: A guide for doctors. Moscow: MDV; 2009. 252 p. (In Russ).

35. Kasapcopur O, Cullu F, Kamburoglu-Goksel A, et al. Hepatitis B vaccination in children with juvenile idiopathic arthritis. Ann Rheum Dis. 2004;63(9):1128–1130. doi: 10.1136/ard.2003.013201

36. Nerome Y, Akaike H, Nonaka Y, et al. The safety and effectiveness of HBV vaccination in patients with juvenile idiopathic arthritis controlled by treatment. Mod Rheumatol. 2016;26(3):368–371. doi: 10.3109/14397595.2015.1085608

37. Szczygielska I, Hernik E, Gazda A, et al. Assessment of anti-HBs antibody concentration in children with juvenile idiopathic arthritis treated with biological drugs, vaccinated against viral type B hepatitis in infancy. Reumatologia. 2020;58(1):15–20. doi: 10.5114/reum.2020.93508

38. Maritsi D, Vartzelis G, Soldatou A, et al. Markedly decreased antibody titers against hepatitis B in previously immunised children presenting with juvenile idiopathic arthritis. Clin Exp Rheumatol. 2013;31(6):969–973.

39. Farmaki E, Kanakoudi-Tsakalidou F, Spoulou V, et al. The effect of anti-TNF treatment on the immunogenicity and safety of the 7-valent conjugate pneumococcal vaccine in children with juvenile idiopathic arthritis. Vaccine. 2010;28(31):5109–5113. doi: 10.1016/j.vaccine.2010.03.080

40. Soloshenko MА, Alekseeva EI, Bzarova TМ, et al. Pneumococcal Vaccination of Patients with Juvenile Idiopathic Arthritis: Review of International Experience. Voprosy sovremennoi pediatrii — Current Pediatrics. 2017;16(1):24–28. (In Russ). doi: 10.15690/vsp.v16i1.1691

41. Brunner HI, Tzaribachev N, Cornejo GV, et al. Maintenance of antibody response to diphtheria/tetanus vaccine in patients aged 2–5 years with polyarticular-course juvenile idiopathic arthritis receiving subcutaneous abatacept. Pediatr Rheumatol. 2020;18(1):1–7. doi: 10.1186/s12969-020-0410-x

42. Heijstek М, van Gageldonk P., Berbers G. Differences in persistence of measles, mumps, rubella, diphtheria and tetanus antibodies between children with rheumatic disease and healthy controls: a retrospective cross-sectional study. Ann Rheum Dis. 2012;71(6):948–954. doi: 10.1136/annrheumdis-2011-200637

43. Borte S, Liebert U, Borte M, Sack U. Efficacy of measles, mumps and rubella revaccination in children with juvenile idiopathic arthritis treated with methotrexate and etanercept. Rheumatology. 2009;48(2):144–148. doi: 10.1093/rheumatology/ken436

44. Heijstek M, Kamphuis S, Armbrust W, et al. Effects of the live attenuated measles mumps-rubella booster vaccination on disease activity in patients with juvenile idiopathic arthritis: a randomized trial. JAMA. 2013;309(23):2449–2456. doi: 10.1001/jama.2013.6768

45. Korematsu S, Miyahara H, Kawano T, et al. A relapse of systemic type juvenile idiopathic arthritis after a rubella vaccination in a patient during a long-term remission period. Vaccine. 2009;27(37): 5041–5042. doi: 10.1016/j.vaccine.2009.06.052

46. Lybimova NA, Fridman IV, Goleva OV, et al. Preservation of Postvaccinal Immunity to Measles, Rubella, Parotitis, Hepatitis B and Diphtheria in Patients With Juvenile Idiopathic Arthritis Who Undergone Planned Immunization Under the Age of Two: Preliminary Results of CrossSectional Study. Voprosy sovremennoi pediatrii — Current Pediatrics. 2019;18(6):435–441. (In Russ). doi: 10.15690/vsp.v18i5.2063

47. Erguven M, Kaya B, Hamzah O, Tufan F. Evaluation of immune response to hepatitis A vaccination and vaccine safety in juvenile idiopathic arthritis. J Chin Med Assoc. 2011;74(5):205–208. doi: 10.1016/j.jcma.2011.03.004

48. Stoof S, Heijstek M, Sijssens K, et al. Kinetics of the longterm antibody response after meningococcal C vaccination in patients with juvenile idiopathic arthritis: a retrospective cohort study. Ann Rheum Dis. 2014;73(4):728–734. doi: 10.1136/annrheumdis-2012-202561

49. Esposito S, Corona F, Barzon L, et al. Immunogenicity, safety and tolerability of a bivalent human papillomavirus vaccine in adolescents with juvenile idiopathic arthritis. Exp Review Vaccines. 2014;13(11):1387–1393. doi: 10.1586/14760584.2014.943195

50. Heijstek M, Scherpenisse M, Groot N, et al. Immunogenicity and safety of the bivalent HPV vaccine in female patients with juvenile idiopathic arthritis: a prospective controlled observational cohort study. Ann Rheum Dis. 2014;73(8):1500–1507. doi: 10.1136/annrheumdis-2013-203429

51. Pileggi G, de Souza C, Ferriani V. Safety and immunogenicity of varicella vaccine in patients with juvenile rheumatic diseases receiving methotrexate and corticosteroids. Arthritis Care Res (Hoboken). 2010;62(7):1034–1039. doi: 10.1002/acr.20183

52. Toplak N, Avčin T. Long-term safety and efficacy of varicella vaccination in children with juvenile idiopathic arthritis treated with biologic therapy. Vaccine. 2015;33(33):4056–4059. doi: 10.1016/j.vaccine.2015.06.086