March 5, 2010 (New Orleans, Louisiana) — A grass allergy immunotherapy tablet (AIT) given before and during pollen season is safe and clinically effective in children with allergic rhinoconjunctivitis (ARC) to timothy grass, according to results from a new randomized study.
Although this has been proven in recent European studies, "this was the first successful phase 3 trial in North America to investigate AIT in children," said Jennifer Maloney, MD, associate director and allergist in the research division of Merck & Company in Kenilworth, New Jersey, during a late-breaking abstract session here at the American Academy of Allergy, Asthma and Immunology 2010 Annual Meeting.
She reported that almost 27% of the US population between the ages of 6 and 74 years has had positive skin test responses to grass pollen.
"So there is a real need for therapy for these patients, and I believe that the grass AIT may become a new therapeutic modality for children with grass pollen allergy," Dr. Maloney told Medscape Allergy and Clinical Immunology.
Symptoms, Medication Use Decrease With AIT
A total of 345 children (5-17 years of age) with grass pollen ARC were enrolled throughout 2008 at centers in the United States and Canada and randomized to receive either once-daily grass AIT (n = 175; 67% male; 87% white; 87% multisensitized; mean age, 12.1 years) or placebo (n = 170; 62% male; 88% white; 91% multisensitized; mean age, 12.6 years) 16 weeks before the 2009 grass pollen season. All patients were receiving treatment for approximately 23 weeks and used daily electronic diaries to record symptoms and the use of any rescue medications.
The total combined daily symptom score (DSS) and daily medication score (DMS) during the entire season were the primary efficacy endpoints, whereas secondary endpoints included the individual DSS and DMS from the Juniper Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), IgG4 levels, and IgE-blocking factors.
The mean pollen season in 2009 was 43 days at the study sites, and the mean grass pollen count was 28 grains/cm3.
"It was a mild season, but there were enough children who developed symptoms for us to be able to detect significant differences," explained Dr. Maloney.
Results showed a significantly improved total combined score, with a 26% reduction, for the patients treated with the AIT compared with those treated with the placebo (P = .001).
The AIT group also showed reductions in mean individual DSS (by 25%, P = .002) and in DMS (66%, P = .006) and improved RQLQ scores (with a reduction of 18%; mean difference, 0.32; P = .028) compared with the placebo group.
"The DMS reduction may be a little misleading because we were looking at such low numbers," reported Dr. Maloney. "There was very little use of the rescue medication, which could be due to the very mild season."
There was also an approximate 3-fold increase in IgG4 levels and a nearly 5-fold increase in IgE-blocking factors in the AIT-treated patients compared with the placebo-treated patients.
Finally, "the majority of treatment-related adverse events for the AIT were local and nonsevere reactions, with no reports of anaphylaxis," reported Dr. Maloney.
The most common events included oral pruritus (38.9% vs 3.6% for the AIT and placebo groups), throat irritation (37.1% vs 3%), and stomatitis (14.9% vs 1.2%), whereas throat pain, eye itching, and lip swelling occurred in less than 10% of the AIT patients.
A total of 13 patients in the AIT group and 5 in the placebo group discontinued study participation because of treatment-related adverse effects.
"The main takeaway from this study is that we were able to demonstrate a very nice effect in a North American population and that has been a big criticism. Many people were thinking it wouldn't work here, where many subjects are multisensitized," said Dr. Maloney after the presentation.
"Although the timothy grass AIT was shown to be effective, we're not at the point yet to recommend its use to clinicians. However, I think it's something to look at," she concluded. "It's not approved at this point, but it is something to keep an eye on."
The investigators are currently assessing the drug's safety and effectiveness in adults.
Encouraging First Step in the United States
"Oral AIT is relatively standard in Europe; so it's nice to see that we can duplicate the results here in the United States," said session moderator Jonathan M. Spergel, MD, PhD, associate professor of pediatrics at Children's Hospital of Philadelphia, Pennsylvania.
However, "I worry about the number of discontinuations and wonder if there will be a significant number of patients who will decide that the side effects are too much to stay on this medication," said Dr. Spergel, who was not involved with the study. "That's the negative. The positive is that it's going to provide another immunotherapy option for our patients."
He added, "The big thing we're going to have to see will be long-term effects. With standard subcutaneous immunotherapy, you take it for a year and then you're protected after that. Does that happen with this drug? We don't have that data yet, but I would say that this is certainly an encouraging first step."
This study was supported by Schering Corp, a division of Merck & Co. Dr. Maloney is an employee of Merck. Dr. Spergel has disclosed no relevant financial relationships.
American Academy of Allergy, Asthma and Immunology (AAAAI) 2010 Annual Meeting: Abstract L10. Presented March 2, 2010.
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Cite this: Grass Allergy Tablet Effective, Relatively Well Tolerated in Children - Medscape - Mar 05, 2010.
