{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T04:42:17Z","timestamp":1791088937437,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,6,1]],"date-time":"2012-06-01T00:00:00Z","timestamp":1338508800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1"}],"funder":[{"name":"Cytos Biotechnology"},{"DOI":"10.13039\/100009946","name":"Allergopharma","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100009946","id-type":"DOI","asserted-by":"crossref"}]},{"name":"ALK-Albello"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2012,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Allergen\u2010specific immunotherapy (<jats:styled-content style=\"fixed-case\">SIT<\/jats:styled-content>) with native allergen extracts and allergoids has been performed successfully for decades. Preliminary studies revealed the use of recombinant allergen\u2010preparations as a promising option for <jats:styled-content style=\"fixed-case\">SIT<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The present study was designed to investigate the dose\u2010ranging safety in SCIT with a mixture of five recombinant grass pollen allergens containing equimolar amounts of r<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>hl p 1, r<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>hl p2, r<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>hl p 5a, r<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>hl p 5b and r<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>hl p 6, adsorbed to aluminium hydroxide.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A randomized, double blind, placebo\u2010controlled, dose\u2010ranging safety study (Eudra<jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content> number 2007\u2010002808\u201018) was performed in 50 patients with allergic rhinoconjunctivitis, with or without asthma. Patients were randomized to groups of 10 to receive maximum doses of 20, 40, 80 or 120\u00a0\u03bcg of total grass pollen recombinant protein or placebo.<\/jats:p><jats:p>The primary end\u2010point of this trial was the number of patients with at least one systemic reaction with possible, probable or definite relationship to the study medication determined at the end of the up\u2010dosing phase. Secondary end\u2010points included titrated intracutaneous test with natural six\u2010grass pollen extract, allergen\u2010specific conjunctival provocation test as well as IgG and IgE\u2010levels throughout the study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Eight of the 50 patients revealed systemic reactions grade 1 or 2 corresponding to the primary end\u2010point definition. No systemic reactions grade 3 or 4 occurred in any dosage group. The systemic reactions were well distributed among the active groups. Results of secondary end\u2010points imply that the study medication is effective and provokes immunological effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Clinical Relevance<\/jats:title><jats:p>The first <jats:styled-content style=\"fixed-case\">DBPC SCIT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">DRF<\/jats:styled-content> with a mixture of recombinant <jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>hleum allergens (<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>hl p 1, 2, 5a, 5b, 6) in patients with rhinoconjunctivitis plus\/minus asthma showed no major side effects in very high doses up to 120\u00a0\u03bcg.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1365-2222.2012.03971.x","type":"journal-article","created":{"date-parts":[[2012,1,31]],"date-time":"2012-01-31T16:27:22Z","timestamp":1328027242000},"page":"936-945","source":"Crossref","is-referenced-by-count":53,"title":["Specific subcutaneous immunotherapy with recombinant grass pollen allergens: first randomized dose\u2010ranging safety study"],"prefix":"10.1111","volume":"42","author":[{"given":"L.","family":"Klimek","sequence":"first","affiliation":[{"name":"Center for Rhinology and Allergology Wiesbaden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Schendzielorz","sequence":"additional","affiliation":[{"name":"Center for Rhinology and Allergology Wiesbaden Germany"},{"name":"Department of Otorhinolaryngology University Hospital of Ruprecht\u2010Karls University, Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Pinol","sequence":"additional","affiliation":[{"name":"Center for Rhinology and Allergology Wiesbaden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O.","family":"Pfaar","sequence":"additional","affiliation":[{"name":"Center for Rhinology and Allergology Wiesbaden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.04.00013904"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2001.118891"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-6749(98)70271-4"},{"key":"e_1_2_6_5_1","first-page":"CD001936","article-title":"Allergen injection immunotherapy for seasonal allergic rhinitis","author":"Calderon MA","year":"2007","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199908123410702"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1398-9995.2002.1o3264.x"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2002.121317"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2222.2001.01161.x"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2007.01.025"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.iac.2006.02.001"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2007.01609.x"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000069013"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-6749(98)70084-3"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2222.2000.00955.x"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.1991.tb01662.x"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1159\/000121468"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.2008.01938.x"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2005.06.004"},{"key":"e_1_2_6_20_1","unstructured":"European Medicines Agency (EMEA). Committee for Medicinal Products of Human Use (CHMP) and Efficacy Working Party (EWP): Guideline on the clinical development of products for specific immunotherapy for the treatment of allergic diseases. European Medicines Agency CHMP\/EWP\/18504\/2006.2008."},{"key":"e_1_2_6_21_1","first-page":"211","article-title":"Akkuttherpie anaphylakter Reaktionen. Ergebnis einer interdisziplin\u00e4ren Konsensuskonferenz","volume":"3","author":"Tryba M","year":"1994","journal-title":"Allergo J"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2003.08.009"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2007.01612.x"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/08923970701620008"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2006.01219_1.x"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2005.11.014"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2222.2000.00910.x"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1517\/14740330802457208"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2005.00790.x"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2005.09.054"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2008.01.072"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2007.01.022"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-6749(03)02022-0"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2004.1943.x"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.5.3252"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2222.2001.01145.x"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.1995.tb01170.x"}],"container-title":["Clinical &amp; Experimental Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2222.2012.03971.x","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2222.2012.03971.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2222.2012.03971.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T04:50:20Z","timestamp":1700542220000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2222.2012.03971.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,6]]},"references-count":36,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2012,6]]}},"alternative-id":["10.1111\/j.1365-2222.2012.03971.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2222.2012.03971.x","archive":["Portico"],"relation":{},"ISSN":["0954-7894","1365-2222"],"issn-type":[{"value":"0954-7894","type":"print"},{"value":"1365-2222","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,6]]}}}