By Dr. Larry Chiaramonte
While Paul and I both have our doubts about sub-lingual immunotherapy [SLIT] as the next big thing in immunotherapy, pharmaceutical companies are putting their money where their tongues are and it will be a force to reckon with for allergists and their patients.
Drops under the tongue have been used outside the United States for at least thirty years, with patients receiving custom liquid mixtures of all their allergens in escalating dosage.
American allergists have been anxious to start using it based on meta-analyses of efficacy done by the Cochrane group because of frustrations with shots. The major roadblock to its wide spread use has been to date the lack of FDA approval. The FDA requires that single antigens be approved, which means that only a minority of US patients can be treated by SLIT, those allergic predominately to one antigen.
In April, three products were approved by the FDA:
FDA approved Oralair®, as the first sublingual immunotherapy tablet for the treatment of grass pollen allergy. Oralair® contains (Sweet Vernal, Orchard, Perennial Rye, Timothy and Kentucky Blue Grass Mixed Pollens Allergenic Extract). Its strength of is expressed in IR (Index of Reactivity). The unit IR has been defined to measure the allergenicity of an allergen extract by Stallergenes and is not comparable to the units used by other allergen manufacturers.
Each sublingual tablet contains either 100 IR or 300 IR, of allergen extract. The recommended maintenance dose and run up dosage adjustment is initiated with a 3-day dose escalation phase, followed by a maintenance treatment with one ORALAIR 300 IR sublingual tablet per day until the end of treatment. The 3-day dose escalation phase consists of: 1 x 100 IR tablet on Day 1, 2 x 100 IR tablet on Day 2, 1 x 300 IR tablet on Day 3 and subsequent days. While this seems to be a rather aggressive dosage escalation, Oralair has been approved and used in more than 31 countries since 2008 with more than 20 million doses given.
Each tablet of Timothy Grass Pollen Allergen Extract contains 2800 Bioequivalent Allergy Units (BAUs), which are units the US allergists use. The usual monthly maintenance dosage now given by allergy injections is 2800 BAUs but it is recommended to be given daily in tablet form. The ratio of SCIT/SLIT dosage would be approximately 1/30, which is in the acceptable ranges. While Grastek® contains a lone allergen and Oralair® contains several, most of the grass pollens share antigens so there should be little advantage to using more than one grass. This would not be true for tree pollen.
The third new product is more interesting to me than the other two. This is called RAGWITEK™, from Merck. As the name suggests, it is for that seasonal nuisance, ragweed. It offers a credible alternative to preseasonal [August/September] shots immunotherapy for ragweed hay fever. It is recommended to be given under the tongue daily starting no later than 12 weeks before the ragweed season [June 1, 2014] CALL YOUR ALLERGIST NOW. The first table is to be taken in the physicians office with the following daily tablets to be given at home with an epinephrine auto-injector nearby.
One reason I like this is that the dosing is relatively short duration compared to three years-plus for either SCIT or SLIT. As I have written previously, long-term compliance with both techniques is a big issue. Not only is twelve weeks a doable regimen, but ragweed season is as annoying an annual event as the shopping season between Thanksgiving and Christmas—although some people do seem to enjoy that.
I am still looking forward to plausible alternatives to immunotherapy. Fortunately, there are some on the not-so-distant horizon, and I plan to write about them in weeks to come.