Rhinitis, sinusitis, and upper airway diseaseSQ-standardized sublingual grass immunotherapy: Confirmation of disease modification 2 years after 3 years of treatment in a randomized trial
Section snippets
Clinical trial design
Details of the randomized, double-blind, placebo-controlled trial, conducted according to the Declaration of Helsinki,17 have been published previously11, 12, 14 (ClinicalTrials.gov number: NCT00227279). From original 1 year of treatment, the trial was extended to cover in total 3 years of active treatment and 2 years of follow-up to investigate long-term and sustained efficacy of grass AIT (extension implemented in April 2005). The ethics committees in each country approved the trial as well
Efficacy
At randomization, 634 participants were included in the trial (316 active, 318 placebo). Five hundred forty-six participants completed the first season of the trial. When the trial was extended to another 4 years, 195 participants chose not to enroll or were not offered enrolment because of closure of sites. Thus, 351 participants continued in the extension (189 active, 162 placebo). These participants were a representative subset of the population originally included in the trial (see Dahl
Discussion
This is the first full 5-year, double-blind, multinational, placebo-controlled trial showing sustained clinical efficacy and disease modification 2 years after completion of 3 years of treatment with grass AIT. The 2nd follow-up and final year of this trial showed a statistically significant and clinically relevant sustained efficacy of 25% (P = .004) on the rhinoconjunctivitis symptom score in the active group relative to placebo. This sustained efficacy was observed in the face of the lowest
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The trial was sponsored by ALK, Denmark. S.R.D. has received consultancy and lecture fees and grant support from ALK. A. Kapp has consultant arrangements with DPC; has received grant support from Novartis, Astellas, UCB, ALK, and DPC; and is on the speakers’ bureau for Novartis, Astellas, UCB, and ALK. J.G.R.d.M. has received a grant from ALK. S.R. has received grant support from the Swedish Asthma and Allergy Association. R.D. has been on advisory boards for Nycomed, Boehringer Ingelheim, Novartis, TEVA, Oxagen, and Vectura and has received grant support from GlaxoSmithKline, Boehringer Ingelheim, Novartis, AstraZeneca, ALK, Stallergenes, and Pfizer. G.K.S. has been on advisory boards and is on the speakers’ bureau for ALK and is advisor and speaker for Merck. P.A.W., J.S.A., B.T., and B.R. are employed by ALK.
Disclosure of potential conflict of interest: S. R. Durham has received honoraria for lectures and consulting from ALK, Denmark, and Merck; has received research support from ALK, Denmark; and is head of the Allergy Consortium Immune Tolerance Network/National Institute of Allergy and Infectious Disease. W. Emminger, J. G. R. de Monchy, and G. K. Scadding have received research support from ALK. A. Kapp has provided consultation services for ALK. S. Rak has received consultation fees from AllergoPharma, lecture honoraria from Stallergenes, and research support from AllergoPharma and Allergenes, and has provided consultation services/expert witness testimony on the topic of sublingual immunotherapy. P. A. Wurtzen is a shareholder in ALK and a member of the Lundbeck Foundation Board of Directors. B. Tholstrup is a shareholder in ALK. B. Riis is a shareholder in ALK Abelló. R. Dahl has received lecture fees or is on the advisory board for Boehringer-Ingelheim, AstraZeneca, ALK, Airsonett, MSD, Novartis, Vectura, Elevation, Roche, and Norpharma; has received research support from ALK, Stalleren, Pfizer, Boehringer Ingelheim, AstraZeneca, Novartis, Airsonett, and GlaxoSmithKline; is Chairman of the Danish Respiratory Society; is Vice-chair of the Global Alliance against Chronic Respiratory Diseases; and is past president of Interasma. The rest of the authors declare that they have no relevant conflicts of interest.
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SQ-T (standardized quality tablet units) and BAU (biological activity units) are quantitative measures of biological activity; ie, the potency of allergen extracts/vaccines. One grass AIT contains 75,000 SQ-T of timothy (Phleum pratense) grass pollen extract (measure of total biological potency using ALK in-house reference), equivalent to 2,800 BAU (measure of total biological potency, defined by the FDA).