Timothy Grass Pollen Allergen Extract Sublingual Tablets (Grastek®)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco.
Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved a second pollen extract as immunotherapy to treat grass pollen-induced allergic rhinitis. The extract contains Timothy grass allergen extract formulated in sublingual tablets. Timothy grass is one of the most common grasses in the United States and has been shown to be cross-reactive with other grasses, including sweet vernal, orchard, perennial rye, Kentucky blue, meadow fescue, and redtop. The first approved product is a mixed pollen extract (Oralair) that contains sweet vernal, orchard, perennial rye, Timothy, and Kentucky bluegrass. Timothy grass pollen allergen extract is marketed by Merck as Grastek.
Timothy grass pollen allergen extract is indicated as immunotherapy for the treatment of grass pollen-induced allergic rhinitis with or without conjunctivitis confirmed by positive skin test or pollen-specific IgE antibodies for Timothy grass or cross-reactive grass pollens in patients aged 5-65 years.1
The recommended dose is one tablet (sublingually) daily starting at least 12 weeks before the expected onset of each grass pollen season and continued throughout the season.1 The extract may be taken daily for three consecutive years.1 Each tablet contains 2800 bioequivalent allergy units. The first dose should be given under the supervision of a physician and the patient should be observed for at least 30 minutes to monitor for possible severe systemic or local allergic reactions.
The tablets provide a more convenient alternative to allergy shots that are given by a health care provider. The Timothy allergen extract is approved for use in children as young as 5 years.
Sublingual administration may be less effective than subcutaneous injection.2,3,4,5 The allergen extract can cause systemic allergic reactions (anaphylaxis) or severe local reactions (laryngopharyngeal swelling).1 An epinephrine auto-injection should be prescribed to patients receiving this extract. Patients taking medication that may counteract the effect of epinephrine (e.g., beta-blockers, alpha-adrenergic blockers) should not be prescribed the allergen extract. The extract is contraindicated in patients with severe and uncontrolled asthma, any severe systemic reaction, or a history of eosinophilic esophagitis. Common adverse events (vs placebo) in adults are oral pruritus (27% vs 3.5%), throat irritation (23% vs 3%), ear pruritus (13% vs 1%), and mouth edema (11% vs 1%). Throat irritation and oral pruritus were most common in pediatric patients. In clinical trials, 4.9% of adults discontinued treatment due to treatment-related adverse events compared to 0.9% on placebo. The most common adverse events were oral pruritus, mouth edema, and swollen tongue.6
The efficacy of the Timothy extract was supported by two short-term studies (approximately 24 weeks) and one 5-year grass pollen season study. The short-term studies were in patients ages 5-65 years and the long-term study was in adults ages 18-65 years. The extract was initiated approximately 12 weeks before the start of the grass pollen season. Subjects were randomized to the extract or placebo and were allowed to take symptom-relieving medications (antihistamines, topical, or systemic corticorticosteroids). Efficacy was based on self-reported rhinoconjunctivitis daily symptom scores (DSS) and daily medication scores (DMS), and the total combination scores (TCS). The FDA criteria of relevant efficacy is an average difference between placebo of -15% and the upper bound of the 95% confidence interval (CI) of -10%. This means an average reduction from placebo of 15% with a 95% CI of no worse than -10%. For the adult study (n = 1301), TCS difference between the extract and placebo was -23% (95% CI, -36% to -13%) and for the pediatric study (n = 307), -26% (95% CI, -38.2% to -10.1%). In the 5-year study, subjects received the extract or placebo for 3 years and were observed for 2 years post treatment. Efficacy results were -34% (95% CI, -42 to 26) for year 1, -41% (95% CI, -52 to -29) for year 2, -34% (95% CI, -45 to -21) for year 3, and -27% (95% CI, -40 to -12) for 1 year after stopping treatment. Efficacy was not sustained for the second year after stopping treatment.
This is the second recently approved allergen extract. The first, Oralair, is a mixed extract while Grastek is only Timothy grass extract. For Oralair, the grass reference is Timothy grass pollen and is cross sensitive to other grasses. Therefore, it is not clear whether the mixed extract offers any clear clinical advantages. These products provide an effective and more convenient form of immunotherapy for hay fever. The relative effectiveness of sublingual vs subcutaneous immunotherapy is not completely clear. Some studies suggest that sublingual is less effective than subcutaneous. The wholesale cost for Grastek is $247.50 for a 30-day supply, which is less expensive than Oralair ($300).
- Grastek Prescribing Information. Whitehouse Station, NJ: Merck; April 2014.
- Chelladurai Y, Lin SY. Effectiveness of subcutaneous versus sublingual immunotherapy for allergic rhinitis: Current update. Curr Opin Otolaryngol Head Neck Surg 2014;22:211-215.
- Aasbjerg K, et al. Immunological comparison of allergen immunotherapy tablet treatment and subcutaneous immunotherapy against grass allergy. Clin Exp Allergy 2014,44:417-428.
- Nelson HS. Subcutaneous immunotherapy versus sublingual immunotherapy: which is more effective?
J Allergy Clin Immunol Pract 2014;2:144-149.
- Chelladurai Y, et al. Effectiveness of subcutaneous versus sublingual immunotherapy for the treatment of allergic rhinoconjunctivitis and asthma: A systematic review. J Allergy Clin Immunol Pract 2013;1:361-369.
- http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/AllergenicProductsAdvisoryCommittee/UCM378092.pdf. Accessed May 13, 2014.