Sublingual Immunotherapy: Guidance on a Game-Changer in Allergy Treatment

Gary J. Stadtmauer, MD Assistant Professor of Medicine and Clinical Immunology; Staff Physician, Medicine and Clinical Immunology, Mount Sinai School of Medicine, New York, New York May 29, 2014

Sublingual allergen immunotherapy (SLIT) is now FDA approved and commercially available in the United States for treatment of respiratory allergy to Timothy grass and ragweed. This is a milestone event in the management of allergic respiratory disease, presenting more options for treatment. But SLIT also poses challenges for the physicians who treat these allergies. This article will address what SLIT means for patients, primary care physicians, and allergists.

For Patients

For patients, this is only good news. SLIT is ideal for those who would never agree to subcutaneous immunotherapy (SCIT; also known as allergy injections) because of travel schedules, needle phobia, or brevity of seasonal flares. Young children are obvious candidates but so are others who cannot tolerate even minimal symptoms, including singers/actors and outdoor athletes. At the same time, patients will need to keep up with the regimen not only for efficacy but also for safety, and also will need to know when to temporarily stop SLIT (such as during asthma flares).

SLIT Primary Care

SLIT has been around for a long time. It is not quite as effective as SCIT, and although it would seem easier than allergy shots, many patients still do not stick to the regimen. As with SCIT, SLIT is only effective if the appropriate allergens are administered. For example, while Grastek® may hyposensitize patients to Timothy grass and related grasses, it does not crossreact with Bermuda grass. Knowledge of patient sensitivities and exposures, then, is vital.

The therapy must be started a few months before allergy season, when patients are not yet symptomatic, and it also may cause discomfort (oral or gastrointestinal). It’s very important to keep in mind that this is not a drug; it’s an allergen and may induce anaphylaxis. While a patient might think of this as a regular prescription medication, you would never want to just “renew” the drug the way you might an antihistamine. As you read on, you will see that immunotherapy requires careful screening and monitoring.

Guidance for Allergists and Other Clinicians Who May Prescribe Immunotherapy (eg, ENT-Allergists)

Allergists in the United States will now need to acquaint themselves with this new therapy. According to the drug companies, SLIT is contraindicated in patients with moderate to severe asthma or serious medical problems, which is no different from SCIT. The first dose of SLIT should be administered under supervision (in the allergist’s office). The drugs must be started months in advance of allergy season and continued throughout the season. SLIT is also contraindicated in patients with eosinophilic esophagitis (EoE).

These guidelines seem straightforward but raise many questions. For example:

1. Patients can be inconsistent with medication. Is there a higher risk for anaphylaxis in patients who take the tablet intermittently, or for patients who start the tablet with symptom onset during grass or ragweed season as opposed to months earlier, as recommended?

2. There has already been a case report of SLIT-triggered EoE,[1] so will physicians need to caution patients about EoE symptoms? Should we screen all SLIT candidates for EoE symptoms? Which screening questions should prompt referral to a gastroenterologist and delay SLIT initiation?

3. How should we manage SLIT-prescribed patients during an asthma exacerbation (due to upper respiratory infection or allergen exposure)?

A Q&A With an Expert on SCIT and SLIT

I looked for some more answers via email correspondence with Désirée E.S. Larenas Linnemann, MD, who has lectured and published widely on the topic of immunotherapy (both SCIT and SLIT). Here are her responses:

How do you adjust SLIT (or do you withhold it) if a patient has an asthma exacerbation?

Dr. Larenas Linnemann: Just as with SCIT, we withhold, but for a shorter time: We withhold for 3-4 days in case of exacerbation of allergic symptoms [including] marked AR [allergic rhinitis] activation after exposure to allergen or after viral disease, asthma exacerbation, and febrile disease. We then continue with half the dose for 3 days and [then it’s] back to normal again. Also, [use] care after [dental visits and] erosions of the oral mucosa. We suspend treatment until [the dental work is] healed to avoid direct absorption [of the therapy] into the circulation.

How do you move a patient from SLIT to SCIT? Do you have a protocol? I imagine a few scenarios, one in which the response to SLIT is partial. In that case, I would imagine that one might be able to fast-track SCIT.

Dr. Larenas Linnemann: For safety reasons, in my clinic, I [start] from square one when switching SLIT to SCIT, [although updosing would] allow me to reach maintenance in the planned 3 months without delay. I do not fast-track.

Is a nonresponder to SLIT also likely to be a nonresponder to SCIT?

Dr. Larenas Linnemann: If a patient does not experience the desired improvement after 12-18 months of SLIT, we suggest changing to SCIT. For the full effect of SLIT to kick in, it does take quite some time in some cases.

Do you ever see exercise-induced anaphylaxis in SLIT patients that you suspect to be related to the immunotherapy?

Dr. Larenas Linnemann: Never had a case, but we do instruct [patients] to avoid strenuous exercise, preferably [for] 1-2 hours after SLIT. So if the [patient goes regularly] to the gym, it’s better [to administer] SLIT after [going to] the gym.