Is Response to Allergy Immunotherapy Predictable?

Gary Stadtmauer, MD


May 19, 2017


Allergen immunotherapy (AIT) has been around for over 100 years, and plenty of advances have occurred since the first report of successful grass pollen immunotherapy in 1911.[1] Several studies and meta-analyses support the efficacy of both subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) for allergic rhinitis and asthma.[2]

One of the great advantages of AIT is that this immunomodulatory treatment may have an enduring benefit long after AIT is discontinued. One of the disadvantages of AIT, however, is that it is not always effective. We have no tools at our disposal to routinely predict response.

Given the commitment of resources, time, and money for doctors, insurers, and patients, a marker for predicting AIT responsiveness is desirable. With the recent focus on personalized medicine, it seems to be the right time to find a strategy for predicting response to AIT.

Improvement in respiratory allergy symptoms correlates with the shift from T-helper 2 to T-helper 1 cytokine profiles and from immunoglobulin E (IgE) blocking by immunoglobulin G4 antibodies.[1] Even though symptoms may improve early on during the course of AIT, immunologic changes and maximal improvement do not often occur until the second year of AIT.

Predicting Response to AIT

A few trials have looked at factors differentiating AIT responders. One study[4] looking at predictors of response to AIT in children with allergic rhinitis and asthma identified four factors associated with lack of clinical response to hyposensitization to dust mites. Patients who did not respond to dust mite AIT had early tobacco smoke exposure, atopic family history, total serum IgE levels ≥ 965 kU/L, and/or specific IgE/total IgE ratio ≥ 6%.

Another study found that AIT was substantially more successful at alleviating aeroallergen-induced rhinitis and asthma in children with daily farm animal exposure.[5] Farm animal exposure in itself appears to be very effective at primary prevention of atopy and asthma.


There may never be a simple test that adequately predicts response to AIT. Of course, probably the biggest reason for AIT failure is noncompliance with the AIT schedule. In my practice, we try to enhance compliance through an accelerated AIT schedule.

Failure to respond to a completed course of AIT is a big disappointment for patients and physicians. I have been fortunate that it's happened only on rare occasions in my practice (I could count them on one hand). In large part, I believe that is because I routinely perform nasal endoscopy and laryngoscopy. Many sensitized patients have chronic sinusitis, nasal polyps, or reflux as the underlying cause of their symptoms and will not necessarily benefit from AIT. If you have not been trained, the annual endoscopy courses at the American College of Allergy, Asthma, and Immunology and American Academy of Allergy, Asthma, and Immunology will supplement your knowledge.

If you do not "scope" in your practice, here are some ways you can probably improve your odds of AIT success.

  1. Select your patient carefully. If the primary symptom is postnasal drip, think about "silent" reflux or chronic sinusitis.

  2. If the patient has an "allergic cough" that only responds to a sedating antihistamine (eg, chlorpheniramine), then it's quite possible that the problem is not allergy, but the upper airway cough syndrome.

  3. Unless a patient with known nasal polyposis has been optimized medically and surgically, don't expect AIT to be of much benefit.


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