{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "ClinCompetence Cologne GmbH, 50933 Cologne, Germany",
    "Institute of Medical Statistics and Computational Biology, Faculty of Medicine, University of Cologne, 50931 Cologne, Germany",
    "Inmunotek S.L., 28805 Alcalá de Henares, Madrid, Spain"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Esther Raskopf"
    },
    {
      "affs": [
        1
      ],
      "name": "Carmen Fierro Ballester"
    },
    {
      "affs": [
        0
      ],
      "name": "Hacer Sahin"
    },
    {
      "affs": [
        0
      ],
      "name": "Nadine Katzke"
    },
    {
      "affs": [
        0
      ],
      "name": "Christian Neuhof",
      "orcid": "0009-0004-9323-6887"
    },
    {
      "affs": [
        0
      ],
      "name": "Laura Day"
    },
    {
      "affs": [
        0
      ],
      "name": "Anna Rybachuk",
      "orcid": "0000-0001-5306-5412"
    },
    {
      "affs": [
        0
      ],
      "name": "Silke Allekotte"
    },
    {
      "affs": [
        2
      ],
      "name": "Miguel Casanovas",
      "orcid": "0000-0003-2330-3963"
    },
    {
      "affs": [
        2
      ],
      "name": "José Luis Subiza",
      "orcid": "0000-0002-0134-5321"
    },
    {
      "affs": [
        2
      ],
      "name": "Sandra del Pozo",
      "orcid": "0000-0001-5205-4105"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/217y5t3avfk6a.bib",
  "cited_by": 0,
  "doi": "10.3390/jcm15197637",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13666366/?tool=EBI",
  "id": "217y5t3avfk6a",
  "issns": [
    "2077-0383"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13666366",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2723|Allergic Rhinitis and Sensitization"
    ]
  ],
  "openalex": "W7196928453",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13666366/pdf/?tool=EBI",
  "pmcid": "PMC13666366",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/217y5t3avfk6a.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:31Z",
      "native_id": "PMC:PMC13666366",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13666366"
    },
    {
      "first_seen": "2026-10-30T12:20:00Z",
      "native_id": "10.3390/jcm15197637",
      "source": "crossref",
      "url": "https://www.mdpi.com/2077-0383/15/19/7637"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2723|Allergic Rhinitis and Sensitization",
      "subfield": "immunology"
    }
  ],
  "title": "Clinical Outcomes in Placebo-Injection and Injection-Free Cohorts in Birch Pollen Allergy: An Exploratory Cross-Study Comparison",
  "title_text": "Clinical Outcomes in Placebo-Injection and Injection-Free Cohorts in Birch Pollen Allergy: An Exploratory Cross-Study Comparison",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:00Z",
  "url": "https://research.draconitic.com/paper/217y5t3avfk6a",
  "venue": "Journal of clinical medicine",
  "versions": []
}