Sublingual Immunotherapy for Grass Pollen Allergy Has Long-Lasting Effect
By Jacquelyn K. Beals, PhD
Medscape Medical News
December 16, 2009 (Buenos Aires, Argentina) — A new study shows that sublingual immunotherapy against grass pollen allergy not only provides symptom relief during the period of administration, it also has long-lasting effects on symptom reduction 1 year after completing the course of treatment.
The multinational phase?3 trial, presented here at the World Allergy Organization XXI World Allergy Congress, was a double-blind placebo-controlled trial designed to investigate the effect of grass allergen immunotherapy tablets (Grazax, ALK Abello, Denmark) in treating rhinoconjunctivitis characteristic of hay fever.
The study enrolled patients with moderate to severe grass pollen allergy who were dissatisfied with their previous treatment results. The initial 634 participants were randomly assigned to receive either grass allergy tablet immunotherapy or a placebo once a day for 3 years; 1 year of follow-up has been completed and a second year is ongoing. At the end of the first year, 546 patients were still participating and 351 have continued into the second year. Overall, the study has seen about a 10% drop-out rate each year.
"Patients who dropped out were compared with those who stayed in, and their response to treatment was nearly identical," said Stephen R. Durham, MD, FRCP, head of the section for allergy and clinical immunology at the National Heart and Lung Institute, Imperial College, and professor of allergy and respiratory medicine at Royal Brompton Hospital, in London, United Kingdom, to the audience. "So we're not looking at a responder population."
Patients kept rhinoconjunctivitis symptom records on eye and nose symptoms, with a scoring scale assessed daily during the entire grass pollen season. The scale rates 2 eye symptoms and 4 nasal symptoms on a scale from 0 to 3, with 0 representing absence of symptoms and 3 representing severe symptoms.
A Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) was completed weekly. Grass pollen counts were obtained from 26 sites in Europe to estimate patients' exposure to the grass pollen allergen. Patients were allowed to take symptomatic medications, including oral or eye-drop antihistamines, nasal steroid spray, and oral steroids, as needed throughout the study. Medication use was noted daily throughout the grass pollen season.
"Daily treatment over 3 years was accompanied by an approximate 30% reduction in symptoms and a 40% to 50% reduction in rescue antiallergic drugs during seasonal pollen exposure," Dr. Durham said in correspondence with Medscape Allergy and Immunology.
Of great significance was the persistence of symptom reduction following the 3-year treatment. This reduction "persisted for at least 12 months, with the same benefit during the following season," Dr. Durham noted. "The treatment was well tolerated, with side effects largely confined to itching and swelling in the mouth that resolved within 1 to 2 weeks."
At the end of the fourth year — a year after completing 3 years of grass allergy tablet immunotherapy — rhinoconjunctivitis scores in the treated group were 26% lower than those in the placebo group (P?< .001). Medication scores were 29% lower in the treatment group (P?< .02). The RQLQ scores correlated with exposure to grass pollen, and the overall RQLQ score for the grass pollen season was 23% better (a lower score) in the treatment group than in the placebo group (P?= .004).
During his presentation, Dr. Durham described the challenges of assessing rhinoconjunctivitis scores during a long pollen season in which, at least 40% of the days, little pollen was in the air. His statistician clumped the days into groups of 10, with cumulative total pollen counts. On days when pollen counts were below 10, approximately 70% of patients were asymptomatic, 25% had moderate to mild symptoms, and only 5% had severe symptoms. When pollen counts were high, many more patients showed severe symptoms.
Plotting a combined symptom and medication score against pollen counts showed a clear separation between the treatment and placebo groups. Interestingly, the difference between groups was larger during the third and fourth year of the study. In addition, the difference between the treated and placebo groups became more marked as pollen counts increased.
"Allergen immunotherapy is effective in patients with severe hay fever," Dr. Durham told Medscape Allergy and Immunology. "For the first time, we provide convincing evidence that grass tablet immunotherapy via the sublingual route results in a long-lasting effect."
The advantages of sublingual immunotherapy were further explained by session comoderator Lars Jacobsen, MSc, director of Allergy Learning and Consulting in Copenhagen, Denmark. "The advantage of the sublingual immunotherapy is that?.?.?. the drug that is used for sublingual immunotherapy carries a safety profile that allows for home treatment.?.?.?. Injection therapy has to be performed by a qualified doctor in order to avoid potential risk of side effects," he told Medscape Allergy and Immunology.
"As we see now,?.?.?. it seems that we can achieve the same clinical effect [with sublingual immunotherapy as with subcutaneous immunotherapy]. So the advantage of sublingual [immunotherapy] is that you can use it as a home treatment," said Mr. Jacobsen. "The disadvantage is that you [have to take] the drug every day, whereas with the shots, you [only have to get] to the doctor every 8 weeks to get the injection."
"It has been shown, with subcutaneous immunotherapy, that there's a long-term effect," noted Mr. Jacobsen. "This is the first time that we can show that sublingual immunotherapy seems to carry the same benefit as injected immunotherapy in the long term."
Dr. Durham reports receiving research funding and lecture and consultancy fees from ALK Abello, a manufacturer of allergy vaccines. Mr. Jacobsen reports that he was a codesigner on the SQ tablet project.
World Allergy Organization XXI World Allergy Congress (WAC): Abstract?914. Presented December?9, 2009.
