Clinical Outcomes in Placebo-Injection and Injection-Free Cohorts in Birch Pollen Allergy: An Exploratory Cross-Study Comparison
- 1ClinCompetence Cologne GmbH, 50933 Cologne, Germany
- 2Institute of Medical Statistics and Computational Biology, Faculty of Medicine, University of Cologne, 50931 Cologne, Germany
- 3Inmunotek S.L., 28805 Alcalá de Henares, Madrid, Spain
Abstract
Background/Objectives: Placebo responses can complicate the interpretation of allergen immunotherapy (AIT) trials because symptom- and medication-based outcomes may be influenced by the trial context in addition to treatment-specific effects. Injection-free comparison cohorts are rarely available in conventional double-blind, placebo-controlled AIT trials. We therefore conducted an exploratory post hoc cross-study comparison of clinical outcomes in two placebo-injection cohorts and an injection-free cohort of birch pollen-allergic participants. Methods: Data from three prospective clinical studies evaluating the mannan-conjugated birch pollen allergoid EP-088-T502—T502-SIT-020, T502-SIT-045, and T502-SIT-068—were assembled for this cross-study comparison. Placebo-injection cohorts from studies T502-SIT-020 and T502-SIT-045 were compared with the injection-free cohort from study T502-SIT-068. Clinical outcomes included the Combined Symptom and Medication Score (CSMS), daily Symptom Score (dSS), and daily Medication Score (dMS). Results: The primary peak-period analysis included 60, 93, and 160 participants from T502-SIT-020, T502-SIT-045, and T502-SIT-068, respectively. During the site-specific 14-day peak birch pollen periods, median CSMS was 2.14 in the injection-free cohort compared with 1.34 and 1.07 in the T502-SIT-020 and T502-SIT-045 placebo-injection cohorts, respectively. These values corresponded descriptively to approximately 37% and 50% lower cohort medians, respectively, relative to the injection-free cohort. Median dSS, which was defined consistently across the three source studies, was 1.22 in the injection-free cohort compared with 0.78 and 0.70 in the two placebo-injection cohorts. Median dMS was 0.93 compared with 0.39 and 0.36, respectively. The same between-cohort pattern was observed in the secondary fixed 1–30 April analysis. Conclusions: Both placebo-injection cohorts showed lower CSMS and dSS values than the injection-free cohort. Because the cohorts were non-concurrent and derived from separate studies, the observed differences do not establish a causal effect of placebo injections.
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BibTeX
@article{raskopf2026clinical,
title = {{Clinical Outcomes in Placebo-Injection and Injection-Free Cohorts in Birch Pollen Allergy: An Exploratory Cross-Study Comparison}},
author = {Esther Raskopf and Carmen Fierro Ballester and Hacer Sahin and Nadine Katzke and Christian Neuhof and Laura Day and Anna Rybachuk and Silke Allekotte and Miguel Casanovas and José Luis Subiza and Sandra del Pozo},
journal = {Journal of clinical medicine},
year = {2026},
month = oct,
doi = {10.3390/jcm15197637},
url = {https://europepmc.org/article/PMC/PMC13666366},
note = {CC BY},
}
RIS
TY - JOUR
TI - Clinical Outcomes in Placebo-Injection and Injection-Free Cohorts in Birch Pollen Allergy: An Exploratory Cross-Study Comparison
AU - Esther Raskopf
AU - Carmen Fierro Ballester
AU - Hacer Sahin
AU - Nadine Katzke
AU - Christian Neuhof
AU - Laura Day
AU - Anna Rybachuk
AU - Silke Allekotte
AU - Miguel Casanovas
AU - José Luis Subiza
AU - Sandra del Pozo
PY - 2026
DA - 2026/10/01
JO - Journal of clinical medicine
DO - 10.3390/jcm15197637
UR - https://europepmc.org/article/PMC/PMC13666366
AB - Background/Objectives: Placebo responses can complicate the interpretation of allergen immunotherapy (AIT) trials because symptom- and medication-based outcomes may be influenced by the trial context in addition to treatment-specific effects. Injection-free comparison cohorts are rarely available in conventional double-blind, placebo-controlled AIT trials. We therefore conducted an exploratory post hoc cross-study comparison of clinical outcomes in two placebo-injection cohorts and an injection-free cohort of birch pollen-allergic participants. Methods: Data from three prospective clinical studies evaluating the mannan-conjugated birch pollen allergoid EP-088-T502—T502-SIT-020, T502-SIT-045, and T502-SIT-068—were assembled for this cross-study comparison. Placebo-injection cohorts from studies T502-SIT-020 and T502-SIT-045 were compared with the injection-free cohort from study T502-SIT-068. Clinical outcomes included the Combined Symptom and Medication Score (CSMS), daily Symptom Score (dSS), and daily Medication Score (dMS). Results: The primary peak-period analysis included 60, 93, and 160 participants from T502-SIT-020, T502-SIT-045, and T502-SIT-068, respectively. During the site-specific 14-day peak birch pollen periods, median CSMS was 2.14 in the injection-free cohort compared with 1.34 and 1.07 in the T502-SIT-020 and T502-SIT-045 placebo-injection cohorts, respectively. These values corresponded descriptively to approximately 37% and 50% lower cohort medians, respectively, relative to the injection-free cohort. Median dSS, which was defined consistently across the three source studies, was 1.22 in the injection-free cohort compared with 0.78 and 0.70 in the two placebo-injection cohorts. Median dMS was 0.93 compared with 0.39 and 0.36, respectively. The same between-cohort pattern was observed in the secondary fixed 1–30 April analysis. Conclusions: Both placebo-injection cohorts showed lower CSMS and dSS values than the injection-free cohort. Because the cohorts were non-concurrent and derived from separate studies, the observed differences do not establish a causal effect of placebo injections.
SN - 2077-0383
ER -