Researchers who presented their findings at the American Academy of Allergy, Asthma and Immunology’s annual meeting in February shed new light on the benefits of using immunotherapy to treat allergic rhinitis.
David I. Bernstein, MD, professor of medicine and co-director of the Allergy Fellowship Training Program in the division of immunology, allergy and rheumatology at the University of Cincinnati College of Medicine in Ohio, said his research demonstrated that sublingual immunotherapy (SLIT) tablet therapy can be used effectively in patients who may be allergic to Timothy grass and short ragweed and who also have additional allergic sensitivities.
“The presence of sensitization to other aeroallergens in addition to those pollen allergies being treated does not apparently affect treatment response,” he said. Some participants had conjunctivitis, while others did not.
More than 80% of the patients participating in grass- or ragweed-sublingual tablet studies for treatment of seasonal allergic rhinitis were sensitized to other aeroallergens, including tree pollen and house dust mites. Sensitization was determined by measuring serum specific immunoglobulin E (IgE) to indoor and outdoor aeroallergens. “Studies of the ragweed and grass tablet demonstrated significant efficacy when compared to placebo, despite the very high frequency of participating patients with seasonal allergic rhinitis who were sensitized to multiple allergens other than the one they were treated for,” Dr. Bernstein said.
If clinically indicated, Dr. Bernstein said the new sublingual grass and ragweed tablets can be used with confidence in patients with the other unrelated allergies identified by skin testing or measuring serum specific IgE.
The bottom line is that patients with moderate to severe seasonal allergic rhinitis caused by grass pollen allergy or ragweed allergy who are not controlled adequately with medication can be of¬fered an alternative treatment in the form of sublingual tablet immunotherapy. This can be well suited for patients with severe allergies during the grass and ragweed pollen seasons. It is recommended that patients take tablets on a daily basis beginning 12 to 16 weeks prior to the start of the season and continue through the grass or ragweed seasons. “Patients may prefer this option over allergy injections, which are generally administered on a year-round basis,” Dr. Bernstein said.
Furthermore, Dr. Bernstein said that additional sublingual tablet products, such as medications for house dust mites, are currently under development. “This modality may be particularly attractive to children or individuals who are uncomfortable with receiving regular subcutaneous allergen injections,” he said.
Timothy Grass SLIT Tablets Show Promise
Research by Amarjot Kaur, PhD, executive director of biostatistics and research at Merck Research Laboratories in Kenilworth, N.J., revolved around a post hoc efficacy and safety study of Timothy grass SLIT tablets (Merck’s Grastek) and evaluated study participants with varying pre-treatment levels of specific Timothy grass IgEs.
Pre-treatment IgE levels against Timothy grass and its allergen components (Phl p) were determined using the diagnostic tool ImmunoCAP-ISAC for a sub-set of 1,140 randomized North American study participants in a double-blind, placebo-controlled Grastek clinical trial. The participants were Timothy grass skin prick test positive and IgE positive. The total symptom plus medication score over the entire pollen season and treatment-related adverse events was determined by pre-treatment Phl p-IgE levels.
“Results found subjects with detectable and higher pre-treatment Phl p-IgE trended toward higher efficacy and increased incidence of having at least one treatment-related adverse event,” Dr. Kaur said. These results indicate that pre-treatment levels of specific Phlp-IgE sensitization could continue to be explored to possibly further improve the patient benefit for allergen immunotherapy.
Further exploration may be necessary to identify optimal cutoff, she said. Future investigations will be needed to replicate these findings and also to examine the impact of more than one allergen component on efficacy and safety.
Epinephrine Use Evaluated in SLIT Tablets
Jennifer Maloney, MD, clinical director of respiratory and immunology, Merck Research Laboratories, Kenilworth, N.J., reported that her post hoc study evaluated the use of epinephrine among 8,804 participants in 16 clinical trials for three rapidly dissolving SLIT tablets, including Timothy grass (Merck’s Grastek), short-ragweed (Merck’s Ragwitek), and house dust mite (Merck’s MK-8237, an investi-gational product). Some participants had conjunctivitis, while others did not.
Epinephrine was used 13 times in grass SLIT tablet trials, eight of which were for SLIT tablet-related adverse events—four for systemic reactions and four for local events of pruritus and/or swelling in the mouth and/or throat. The remaining five administrations were unrelated to grass SLIT tablets. In ragweed trials, epinephrine was used nine times, four of which were SLIT tablet-related adverse events; in house dust mite trials, epinephrine was administered once for a SLIT tablet-related event.
Results found that for the 8,804 participants studied, epinephrine administrations were uncommon (event rate=0.1%), and 43% were for events that the investigator deemed unrelated to SLIT tablets, Dr. Maloney said.
“The data from my presentation indicates that epinephrine use is infrequent when treating side effects related to the Merck SLIT tablets,” Dr. Maloney added.
The Future of Treating Allergic Rhinitis with Immunotherapy
With the increased research in SLIT and the availability of sublingual tablets ap¬proved by the U.S. Food and Drug Administration, allergic rhinitis patients have gained more options in the method of immunotherapy methods. “SLIT is not for everyone, but having the option may increase the number of patients willing to undergo immunotherapy, especially those who cannot commit to the time requirements for regular injections in the office or for younger patients who have an aversion to needle sticks,” said Bryan D. Leatherman, MD, a specialist in sinus and allergy disorders as well as otolaryngology-head and neck surgery at Coastal Sinus and Allergy Center in Gulfport, Miss. “The safety profile of SLIT allows for home administration without as much risk of life-threatening anaphylactic reactions as home subcutaneous immunotherapy.”
Looking ahead, Dr. Leatherman believes that the use of SLIT as a preventive measure may also become more of the norm. “As more SLIT products become available, we may be able to start treating young children with allergic rhinitis, even those who are 2 or 3 years old, to help reduce the risk of subsequently developing asthma—a potentially life-threatening allergic disease,” he said.
Sandra Y. Lin, MD, associate professor in the department of otolaryngology-head and neck surgery at Johns Hopkins School of Medicine in Baltimore, believes that increasing the use of SLIT could broaden access to immunotherapy. “Patients are able to take SLIT at home, and young children tolerate it better than injections,” she said. “In addition, in medically underserved areas or rural areas, it may be difficult to have accessibility to injections.”
“With the greater understanding of how immunotherapy can prevent asthma and new sensitivities, we may be able to prevent these from happening in children that are highly atopic,” Dr. Lin added.
As the science of immunotherapy advances, new approaches to immune modulation will likely become avail¬able, said Matthew W. Ryan, MD, associate professor in the department of otolaryngology at the University of Texas Southwestern Medical Center in Dallas. For example, allergen molecules can be conjugated to other immunostimulatory molecules to augment the immunologic response to the vaccine. “Small studies using these conjugated allergen vaccines have shown that immunologic tolerance can be accomplished safely with a short course of treatment,” he said. “If additional studies support the efficacy and safety of these agents, it is possible that we will be able to treat patients with a course of subcutaneous injection immunotherapy that lasts months, rather than years.”
Karen Appold is a freelance medical writer based in Pennsylvania.