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Randomized controlled trials define shape of dose response for Pollinex Quattro Birch allergoid immunotherapy.

ABSTRACT: BACKGROUND:The Birch Allergoid, Tyrosine Adsorbate, Monophosphoryl Lipid A (POLLINEX® Quattro Plus 1.0 ml Birch 100%) is an effective, well-tolerated short course subcutaneous immunotherapy. We performed 2 phase II studies to determine its optimal cumulative dose. METHODS:The studies were conducted in Germany, Austria and Poland (EudraCT numbers: 2012-004336-28 PQBirch203 and 2015-000984-15 PQBirch204) using a wide range of cumulative doses. In both studies, subjects were administered 6 therapy injections weekly outside the pollen season. Conjunctival Provocation Tests were performed at screening, baseline and 3-4 weeks after completing treatment, to quantify the reduction in Total Symptom Scores (as the primary endpoint) with each cumulative dose. Multiple Comparison Procedure and Modeling analysis was used to test for the dose response, shape of the curve and estimation of the median effective dose (ED50 ), a measure of potency. RESULTS:Statistically significant dose responses (P < .01 & .001) were seen, respectively. The highest cumulative dose in PQBirch204 (27 300 standardized units [SU]) approached a plateau. Potency of the PQBirch was demonstrated by an ED50 2723 SU, just over half the current dose. Prevalence of treatment-emergent adverse events was similar for active doses, most being short-lived and mild. Compliance was over 85% in all groups. CONCLUSION:Increasing the cumulative dose of PQBirch 5.5-fold from 5100 to 27 300 SU achieved an absolute point difference from placebo of 1.91, a relative difference 32.3% and an increase in efficacy of 50%, without compromising safety. The cumulative dose response was confirmed to be curvilinear in shape.

SUBMITTER: Worm M

PROVIDER: S-EPMC6175210 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Randomized controlled trials define shape of dose response for Pollinex Quattro Birch allergoid immunotherapy.

Worm M M Higenbottam T T Pfaar O O Mösges R R Aberer W W Gunawardena K K Wessiepe D D Lee D D Kramer M F MF Skinner M M Lees B B Zielen S S

Allergy 20180619 9

<h4>Background</h4>The Birch Allergoid, Tyrosine Adsorbate, Monophosphoryl Lipid A (POLLINEX<sup>®</sup> Quattro Plus 1.0 ml Birch 100%) is an effective, well-tolerated short course subcutaneous immunotherapy. We performed 2 phase II studies to determine its optimal cumulative dose.<h4>Methods</h4>The studies were conducted in Germany, Austria and Poland (EudraCT numbers: 2012-004336-28 PQBirch203 and 2015-000984-15 PQBirch204) using a wide range of cumulative doses. In both studies, subjects we ...[more]

PMID: 29779247

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Project description:BackgroundPrevious clinical trials with birch pollen subcutaneous immunotherapy have been conducted over a 1- to 2-year treatment period and involved mostly a single geographic location.ObjectiveThis study (EudraCT-Number: 2005-000025-35) intended to evaluate the effect of subcutaneous immunotherapy with high-dose hypoallergenic birch pollen allergoid in patients with confirmed moderate to severe seasonal allergic rhinitis/rhinoconjunctivitis over a 3-year course in 19 European centres.MethodsAdults with confirmed birch pollen allergy (n = 253) were randomized to preseasonal placebo (n = 129) or active treatment (n = 124). Primary endpoint was change in Symptom Medication Score after 2 years treatment (2007).ResultsThe change in Symptom Medication Score of active- vs placebo-treated patients for the Full Analysis Set (n = 227, 15.2% reduction, P = 0.0710) and Per-Protocol Set (n = 216, 16.7% reduction, P = 0.0523) showed a positive trend, although significance was not achieved. The primary endpoint, assessed in 2007, coincided with the lowest pollination during the study period. In a subgroup analysis of patients in the north-eastern region (n = 102), where birch is the major tree and consequently patients' exposure is higher, changes in Symptom Medication Score (32.7% reduction, P = 0.0034) and median number of well days (P = 0.0232) were highly significant in favour of the active group. During the open-label third year of treatment, the mean Symptom Medication Score of active-treated patients was further reduced despite an increased pollen count. Subcutaneous immunotherapy was well tolerated and consistent with the known safety profile.Conclusions and clinical relevanceAlthough the primary endpoint was not reached for the Full Analysis Set, a significant and clinically relevant effect on Symptom Medication Score was clearly demonstrated for the subgroup of patients in the north-eastern region of Europe, where birch is the predominant tree species. Proving efficacy of birch allergen subcutaneous immunotherapy is challenging due to the numerous factors influencing birch pollen allergen exposure in field studies.

Project description:Despite the clear health benefits of exercise, exercised-induced weight loss is often less than expected. The term 'exercise energy compensation' is used to define the amount of weight loss below what is expected for the amount of exercise energy expenditure. We examined the dose-response effects of exercise volume on energy compensation in postmenopausal women.Data from Alberta Physical Activity and Breast Cancer Prevention (ALPHA) and Breast Cancer and Exercise Trial in Alberta (BETA) were combined for the present analysis. The ALPHA and BETA trials were two-centred, two-armed, 12-month randomized controlled trials. The ALPHA trial included 160 participants randomized to 225 min per week of aerobic exercise, and the BETA trial randomized 200 participants to each 150 and 300 min per week of aerobic exercise. All participants were aged 50-74 years, moderately inactive (<90 min per week of exercise), had no previous cancer diagnosis and a body mass index between 22 and 40 kg m-2. Energy compensation was based on changes in body composition (dual-energy X-ray absorptiometry scan) and estimated exercise energy expenditure from completed exercise volume. Associations between Δenergy intake, ΔVO2peak and Δphysical activity time with energy compensation were assessed.No differences in energy compensation were noted between interventions. However, there were large inter-individual differences in energy compensation between participants; 9.4% experienced body composition changes that were greater than expected based on exercise energy expenditure, 64% experienced some degree of energy compensation and 26.6% experienced weight gain based on exercise energy expenditure. Increases in VO2peak were associated with reductions in energy compensation (β=-3.44 ml kg-1 min-1, 95% confidence interval for β=-4.71 to -2.17 ml kg-1 min-1; P=0.0001).Large inter-individual differences in energy compensation were noted, despite no differences between activity doses. In addition, increases in VO2peak were associated with lower energy compensation. Future studies are needed to identify behavioral and metabolic factors that may contribute to this large inter-individual variability in energy compensation.

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Randomized controlled trials define shape of dose response for Pollinex Quattro Birch allergoid immunotherapy.

Publications

Randomized controlled trials define shape of dose response for Pollinex Quattro Birch allergoid immunotherapy.

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