PURPOSE OF THE STUDY.
To compare the efficacy and safety of a novel combination of subcutaneous immunotherapy (SCIT) for induction and sublingual immunotherapy (SLIT) for maintenance, to immunotherapy via a single method (either SCIT or SLIT) for both induction and maintenance.
Investigators enrolled 60 children, aged 5 to 12 years, monosensitized to house dust mite (HDM), who had been followed at a pediatric allergy immunology clinic in Istanbul for mild persistent to moderate asthma or rhinitis, with persistent symptoms despite inhaled or intranasal steroids for 2 years.
After an 8-week evaluation to assess baseline symptoms, patients were randomized to 1 of 4 parallel treatment groups. One group was treated with pharmacotherapy, while the other 3 received immunotherapy administered in 1 of the 3 following regimens: (1) 16-week induction with weekly in-clinic SCIT using a glycerinated solution of HDM extract, followed by maintenance with monthly in-clinic SCIT (SCIT alone); (2) 1-month induction with SLIT using extract adsorbed onto aluminum hydroxide, given 3 times per week at home with gradually increasing doses, followed by maintenance at the maximum dose (SLIT alone); or (3) 16-week induction phase using SCIT (described earlier), followed by maintenance with in-home self-administered SLIT (SCIT plus SLIT). During clinic visits at –1, 0, 1, 4, 12, and 18 months, physicians assessed clinical status by recording frequency of asthma attacks, corticosteroid use, symptoms scores, and medications scores. Blood drawn at each of these visits was evaluated for total serum IgE and for HDM-specific levels of IgE and IgG4 antibodies. Additionally, supernatants from culture of peripheral blood mononuclear cells (isolated from whole blood drawn at each visit) were analyzed for HDM-specific interferon (IFN)-γ, transforming growth factor (TGF)-β, interleukin (IL)-5, IL-10, IL-13, and IL-17 cytokines.
Fifty patients completed the study protocol. Immunotherapy for the SCIT alone, SLIT alone, and SCIT plus SLIT groups proved effective in the treatment of asthma and allergic rhinitis. Improved symptoms scores correlated with increases in T-helper 1 (TH1) cytokines (IFN-γ), regulatory T-cell cytokines (TGF-β and IL-10), and ratio of TH1 to TH2 cytokines (IFN-γ/IL-5). For patients in the SCIT alone and SCIT plus SLIT groups, improvement in symptom scores was greater and earlier in onset; this correlated with significant increases in IgG4 levels (blocking antibodies). Interestingly, improvement in scores for allergic rhinitis was only significant in the combined SCIT plus SLIT group. Adverse effects were observed in only 2 patients, both in the SCIT group.
In this prospective, randomized, controlled study, a novel combination of SCIT for induction and SLIT for maintenance was as effective in reducing symptoms as SCIT alone. Additionally, as expected, both SCIT alone and SCIT plus SLIT were found to be more effective that SLIT alone. This combination regimen also had the advantage of allowing patients to receive SLIT in place of SCIT during maintenance phase, thus avoiding the monthly office visits and injections following the initial 16-week induction on SCIT.
While SCIT has been shown to more effective in reducing allergic symptoms than SLIT, SCIT remains unappealing to many pediatric patients because of its poorer safety profile, uncomfortable injections, and in-clinic administration, requiring school absences for patients and work absences for parents. This study offers a promising, novel regimen that will allow patients to avoid the less-appealing aspects of SCIT for the maintenance phase of their course of immunotherapy. Additionally, this study made important conclusions about cytokine responses to immunotherapy and how these correlate with symptoms. Further study should focus on long-term outcomes from this novel regimen to establish its utility in pediatric patients.
- Copyright © 2012 by the American Academy of Pediatrics