Sublingual immunotherapy effective for young children with allergic rhinitis
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Key takeaways:
- Researchers called this the first study among children aged 1 to 4 years.
- The treatment group saw improved medication and sleep disorder scores.
- Mild adverse reactions occurred with 1.1% of doses.
Sublingual immunotherapy for house dust mite allergy improved allergic rhinitis symptoms among children aged 1 to 4 years over 12 months, according to a study published in Pediatric Allergy and Immunology.
This treatment also induced immunologic changes specific to the allergen and was well tolerated, Koki Sasamoto, PhD, department of allergy, Clinical Research Center for Allergy and Rheumatology, NHO Sagamihara National Hospital, and colleagues wrote.
“The motivation for this study was to find out whether sublingual immunotherapy (SLIT) of mites, which is generally available in Japan from the age of 5, could be realized at a younger age and whether it would be effective clinically and immunologically,” Sasamoto told Healio.
“We also wondered if fundamental treatment of mites, a major cause in allergic asthma, from an early age could help prevent future onset of asthma and improve wheezing,” he continued.
The single-center, nonrandomized, controlled, open-label, prospective clinical study involved 22 children in the treatment group (median age, 41 months) and 12 in the control group (median age, 34 months).
At baseline, both groups had a median baseline allergic rhinitis symptom score of 4 points. Median Dermatophagoides farinae-specific IgE levels included 60.7 kUA/L for the treatment group and 75.2 kUA/L for the control group.
The children in the treatment group began SLIT with a dose of 3,300 Japanese allergy units (JAU) administered in the hospital.
Sasamoto noted that the use of SLIT in tablet form among children aged 1 and 2 years, with careful guidance, was a new finding.
Caregivers administered daily doses of 3,300 JAU at home for 1 week. Doses then increased to 10,000 JAU, which the researchers said was equivalent to 6 standardized quality house dust mite (SQ HDM) units in the United States, under physician supervision at the hospital. Home administration of the HDM sublingual immunotherapy tablet followed daily for 12 months.
The median allergic rhinitis symptom score fell from 4 (interquartile range [IQR], 3-5) at baseline to 3 (IQR, 1-3; P = .002) at 12 months for the treatment group. But in the control group, the median allergic rhinitis symptom score rose from 4 to 6 (IQR, 4-7.3). The researchers called the difference between the groups at 12 months significant (P = .01).
The treatment group also experienced a significant decrease in median medication score, falling from 3 (IQR, 0-7) at baseline to 0 (IQR, 0-2.25; P = .03) at 12 months. The median medication score remained unchanged for the control group.
Similarly, the researchers called the decrease in median sleep disorder score from 3.5 (IQR, 1-6) at baseline to 2 (IQR, 1-3) at 12 months in the treatment group significant (P = .01), but the increase in this score from 0.5 (IQR, 0-2.75) to 2.5 (IQR, 0-5.5) for the control group was not statistically significant.
During the study period, 1.7% of the treatment group and control group alike developed a common cold. Also, 0.3% of the treatment group and 0.7% of the control group experienced a wheezing episode, which the researchers considered a significant difference (P = .005).
There were 72 adverse reactions (1.1%) with 6,401 sublingual immunotherapy doses among eight members of the treatment group. The researchers categorized these reactions as mild. The most common reactions included oral pruritis and discomfort, tongue pruritis and discomfort, skin pruritis and sneezing. There were no cases of anaphylaxis.
“The safety and feasibility of SLIT at such a young age as in this study was a major problem, but we were able to perform it without more severe adverse reactions than SLIT for school-aged children and older,” Sasamoto said.
There was a significant increase in the median D. farinae-specific IgE level to 134 at 6 months (P < .001) in the treatment group, but levels then fell back to 77, which the researchers considered baseline level, at 12 months. In the control group, levels increased to 163 at 12 months (P = .01).
The treatment group also saw a significant increase in median D. farinae-specific IgG4 level at 6 months (1.02; P < .001) and at 12 months (0.96; P < .001), but the control group only saw a significant increase at 6 months (0.59; P = .01). The researchers called the differences in levels between the groups at 6 months and 12 months significant (P < .001 for both).
The researchers called the changes in Dermatophagoides pteronyssinus-specific IgE and IgG4 levels during the treatment period similar as well.
