{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T16:32:43Z","timestamp":1787157163578,"version":"build-2736575974"},"reference-count":48,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T00:00:00Z","timestamp":1766534400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T00:00:00Z","timestamp":1766534400000},"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":["Allergy"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tablet formulations of allergen extracts are widely recommended over other formulations for the sublingual immunotherapy (SLIT) of respiratory allergies. However, with adequate clinical trial evidence, SLIT (liquid) drop formulations may be a relevant allergy treatment option.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The RHAPSODY multinational, Phase III, parallel\u2010group, double\u2010blind, placebo\u2010controlled, randomised clinical study of adults with moderate\u2010to\u2010severe, grass\u2010pollen\u2010induced allergic rhinoconjunctivitis (ARC) with or without asthma was conducted at 45 investigating centres in six European countries. Participants received 26\u2009months of continuous treatment with active 5\u2010grass\u2010pollen SLIT drops or placebo. The primary efficacy endpoint was the average daily total combined score (TCS, comprising a symptom score and a rescue medication score) during the second peak grass pollen season (PGPS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of the 445 randomised patients (mean\u2009\u00b1\u2009standard deviation (range) age: 32.6\u2009\u00b1\u20099.9 (18\u201363); males: 55.1%), 389 completed the trial. The primary efficacy endpoint showed a statistically significant difference in favour of active treatment versus placebo (average difference in the daily TCS: 1.88 (95% CI: 0.60\u20133.17); relative difference 26.51% (95% CI: 9.42\u201340.55);\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0036). The difference (0.17 points) in the average weekly Rhinitis Quality of Life Questionnaire score during the second PGPS in favour of the active treatment was clinically relevant but not statistically significant. The differences in efficacy were generally driven by the medication score, rather than the symptom score. Most adverse events were mild and local.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>RHAPSODY was the first well\u2010powered clinical trial to show the positive risk\u2013benefit ratio of 5\u2010grass\u2010pollen SLIT drops in adult participants with moderate\u2010to\u2010severe grass\u2010pollen\u2010induced ARC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.70191","type":"journal-article","created":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T04:20:07Z","timestamp":1766636407000},"page":"2123-2132","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Five\u2010Grass\u2010Pollen Sublingual Immunotherapy Drops Are Efficacious and Well Tolerated in Adults: The\n                    <scp>RHAPSODY<\/scp>\n                    Phase\n                    <scp>III<\/scp>\n                    Trial"],"prefix":"10.1111","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6230-9706","authenticated-orcid":false,"given":"Alain","family":"Didier","sequence":"first","affiliation":[{"name":"Service de Pneumologie Allergologie and R\u00e9seau CRISALIS\/F\u2010CRIN INSERM, H\u00f4pital Larrey, CHU de Toulouse  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruta Gronskyte","family":"Juhl","sequence":"additional","affiliation":[{"name":"ALK\u2010Abell\u03cc A\/S  H\u00f8rsholm Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terrie","family":"Dalgaard","sequence":"additional","affiliation":[{"name":"ALK\u2010Abell\u03cc A\/S  H\u00f8rsholm Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Chartier","sequence":"additional","affiliation":[{"name":"ALK France  Paris la d\u00e9fense France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Devillier","sequence":"additional","affiliation":[{"name":"Department of Airway Diseases Universit\u00e9 de Versailles Saint\u2010Quentin, H\u00f4pital Foch  Suresnes France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,24]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.iac.2015.12.002"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.2500\/aap.2012.33.3603"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2007.03.034"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/clt2.12130"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.04.00013904"},{"issue":"3","key":"e_1_2_11_7_1","first-page":"168","article-title":"Allergy, Living and Learning: Diagnosis and Treatment of Allergic Respiratory Diseases in Europe","volume":"22","author":"Chivato T.","year":"2012","journal-title":"Journal of Investigational Allergology & Clinical Immunology"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/039463201202500137"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1185\/03007995.2011.559580"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2008.01666.x"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.04.061"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.10.035"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199908123410702"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2016.10.015"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.13213"},{"key":"e_1_2_11_16_1","unstructured":"GINA \u201cGlobal Strategy for Asthma Management and Prevention \u201d(2024) https:\/\/ginasthma.org\/2024\u2010report\/."},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.07.053"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2019.06.049"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.03.050"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2024.04.034"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2021.05.020"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.2500\/aap.2021.42.200109"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alit.2018.03.008"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reval.2023.103734"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2009.02063.x"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reval.2023.103734"},{"key":"e_1_2_11_27_1","unstructured":"National Assembly \u201cFrench governmental decree 2004\u2013188 \u201d(2004)."},{"key":"e_1_2_11_28_1","unstructured":"Haute Autorit\u00e9 de Sant\u00e9 \u201cCommission de la Transparence \u201d(2017)."},{"key":"e_1_2_11_29_1","volume-title":"Guideline on the Clinical Development of Products for Specific Immunotherapy for the Treatment of Allergic Diseases","year":"2008"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2022.01.004"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2019.01.024"},{"key":"e_1_2_11_32_1","unstructured":"LARGE Study \u201cLongitudinal Non\u2010Interventional Observational Study on Adherence Safety and Tolerability of AVANZ in Adults and GRAZAX and SLIToneULTRA in Adults and Children (5\u201317\u2009Years) in Patients With Allergic Rhinoconjunctivitis in Germany \u201d(2019) https:\/\/www.pei.de\/SharedDocs\/Downloads\/DE\/awb\/nis\u20100201\u20100300\/0235\u2010abschlussb.pdf?__blob=publicationFile&v=4."},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1081-1206(10)60571-6"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.2147\/JAA.S107830"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reval.2013.02.007"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.1991.tb00807.x"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.3111\/13696990701478856"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3109\/07853890109002087"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15207"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.01.049"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1472-9733.2008.00125.x"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.16252"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2006.01312.x"},{"issue":"8","key":"e_1_2_11_44_1","first-page":"1123","article-title":"First\u2010Line Treatment of Seasonal (Ragweed) Rhinoconjunctivitis. A Randomized Management Trial Comparing a Nasal Steroid Spray and a Nonsedating Antihistamine","volume":"156","author":"Juniper E. F.","year":"1997","journal-title":"CMAJ"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-6749(96)70135-5"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2024.01.038"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.12383"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.12187"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.2500\/aap.2024.45.240020"}],"container-title":["Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/all.70191","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/all.70191","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/all.70191","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T16:22:04Z","timestamp":1787156524000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/all.70191"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,24]]},"references-count":48,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1111\/all.70191"],"URL":"https:\/\/doi.org\/10.1111\/all.70191","archive":["Portico"],"relation":{},"ISSN":["0105-4538","1398-9995"],"issn-type":[{"value":"0105-4538","type":"print"},{"value":"1398-9995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,24]]},"assertion":[{"value":"2025-07-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}