Will sublingual immunotherapy (SLIT) ever come to the United States? Very probably, said Ira Finegold, MD, Chief of Allergy, St Luke’s- Roosevelt Hospital Center, and Clinical Professor of Medicine at Columbia University, NY.
“Since we are really on the cusp of a sublingual tablet being approved by the FDA [US Food and Drug Administration]…we have to start thinking about the issues for the practice of sublingual therapy,” Dr Finegold said.
Dr Finegold reminded the audience that immunotherapy is not new; the first paper on it was published in 1911. Nor is it alien to the United States. “To some extent, it’s already here,” he said. Low-dose immunotherapy has been around since the 1930s, but there are still no good studies showing efficacy.
According to a recent study (Amar SM, et al. J Allergy Clin Immunol. 2009; 124:150-156), 5.9% of US allergists are using SLIT but almost 62% said that they were holding off till FDA ap - proval; commercially available extracts are used off-label 80% of the time, and 66% charge the patient directly. A 2010 poll conducted by the Joint Council of Allergy, Asthma and Immunology echoed these findings, showing very similar percentages.
Another barrier is lack of insurance reimbursement, and “cost-effectiveness cannot be assessed until you know what the effective dose is,” Dr Finegold said.
Risk factors for SLIT have not been established either. Based on ongoing studies, certain trends with SLIT are emerging that can be applied to clinical practice, such as:
- SLIT can be used in children with allergic rhinoconjunctivitis and seasonal asthma, especially if they are monosensitive, for a duration of no less than 3 years
- The earlier the treatment, the better the outcome
- Long-term (ie, 3 years of treatment) use appears to result in clinical improvement and accompanying sustained immunologic changes 1 year posttreatment
- SLIT can have a disease-modifying effect.
Based on the evidence, Dr Finegold said, “after 3 years’ treatment, the improvement is there for at least 1 year.”
A minority of studies have not demonstrated efficacy for SLIT, and SLIT’s safety record is not perfect. “There is no doubt that SLIT is safer than SCIT [subcutaneous immuno therapy],” Dr Finegold said. “There have been no reported fatalities with SLIT, nor in the last 2 years with SCIT, although severe systemic reactions can occur.”
Therefore, “It would seem prudent to initiate therapy in a physician’s office,” he said, but the prescribing physician must be knowledgeable in the prevention and treatment of anaphylaxis, and patients should carry an epinephrine self-injector.
“Although I can’t speak for the FDA, and further, the FDA approves a drug based on efficacy and safety, they do not tell us how to practice medicine. So at this point, we have to start thinking about the issues for the practice of sublingual therapy,” Dr Finegold said.
“There are unanswered questions, and actually, I think the role of allergy societies is to start now, and start formulating what, if the FDA approves a tablet, are going to be our recommendations, so that our members can safely and adequately treat their patients,” he said. “In the United States, 5.9% of allergists are doing it now….With an approval of the product, this will greatly increase. In Europe, 45% are doing it.”
US-Based Evidence Lacking
In another session on SLIT, Harold S. Nelson, MD, said that SLIT is effective in pollen-induced seasonal allergic rhinitis using American extracts, although efficacy and dosing must be determined separately for each allergen. More studies are needed, he said, to determine the efficacy of simultaneous administration of multiple allergens. “There’s almost no evidence that has been generated in the United States,” he said. “In fact, there are 3 articles” using American extracts.
The first study (led by David Skoner;), showed reductions in symptom and medication scores in 22% and 26% of patients, respectively, although neither reached significance. “This study suggests that sublingual immunotherapy employing US standardized short ragweed extract as an oral drop preparation at cumulative doses 10 and 100 times those given subcutaneously can reduce symptom/ medication scores in patients with ragweed rhinoconjunctivitis,” Dr Nelson said.
The second study, led by Dr Nelson, involved 1-year use of grass allergen immunotherapy tablets versus placebo, and 16 weeks of SLIT. The mean reduction was “18% for symptoms, 26% for medication,” he said, adding that the 2 studies demonstrate “sublingual immunotherapy employing a timothy pollen tablet…can significantly reduce symptom/medication scores in adults and children with grass-induced rhinoconjunctivitis by 20% and 26%.”
The third study compared SLIT with grass pollen extract in monotherapy versus combination therapy with a multiallergen extract (Amar SM, et al. J Allergy Clin Immunol. 2009;124:150- 156). “Most of the people in the United States are sensitized clinically to multiple aero allergies. So this study was designed to address the question, do multiple allergens work?” he said.
Because of the study’s small size (N = 56), no significant differences were seen between the 2 active treatment groups—SLIT with timothy pollen extract alone and SLIT with timothy pollen extract plus 9 other pollen extracts