Further, the treatment group had statistically significant higher median specific IgE-blocking factor at 12 months compared with baseline (0.22; P < .001) and compared with the control group (–0.04; P < .01), which did not see any significant change in mean specific IgE-block factor during the study period.
The ratio between D. farinae-specific IgG4 and specific IgE significantly increased (P < .001) from baseline through 12 months for the treatment group as well, but not for the control group. The treatment group’s ratio also was statistically significantly higher than the control group’s ratio at 12 months (P = .003).
Finally, there was a significant increase in the number of inhalant allergen sensitization cases among the treatment group at 12 months (P = .007), whereas the control group saw a tendency toward an increase.
These findings led the researchers to conclude that house dust mite sublingual immunotherapy improved allergic rhinitis symptoms in addition to reducing the frequency of wheezing and changed immune systems among children aged 1 to 4 years.
“There have been few studies of SLIT at younger ages,” Sasamoto said. “However, this study demonstrates that when younger patients with allergic rhinitis undergo 1 year of mite SLIT, not only are their clinical symptoms improved, but their specific IgE, IgG4 and IgE-block factor levels are similar to those of school-aged children and adults.”
Overall, the researchers said that allergic rhinitis symptom scores improved by 25% for the treatment group and got worse by 50% for the control group from baseline through 12 months, resembling findings of similar studies of older children.
These results also suggest that treatment could prevent the exacerbation of these symptoms as well as the progression of wheeze to asthma, the researchers continued, although further studies with more participants would be necessary.
“We hope to implement SLIT in many younger children with allergic rhinitis problems and use it in the future to prevent the onset of allergies,” Sasamoto said. “We are currently conducting a multicenter randomized controlled trial in Japan, and we hope to increase the number of cases. In addition, we would like to study the prevention of asthma by conducting SLIT for a long period of time from childhood.”
For more information:
Koki Sasamoto, PhD, can be reached at kohki_sasamoto_0131@yahoo.co.jp.
Perspective
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Michael S. Blaiss, MD, FACAAI, FAAAAI
These findings are not surprising, as we see the same efficacy and safety in the population aged 12 years and older in the United States with the FDA-approved HDM SLIT tablet. Nevertheless, these results are from a small number of subjects that was not randomized and placebo-controlled, so we should understand that it was not a rigorous study.
I have no experience with HDM SLIT in this age group, but there are a few studies with SLIT drops in very young children suggesting efficacy and safety for inhalant and food allergens.
These findings give us more data of the efficacy and safety of SLIT tablets and, hopefully, in the near future, the FDA will approve the HDM SLIT tablet down to the age of 6 years like we already have for timothy grass and ragweed. Many children refuse subcutaneous immunotherapy due to needle-phobia, so having an approved FDA product for HDM would be very beneficial in clinical allergy practice.
Along with getting approval for HDM SLIT tablet down to the age of 6 years and hopefully even a lower age in the U.S., early use of SLIT tablets in children may be beneficial in prevention of new allergic sensitizations and possibly asthma. These would be exciting areas for research.
Perspective
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The findings of this study are significant because they demonstrate the safety and efficacy of HDM SLIT treatment, particularly in a young population aged 1 to 4 years. The positive results in terms of symptom reduction, decreased medication use and favorable immunological changes suggest that early intervention with SLIT could be beneficial for young children with allergic rhinitis. The potential for SLIT to reduce wheezing frequency in this age group is also noteworthy, as it could have implications for preventing asthma development.
Also, the findings are not surprising, in that previous research on SLIT in several age groups has also demonstrated similar findings. As a SLIT subspecialist treating all ages, these findings are generally consistent with my clinical observations. Early treatment intervention does appear to have additional advantages and potential for even greater immunomodulation over time, including intervening in and potentially rerouting the atopic march.
These findings can help more allergists consider utilizing HDM SLIT as a treatment option and early intervention strategy for young children with allergic rhinitis who are sensitized to dust mite, especially those at risk for developing asthma.
The next step in this research should be a larger, randomized controlled trial to hopefully further confirm these findings and evaluate a longer follow-up timeline to assess for other potential long-term benefits (or other long-term adverse effects or safety issues, though the current body of evidence does not suggest safety or adverse effect concerns with longer horizons). The impact of early HDM SLIT intervention specifically on asthma development would be better delineated.
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