This article is more than 5 years old. Information may no longer be current.

Experts address mechanisms, clinical implications of SLIT agents

SAN DIEGO — During a symposium here, three researchers reported on the therapeutic mechanisms of sublingual immunotherapy, the status of current trials under review by the FDA, and how clinicians can implement their use in practice.

The known mechanisms of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are similar. However, important differences exist, according to a presentation by Stephen R. Durham, MA, MD, FRCP, professor of allergy and respiratory medicine at Imperial College School of Medicine/NHLI and Royal Brompton Hospital London, United Kingdom.

“We have good evidence for dose and time-dependent increases in Ig1, IgG4 and IgA2 antibodies following grass pollen SLIT. Interestingly, and I’ve not shown the data today, but if we look at house dust mites SLIT trials, the data in relation to IgG is not as robust as it is for pollens. Whether this reflects an alternative mechanism, or whether it’s just a dosing effect remains to be seen,” Durham said.

There’s also good evidence that SLIT-induced IgG antibodies are functional, according to Durham. However, there’s also some evidence of suppression of allergen-stimulated T cell proliferation and cytokine production following SLIT, he added.

“There is some evidence for induction of systemic T regulatory cells; although here the data are not totally consistent from different studies, which is perhaps not surprising; these assays are very complex to perform,” Durham said.

Currently, he said, there is no immediate translation of these data in clinical practice in terms of biomarkers.

“My suggestion would be that the induction of an IgG response would be necessary but not necessarily sufficient for clinical efficacy; and certainly in clinical trials, we expect to see a robust IgG response following sublingual treatment,” Durham said.

Agents in the pipeline

It is likely that two grass and one ragweed SLIT tablet products will be approved by the FDA this year, Thomas B. Casale, MD, FAAAAI, of University of South Florida Morsani College of Medicine, said during a presentation here.

One of the grass agents is Grastek (MK7243, Merck), a once-daily sublingual tablet (2,800 BAU) for adults and children with seasonal allergic rhinoconjunctivitis (SARC) due to grass pollen, containing a biologically standardized Timothy grass allergen extract derived from extraction and purification of Phleum pratense pollen, according to Casale.

“For seasonal treatment, the patient should initiate dosing at least 8 weeks before the grass pollen season and continue daily until the end of the grass pollen season,” Casale said.

However, for sustained and disease modifying treatment, Casale recommends the patient take one sublingual tablet daily year-round for three consecutive years.

Another grass agent with potential for approval is Oralair (Stallergenes), according to Casale. The once-daily sublingual tablet is indicated for patients with SARC due to grass pollen. The agent contains an allergen mixture obtained by concurrent extraction from five different grass pollens, including: Kentucky bluegrass, orchard, perennial rye, sweet vernal, and timothy grasses, according to data presented by Casale.

The third agent in the pipeline is Ragwitek (Merck), a once-daily sublingual tablet for patients with SARC due to ragweed pollen.

Among all three agents, efficacy was similar to SCIT regardless of individual patient profiles, according to Casale. Each required 8 to 16-week preseason treatments. However, safety appeared better than with SCIT administration, Casale said.

Clinical implications

If approved, the first dose of SLIT tablets would be administered in practice, and a prescription for an epinephrine emergency pen would be written for the patient. Subsequently, all other doses would be self-administered by the patient at home, according to Casale.

“Clearly, the most important adverse events that happen when taking SLIT involve local allergic reactions that tend to occur pretty rapidly, which occur after the first and second dose. However, they don’t tend to happen later on in the course of the treatment at nearly as high of a frequency,” Casale said.

These adverse events include oral pruritus, throat irritation, ear pruritus, mouth edema, oral paraesthesia, tongue pruritus, and lip swelling.

“But most of these events tend to be very mild, and some are moderate and very few tend to be severe,” he said. “Good comparator trials are lacking but for most of the data, the effectiveness of SLIT is very similar to SCIT.”

The effective dose has not been established for most US licensed extract, Linda Cox, MD, FAAAI, AAAAI president and solo practitioner in Ft. Lauderdale, Florida, said during the presentation.

“Costs may be a significant for multi-allergic patients,” Cox said. – By Samantha Costa

For more information:

Durham SR. #2611: SLIT: Implementation in your practice. Presented at the American Academy of Allergy, Asthma & Immunology annual meeting; Feb. 28-March 4, 2014; San Diego.

Disclosure: Casale reports financial ties with Teva, Novartis, Genentech, Boehringer Ingelheim, Circassia, Parexel, NIH, Cytos and Allrequest, and other organizational conflicts. Cox reports multiple committee and organizational disclosures. She also reports financial ties with Circassia, Medimmune, Merck and Stallergenes. Durham reports financial ties with Merck and Stallergenes.