French experience: safety profile of SQ-standardised grass allergyimmunotherapy tablet in medical practice for 3 consecutive seasons– the GRAAL studyA Magnan 1 , G Magnier 2 , B Alexandre 2 , A Chartier 2 , J-P Meunier 3 , F Wessel 41Chest Medicine Department, Institut du Thorax, Nantes, France; 2 Medical Department, <strong>ALK</strong>, Courbevoie, France; 3 Clinical Department, Axonal CRO, Nanterre,France; 4 Private allergologist, Nantes, FranceGrass AITBackgroundThe aim of this study was to assess grass allergy immunotherapytablet (AIT) safety in patients with hay fever over 3consecutive grass pollen seasons (GPSs) in real life settings.MethodThe GRAAL study was initiated from Nov 2007 to Oct 2008and continued for 2 consecutive seasons (Jan to Oct in 2009and 2010) to assess the safety and tolerability profile ofgrass AIT (Grazax ® , Phleum pratense, 75,000 SQ-T/2,800BAU, <strong>ALK</strong>, Denmark). Each year, visits were performed2 to 4 months before the GPS (1st tablet intake or reintroductionperformed systematically under the physician’ssupervision) and at the end of the GPS.ResultThe initial cohort included 628 patients, of whom 72% werepolysensitised and 32% had asthma, selected from 130different sites. The mean exposure was 5.5 +/- 1.6 months/year.Adverse events (AEs) Season 2008 (S1) Season 2009 (S2) Season 2010 (S3)N=628 α N=367 N=277Patients with at least 1 AE related to grass AIT 290 (46.2%) 53 (14.4%) 5 (1.8%)[42.3%; 50.1%] β [10.8%; 18.0%] [0.2%; 3.4%]Subgroup of polysensitised patients with at least 1 related AE 217/451 (48.1%) 40/254 (15.7%) 4/188 (2.1%)[43.5%; 52.7%] [11.3%; 20.2%] [0.1%; 4.2%]Subgroup of asthmatic patients with at least 1 related AE 98/200 (49.0%) 26/125 (20.8%) 2/88 (2.3%)[42.1%; 55.9%] [13.7%; 27.9%] [0.0%; 5.4%]Patients with 1 tolerable reaction* at first administration 343 (54.6%) 141 (38.4%) 93 (33.6%)[50.7%; 58.5%] [33.4%; 43.4%] [28.0%; 39.1%]Patients with 1 adverse reaction** at first administration 14 (2.2%) 1 (0.3%) 0 (0.0%)[1.1%; 3.4%] [0.0%; 0.8%] [0.0%; 0.0%]Patients withdrawn for AEs 70 (11.1%) 7 (1.9%) 1 (0.4%)[8.7%; 13.6%] [0.5%; 3.3%] [0.0%; 1.1%]* Tolerable reaction: benign and local with low intensity lasting less than 30 min. not requiring any treatment** Adverse reaction: other than defined by ‘tolerable reaction’αN = number of patientsβ[] confidence interval 95%Over the 3 consecutive seasons, 4 patients (3 during season 1, and 1 during season 2) experienced 5 non-life threatening SAEs related to grass AIT.The per protocol analysis subgroup of 277 patients was included in all 3 consecutives seasons (mean exposure: 5.8 +/- 1.2 months/year).Adverse events (AEs) Season 2008 (S1) Season 2009 (S2) Season 2010 (S3) Comparison between the 3 seasons εN = 277 α N = 277 N = 277 Odds ratio (OR) P valuePatients with at least 1 AE related 107 (38.6%) 31 (11.2%) 5 (1.8%) OR (S2 vs. S1) = 0.20 P < 0.001to grass AIT [32.9%; 44.4%] β [7.5%; 14.9%] [0.2%; 3.4%] [0.14; 0.30] OR (S3 vs. S1) = 0.03 [0.01; 0.07]Patients with 1 tolerable reaction* 151 (54.5%) 108 (39.0%) 93 (33.6%) OR (S2 vs. S1) = 0.50 P < 0.001at first administration [48.6%; 60.4%] [33.2%; 44.7%] [28.0%; 39.1%] [0.39; 0.65] OR (S3 vs. S1) = 0.39 [0.30; 0.51] γPatients with 1 adverse reaction** 5 (1.8%) 1 (0.4%) 0 (0.0%)at first administration [0.2%; 3.4%] [0.0%; 1.1%] [0.0%; 0.0%]* Tolerable reaction: benign and local with low intensity lasting less than 30 min. not requiring any treatment** Adverse reaction: other than defined by ‘tolerable reaction’αN = number of patientsβ[ ] confidence interval 95%εγRepeated measures logistic regressionOdds ratio calculated on all patients with 1 tolerable or adverse reactionat first administrationFor this subgroup, the observed AEs during the study for 49.5% of thepatients were mainly local reactions (pruritus and oropharyngeal irritation,mouth oedema) which occurred during the 1st week of treatment, mainly atthe 1st intake. From one season to another, the rate of local moderate tosevere AEs decreased significantly (-38.4% in season 2, -25.6% in season 3).No generalised anaphylactic reaction occurred.ConclusionAdministration of SQ-standardised grass AIT for 3consecutive seasons, with an average annual exposureof 5.8 months, showed a significant yearly improvement(p
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