Immunogenicity and safety of routine vaccines in children and adolescents with rheumatic diseases on immunosuppressive treatment — a systematic review

• Published in: European journal of pediatrics Vol. 181; no. 4; pp. 1329 - 1362
• Main Authors: Keller, Michèle, Pittet, Laure F., Zimmermann, Petra
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2022; Springer Nature B.V
• Subjects: Adolescent; Adolescents; Age differences; Arthritis; Child; Children; Humans; Immunization Schedule; Immunogenicity; Immunosuppressive Agents - adverse effects; Medicine; Medicine & Public Health; Pediatrics; Review; Reviews; Rheumatic diseases; Rheumatic Diseases - drug therapy; Rheumatic Diseases - etiology; Safety; Seroconversion; Systematic review; Systemic lupus erythematosus; Teenagers; Vaccination; Vaccines; Vaccines, Attenuated - adverse effects; Juvenile dermatomyositis; Disease activity; Humoral response; Systemic lupus erythematosus; Juvenile arthritis; Immunisation; Antibodies; DMARD; Juvenile autoimmune rheumatic diseases
• ISSN: 1432-1076; 0340-6199; 1432-1076
• DOI: 10.1007/s00431-021-04283-w

The immunogenicity of vaccines in children with juvenile autoimmune rheumatic diseases (JARDs) can be reduced, there are additional safety concerns around vaccination, and there is a potential for worsening in disease activity. In this systematic review, we summarise studies that investigated the immunogenicity and safety of routine vaccines in children and adolescents with JARD on immunosuppressive treatment. We identified 37 studies investigating 2571 children and adolescents with JARD on immunosuppressive treatment and 4895 control children. Of the 56 geometric mean antibody titres measured, 19 (34%) were lower, six (11%) higher, and 31 (55%) similar; of the 39 seroprotection rates measured, 10 (26%) were lower, two (5%) higher, and 27 (69%) similar; and of the 27 seroconversion rates measured, nine (33%) were lower, two (8%) higher, and 16 (59%) similar in children with JARD on immunosuppressive treatment compared with control children. However, many of the studies were underpowered, and not designed to show non-inferiority between children with JARD and controls. Subgroup analysis for different types of immunosuppressive treatments was not feasible, as most studies did not report results by treatment. Severe adverse events were reported in 38 children (33 with juvenile idiopathic arthritis, four with systemic lupus erythematosus, and one in a healthy child); most of them were likely not related to the vaccination (e.g. elective hospitalisation or surgery). A worsening in disease activity was reported in 44 (2%) children with JARD; again, many of them were likely not related to the vaccination. There were no safety concerns with live attenuated vaccines; however, only few studies reported results for this. Conclusion : Vaccination in children with JARD on immunosuppressive treatment is safe and should be promoted, especially since these children are at increased risk for infection. The importance for the completion of vaccination schedules should be stressed. Strategies to compensate for the lower vaccine responses, which are found in approximately one-third of these children, include measuring antibody levels to determine the optimal timing for the administration of additional booster doses. What is Known: • Children with juvenile autoimmune rheumatic diseases (JARDs) are at higher risk for infections, due to their underlying disease and their immunosuppressive treatment. • In children with JARD, the immunogenicity of vaccines might be reduced, and concerns about safety or the potential for worsening in disease activity after vaccination exist. What is New: • Our systematic review shows that vaccines in children with JARDs on immunosuppressive treatment are safe and immunogenic. • There are several limitations of the currently published studies, including random timing of measuring vaccine responses and age differences between children with JARD and control groups. Many of the studies were underpowered, and not designed to show non-inferiority between children with JARD and controls.