Glucocorticoid: Major Factor for Reduced Immunogenicity of 2009 Influenza A (H1N1) Vaccine in Patients with Juvenile Autoimmune Rheumatic Disease

Abstract

Objective.To assess the immunogenicity and safety of non-adjuvanted influenza A H1N1/2009 vaccine in patients with juvenile autoimmune rheumatic disease (ARD) and healthy controls, because data are limited to the adult rheumatologic population.Methods.A total of 237 patients with juvenile ARD [juvenile systemic lupus erythematosus (JSLE), juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM), juvenile scleroderma, and vasculitis] and 91 healthy controls were vaccinated. Serology for anti-H1N1 was performed by hemagglutination inhibition assay. Seroprotection rate, seroconversion rate, and factor-increase in geometric mean titer (GMT) were calculated. Adverse events were evaluated.Results.Age was comparable in patients and controls (14.8 ± 3.0 vs 14.6 ± 3.7 years, respectively; p = 0.47). Three weeks after immunization, seroprotection rate (81.4% vs 95.6%; p = 0.0007), seroconversion rate (74.3 vs 95.6%; p < 0.0001), and the factor-increase in GMT (12.9 vs 20.3; p = 0.012) were significantly lower in patients with juvenile ARD versus controls. Subgroup analysis revealed reduced seroconversion rates in JSLE (p < 0.0001), JIA (p = 0.008), JDM (p = 0.025), and vasculitis (p = 0.017). Seroprotection (p < 0.0001) and GMT (p < 0.0001) were decreased only in JSLE. Glucocorticoid use and lymphopenia were associated with lower seroconversion rates (60.4 vs 82.9%; p = 0.0001; and 55.6 vs 77.2%; p = 0.012). Multivariate logistic regression including diseases, lymphopenia, glucocorticoid, and immunosuppressants demonstrated that only glucocorticoid use (p = 0.012) remained significant.Conclusion.This is the largest study to demonstrate a reduced but adequate immune response to H1N1 vaccine in patients with juvenile ARD. It identified current glucocorticoid use as the major factor for decreased antibody production. The short-term safety results support its routine recommendation for patients with juvenile ARD. ClinicalTrials.gov; NCT01151644.

Vaccination in pediatric rheumatic disease—risks and benefits

“…However, some reports contradict these findings. 4,5 In a 2011 study, Dell'Era et al 5 found a decreased rate of seroprotection against influenza vaccine in 30 patients with juvenile idiopathic arthri tis (JIA) who were treated with antiTNF therapy when compared with healthy con trols and patients with JIA who were not on antiTNF therapy. 5 Aikawa and colleagues 4 reported decreased antibody response to the 2009 influenza A-H1N1 vaccine in patients with PRD on cortico steroids regardless of dose.…”

“…Subgroup analysis showed decreased rates of seroconversion in patients with juve nile systemic lupus erythematosus (SLE), JIA, juvenile dermato myositis and vasculi tis, and an associ ation with lymphopenia. 4 In a multivariate logistic regression model, only corticosteroid use remained statistically signifi cant. 4 Of note, none of the patients in this study were on antiTNF therapy, and 84.5% of the patients on corticosteroids had a diagnosis of SLE, which could affect the results of the regression model.…”

“…4 In a multivariate logistic regression model, only corticosteroid use remained statistically signifi cant. 4 Of note, none of the patients in this study were on antiTNF therapy, and 84.5% of the patients on corticosteroids had a diagnosis of SLE, which could affect the results of the regression model. 4 In addition, with regard to the immunogenicity of mono valent 2009 influenza A-H1N1 and seasonal influenza vaccines, Long et al 6 recently reported decreased humoral and cell mediated immune responses to this vaccine in patients with juvenile SLE and pediatric renal transplant recipients as compared with healthy children and pediatric patients with moderatetosevere asthma or sickle cell disease.…”

Immunogenicity and safety of two doses of a non-adjuvanted influenza A H1N1/2009 vaccine in young autoimmune rheumatic diseases patients

“…5 The safety and effectiveness of one dose of influenza A H1N1/ 2009 vaccination has been previously demonstrated in juvenile ARD patients older than 9 years. 6 However, there are no data that focus solely on children younger than 9 years, which is a subgroup that requires two doses of this pandemic influenza vaccine. Therefore, the objectives of this study were to assess the immunogenicity and safety of two doses of non-adjuvanted influenza A H1N1/2009 vaccine in juvenile ARD patients younger than 9 years old as well as to evaluate the influence of demographic characteristics, leukocyte and lymphocyte counts and immunosuppressive treatments on the vaccine humoral response.…”

Relapse of Systemic Juvenile Idiopathic Arthritis after Influenza Vaccination in a Patient Receiving Tocilizumab

“…Furthermore, reports have shown that there is no increase in disease activity after vaccination, and researchers concluded that patients with these diseases can therefore undergo influenza vaccination (1)(2)(3)5).…”