High Disease Activity: An Independent Factor for Reduced Immunogenicity of the Pandemic Influenza A Vaccine in Patients With Juvenile Systemic Lupus Erythematosus
ClinicalTrials.gov identifier: NCT01151644.
Faculdade de Medicina da Universidade de São Paulo, Reumatologia, Av Dr Arnaldo, 455, 3° Andar, Sala 3105, Sao Paulo, Brazil, 01246-903. E-mail:
Recent findings demonstrated a reduced immunogenicity of the influenza A H1N1/2009 vaccine in juvenile rheumatic diseases. However, a point of concern is whether the vaccine could induce disease flares. The aim of this study was to assess the disease safety of and the possible influence of disease parameters and therapy on nonadjuvant influenza A H1N1 vaccine response of juvenile systemic lupus erythematosus (SLE) patients.
One hundred eighteen juvenile SLE patients and 102 healthy controls of a comparable age were vaccinated. Seroprotection rate, seroconversion rate, and factor increase in geometric mean titer (GMT) were calculated and effective immune response was defined by the Food and Drug Administration and the European Committee for Proprietary Medicinal Products vaccine immunologic standards. Disease parameters, treatment, and adverse events were evaluated.
Age was comparable in juvenile SLE patients and controls (mean ± SD 16.0 ± 3.5 versus 15.9 ± 4.5 years; P = 0.26). Three weeks after immunization, seroprotection rate (73.7% versus 95.1%; P < 0.001), seroconversion rate (63.6% versus 91.2%; P < 0.001), GMT (90.8 versus 273.3; P < 0.001), and factor increase in GMT (8.1 versus 19.9; P < 0.001) were significantly lower in juvenile SLE patients versus controls. Nonseroconversion was associated with a higher frequency of patients with a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score ≥8 (48.8% versus 24%; P = 0.008) and a higher mean ± SD current glucocorticoid dosage (18 ± 21.4 versus 10.5 ± 12.5 mg/day; P = 0.018). Multivariate logistic regression including a SLEDAI-2K score ≥8 revealed that only the SLEDAI-2K remained a significant factor for nonseroconversion (odds ratio 0.42, 95% confidence interval 0.18–0.98; P = 0.045). Disease parameters remained stable throughout the study and no severe vaccine adverse events were observed.
The present study demonstrated adequate disease safety and is the first to discriminate that high disease activity impairs influenza A H1N1/2009 vaccine antibody production in juvenile SLE, in spite of an overall immune response within recommended levels.