Antibody response after varicella vaccination in children treated with budesonide

At present, budesonide inhalation suspension (BIS; Pulmicort® Respules®) is the only inhaled corticosteroid (ICS) approved by the Food and Drug Administration for use in children less than 4 years old requiring treatment for asthma. Children in this age group generally receive a programme of vaccinations against a panel of common childhood illnesses.

ICS and ‘breakthrough’ varicella infection
Concerns remain of the risk for ‘breakthrough’ infection when using live virus vaccination because of the theoretical immunosuppressive action of oral corticosteroids. Similar concerns exist regarding the safety of ICS in this respect, including the possibility of an increased risk of the disease against which the vaccine is intended to offer protection, an increased risk of asthma events or a lack of immune response.

A previous, retrospective study among >88000 asthmatic children aged 12 months to 6 years found an increased risk of ‘breakthrough’ varicella was associated oral corticosteroid prescription in the 3 months following vaccination [1]. However, there was no association with asthma or ICS use among these patients [1].

Asthma therapy and immunogenicity of live varicella vaccine
We performed an open-label, non-randomised, parallel-group study to evaluate the effect of BIS or non-steroidal conventional asthma therapy (NSCAT) on the immunogenicity of a live varicella vaccination among varicella-naïve asthmatic children aged 12 months to 8 years [2]. Children requiring the initiation or continuation of maintenance asthma therapy were eligible for inclusion. The children received daily BIS (0.25–1 mg/day) or NSCAT daily or as-needed for at least 4 weeks prior to vaccination and at least 8 weeks after vaccination. NSCAT consisted of a leukotriene modifier, a cromone or an inhaled β2-agonist selected at the investigator’s discretion.

Blood samples were taken 6 weeks after vaccination to determine antibody levels. A glycoprotein enzyme-linked immunosorbent assay (gpELISA) was used to determine antibody response at baseline and at 6 weeks after vaccination.

Other routine, age-appropriate vaccinations were not permitted during the 4 weeks prior to immunisation and for 6 weeks after immunisation.

Antibody response
We found that a similar proportion of patients achieved a protective level of varicella antibody (≥5 gpELISA units/mL [2]) in each asthma therapy group: 129/151 (85%) in the BIS group and 83/92 (90%) in the NSCAT group; relative risk: 0.95; 95% confidence interval 0.86–1.04 (Table 1). This is comparable with previous reports of the proportion of healthy children who achieve protective antibody levels following live varicella vaccine [3–5].

A previous study found that among 1164 healthy children who received live varicella vaccination those with an antibody titre ≥5 gpELISA units/mL were 3.5 times less likely to develop breakthrough varicella during 7 years follow-up that those children with an antibody titre <5 gpELISA units/mL 6 weeks after vaccination [3].

An evaluation of outcomes for children with antibody titres <5.0 gpELISA units/mL in the study by Li and coworkers [3] found that breakthrough varicella infection was lower among those who seroconverted 6 weeks after vaccination (0.3–4.99 gpELISA units/mL) (15% of converters versus 60% of non-converters). Moreover, the illness tended to be less severe among children who had seroconverted compared with those who had not [3]. Thus, seroconversion may also offer some level of protection against this virus.

In our study, a further 19 patients in the BIS group and 9 patients in the NSCAT were classed as ‘seroconverted’ but not protected as they achieved a level of 1.25–4.9 gpELISA units/mL in the BIS group at 6 weeks post-vaccination (Table 1). These patients were considered eligible for revaccination; a procedure that fell outside the scope of our study.

Table 1: Varicella virus antibody titre at 6 weeks post-vaccination among children (age 12 months to 8 years) receiving concurrent asthma therapy and a baseline titre <5.0 gpELISA units/mL [2].


BIS: budesonide inhaled suspension; NSCAT: non-steroidal conventional asthma therapy


Tolerability and ‘breakthrough’ varicella infection
Overall, we found that the type and intensity of adverse events was similar between the two therapy groups. Adverse events related to varicella vaccination were reported by 8 patients in each treatment group and most commonly consisted of pyrexia, agitation and injection-site reactions. There were no cases of severe varicella in either therapy group. One case of a varicella-like rash was reported in a 12-month-old child who had achieved protective antibody levels in the NSCAT groups 11 days after vaccination; the rash resolved 10 days after its onset.

There were no reports of any serious asthma-related adverse events of discontinuations due to asthma-related adverse events.

Conclusion
We can conclude that response and tolerability of live virus vaccination against varicella among children receiving BIS or NSCAT is comparable. Asthmatic children receiving BIS can be safely and effectively immunised using a live varicella vaccine.