Safety and tolerability of an SQ-standardized GRAss ALlergy immunotherapy tablet (GRAZAX®) in a real-life setting for three consecutive seasons - the GRAAL trial.

BACKGROUND AND OBJECTIVES: GRAZAX(®) (Phleum Pratense, 75,000 SQ-T/2,800 BAU, ALK, Denmark), an SQ-standardized grass allergy sublingual immunotherapy tablet for the desensitization of grass pollen-induced rhinoconjunctivitis, has been developed to facilitate patient access to specific immunotherapy (SIT), while minimizing the risk of serious treatment-related adverse events. As a minimum duration of 3 years is recommended for SIT treatment, the GRAAL trial aimed to assess the safety profile of GRAZAX(®) in real-world conditions during long-term treatment of patients with grass pollen-induced allergic rhinoconjunctivitis (ARC). METHODS: A multicentre, prospective, open-label, observational trial was conducted over three consecutive grass pollen seasons from November 2007 to October 2010 in France. A total of 130 physicians included 628 patients with previously documented ARC. Patients received one tablet daily (no up-titration) for at least 4 months before the expected start of the pollen season (pre-season), which was then maintained throughout the entire season (co-season). The primary endpoint was safety and tolerability (immediate, i.e. each year at first tablet administration, and long-term) after pre- and co-seasonal exposure to GRAZAX(®). RESULTS: Patients were treated for an average of 5.5 months per year. After administration of the first tablet, immediate tolerable reactions (defined as benign, local, of short duration [<30 minutes] and not requiring any symptomatic treatment) were experienced by 54.6%, 38.4% and 33.6% of the patients during the first, second and third years of treatment, respectively. Immediate intolerable reactions (required study discontinuation, symptomatic medication or lasted >30 minutes) occurred in 14 patients (2.2%) during GRAZAX(®) initiation, and one patient (0.3%) at treatment reintroduction during the second year. Adverse events considered to be related to GRAZAX(®) were reported by 46.2%, 14.4% and 1.8% of patients, during the first, second and third years of treatment, respectively. The most frequently reported adverse events were mild-to-moderate local events (at the oral and pharyngeal mucosa levels). These symptoms mainly occurred within the first month of treatment initiation and subsequent tablet reintroduction. CONCLUSION: Daily administration of GRAZAX(®) for three consecutive years was generally safe and well tolerated. An improvement in the incidence of adverse events related to treatment was observed at reintroduction of GRAZAX(®) and during the course of treatment. TRIAL REGISTRATION: http://clinicaltrials.gov (NCT01433510).