Immunotherapy:

Mark E. Reiber, M.D., F. A.C.S., F.A.A.O.A.

History of immunotherapy:
Immunotherapy was first reported in 1911 as repeated injections with pollens to induce tolerance, a “vaccine for allergy”. In general, each allergen to which a person is allergic must be treated individually and a mix is created based on allergy testing. The exception is some antigens are so similar in structure to others that they can elicit tolerance for each other allowing smaller numbers of allergens to be tested and treated.

Allergy “shots” are accepted:
Minor modifications to subcutaneous immunotherapy (SCIT, or allergy shots) have occurred, but it has been the dominant form of therapy in the United States for a century. It’s proven effective for pollens, molds, cats, dogs, dust mites and cockroach antigens for asthma and allergic rhinitis.

How SCIT works:
Ten weekly doses are given, increasing the amount each week. Then a five times stronger mix is made to begin the schedule again.  This continues until a maximum concentration is reached or the patient experiences reactions preventing further advancement.

Once maintenance is reached, the patient gets weekly injections for 3-5 years. If symptom relief is maintained, shots are tapered and discontinued. A majority of patients develop lasting effects, but a small percentage needs to continue shots beyond the five year point.

The downsides to allergy shots:
SCIT is not without risks and disadvantages. Weekly office visits, with a 20 minute wait following injection, can become inconvenient and costly. Rare reactions include local skin reactions, shortness of breath, and even shock. Very rarely, death has been reported, usually in asthmatics. These factors motivate research to find alternative forms of immunotherapy with increased safety and convenience
 
Looking for alternatives- SLIT is born:
As early as 1913, alternatives such as nasal and oral routes were being proposed. Oral therapy includes direct swallow and sublingual (under the tongue) methods (SLIT).   In 1998 the World Health Organization approved both the sublingual and nasal methods as viable alternatives to SCIT.  Nasal delivery proved to be difficult and less accepted. Oral immunotherapy with immediate swallowing is less effective than SLIT. 

SLIT- the basics: 
At ENT Carolina, we offer SLIT and follow the American Academy of Otolaryngic Allergy dosing recommendations. Patients start at a standard concentration and advance over twelve weeks to a maximum strength for one year. If satisfactory response is not seen by a year, therapy is stopped but for the great majority of patients who respond, continue for 3-5 years.  At the end of 5 years, a small percentage require longer therapy, but most develop persistent symptom relief.

How SLIT works: 
It appears the effectiveness of SLIT correlates with the duration of contact with the mouth’s lining. There may be a critical interaction between the immune cells of the floor of the mouth and this effectiveness. It is important to watch the clock to ensure 2 minutes of exposure time. Dosing is performed once daily.
 

Effectiveness of SLIT has been based on reports of symptom decrease and reduced dependency on medications. Duration of at least three years appears necessary for most antigens. Pollen therapy appears most effective with dust mite and pets requiring longer times. We see effects beginning in about six months.

The downsides to SLIT:
Only mild reactions such as oral itching, headache, runny nose, hives, constipation or other gastrointestinal side effects are occasionally seen. To date there have been three episodes of anaphylaxis, and no deaths, associated with SLIT. There have been no reports of anaphylaxis (shock) with inhalant allergens. 

Sublingual immunotherapy is prepared from the same FDA approved antigen extracts used for subcutaneous therapy; however, the FDA has not approved sublingual administration. This is an "off-label" use for allergen extract.  Off-label uses for medications are very common with estimates of 25-50% of all prescriptions being for off-label indications. The studies and review process needed to obtain this approval are underway at this time.  Experience in Europe for over 25 years has demonstrated safety and efficacy. American data is just beginning to become available.

In 2005, the Asthma and Allergy Foundation of America performed a survey of allergy patients that asked for the important features of an allergy medication.  These were the features that were important to 50% or more of the respondents, and how these features relate to SLIT.

So why would someone choose one form of immunotherapy over another?  Subcutaneous immunotherapy is the time tested therapy used for over a century in this country. In addition, insurance companies have generally provided better benefits for SCIT than SLIT.Sublingual immunotherapy is relatively new to the scene, but has proven in over a decade of my experience, to have very positive results. European studies have shown efficacy similar to subcutaneous therapy for several antigens. There is the obvious benefit to a home based, self administered, needle-less therapy. The safety and side effect profiles of SLIT appear superior to SCIT. For many patients, there is not a significant cost difference even with “insurance coverage” so they would just prefer the ease and convenience of “allergy drops”.

7/2009