{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:46:07Z","timestamp":1785717967229,"version":"3.56.0"},"reference-count":47,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Mannan\u2010conjugated allergoids represent an effective option for treating allergic diseases. This study evaluated the clinical impact of the mannan\u2010conjugated, polymerised birch pollen allergoid EP\u2010088_T502 in patients with birch pollen\u2010induced allergic rhinoconjunctivitis over 3\u2009years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Following up to a double\u2010blind, placebo\u2010controlled dose\u2010finding study, in this open, long\u2010term extension study, 154 birch pollen\u2010allergic patients were enrolled in Germany. Patients were treated with a cumulative dose of 48,000 mTU EP\u2010088_T502 administered subcutaneously over five pre\u2010seasonal visits in each of the two treatment years (2021, 2022) with a subsequent follow\u2010up year in 2023. The primary efficacy endpoint was the combined symptom and medication score (CSMS) during the peak birch pollen season, which was compared with the CSMS of the placebo group during the peak pollen season of 2020. Safety, tolerability, and immunogenicity were also analysed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared to the placebo group of the preceding study, median CSMS during the peak birch pollen seasons showed reductions of 47.5% in 2021 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), 51.8% in 2022 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), and 36.5% in 2023 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Median daily symptom scores were reduced by 40.7% in 2021 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), 40.7% in 2022 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), and 25.6% in 2023 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.010). Median daily medication scores reached 0.07 in 2021 and 0.04 in 2022 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and were reduced by 65.9% in 2023 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.003). Immunological responses showed a 4.82\u2010fold increase in\n                      <jats:italic>Bet v1<\/jats:italic>\n                      sIgG4 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001) and a marked decrease (\u221265.5%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001) in the sIgE\/sIgG4 ratio after the first treatment phase. EP\u2010088_T502 demonstrated good safety and tolerability, with only six mild to moderate systemic allergic reactions (Grade I\/II). No epinephrine was used.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this open\u2010label study, two consecutive years of pre\u2010seasonal short\u2010course allergen immunotherapy (AIT) with EP\u2010088_T502 markedly reduced symptoms and medication need in patients with birch pollen\u2010induced rhinoconjunctivitis. Persistent therapeutic effects observed during the follow\u2010up year, although limited by attrition of the study population, suggest sustained clinical improvement and indicate the potential disease\u2010modifying impact of this treatment regimen.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cea.70323","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T07:47:01Z","timestamp":1777535221000},"page":"893-903","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sustained Clinical Improvement in Birch Pollen Allergy After Two Pre\u2010Seasonal Short Courses of Allergen\u2010Specific Immunotherapy: A Long\u2010Term Open\u2010Label Extension Study"],"prefix":"10.1111","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1928-810X","authenticated-orcid":false,"given":"Ralph","family":"M\u00f6sges","sequence":"first","affiliation":[{"name":"ClinCompetence Cologne GmbH  Cologne Germany"},{"name":"Institute of Medical Statistics and Computational Biology, Faculty of Medicine University of Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4110-0484","authenticated-orcid":false,"given":"Friederike","family":"H\u00fcffmeier","sequence":"additional","affiliation":[{"name":"Institute of Medical Statistics and Computational Biology, Faculty of Medicine University of Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2455-0192","authenticated-orcid":false,"given":"Ludger","family":"Klimek","sequence":"additional","affiliation":[{"name":"Center for Rhinology &amp; Allergology  Wiesbaden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4374-9639","authenticated-orcid":false,"given":"Oliver","family":"Pfaar","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Section of Rhinology and Allergy, University Hospital Marburg, Philipps\u2010Universit\u00e4t Marburg  Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9323-6887","authenticated-orcid":false,"given":"Christian","family":"Neuhof","sequence":"additional","affiliation":[{"name":"ClinCompetence Cologne GmbH  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5306-5412","authenticated-orcid":false,"given":"Anna","family":"Rybachuk","sequence":"additional","affiliation":[{"name":"ClinCompetence Cologne GmbH  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5699-4305","authenticated-orcid":false,"given":"Cengizhan","family":"Acikel","sequence":"additional","affiliation":[{"name":"ClinCompetence Cologne GmbH  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5516-2013","authenticated-orcid":false,"given":"Hacer","family":"Sahin","sequence":"additional","affiliation":[{"name":"ClinCompetence Cologne GmbH  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0222-5954","authenticated-orcid":false,"given":"Silke","family":"Allekotte","sequence":"additional","affiliation":[{"name":"ClinCompetence Cologne GmbH  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5205-4105","authenticated-orcid":false,"given":"Sandra","family":"del Pozo","sequence":"additional","affiliation":[{"name":"Inmunotek S.L.  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