{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T12:05:07Z","timestamp":1793793907980,"version":"4.6.1"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T00:00:00Z","timestamp":1706227200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>A3 adenosine receptor (A3AR) is overexpressed in the skin and peripheral blood mononuclear cells of psoriasis patients. We investigated the efficacy\/safety of piclidenoson (CF101), an orally bioavailable A3AR agonist that inhibits IL\u201017 and IL\u201023 production in keratinocytes, in moderate\u2010to\u2010severe plaque psoriasis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The randomized, placebo\u2010 and active\u2010controlled, double\u2010blind phase 3 COMFORT\u20101 trial randomized patients (3:3:3:2) to piclidenoson 2\u2009mg BID, piclidenoson 3\u2009mg BID, apremilast 30\u2009mg BID or placebo. At Week 16, patients in the placebo arm were re\u2010randomized (1:1:1) to piclidenoson 2\u2009mg BID, piclidenoson 3\u2009mg BID or apremilast 30\u2009mg BID. The primary end point was the proportion of patients achieving \u226575% improvement in Psoriasis Area and Severity Index (PASI) from baseline (PASI\u201075) at Week 16 versus placebo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 529 patients were randomized and received \u22651 dose of study medication (safety population). The efficacy analysis population for the primary end point included 426 patients (piclidenoson 2\u2009mg BID, 127; piclidenoson 3\u2009mg BID, 103; apremilast, 118; placebo, 78). Piclidenoson at 2 and 3\u2009mg BID exhibited similar efficacy. The primary end point was met with the 3\u2009mg BID dose: PASI 75 rate of 9.7% versus 2.6% for piclidenoson versus placebo, <jats:italic>p<\/jats:italic>\u2009=\u20090.037. The PASI responses with piclidenoson continued to increase throughout the study period in a linear manner. At week 32, analysis in the per\u2010protocol population showed that a greater proportion of patients in the piclidenoson 3\u2009mg BID arm (51\/88, 58.0%) achieved improvement from baseline in Psoriasis Disability Index (PDI) compared to apremilast (59\/108, 55.1%), and the test for noninferiority trended towards significance (<jats:italic>p<\/jats:italic>\u2009=\u20090.072). The safety\/tolerability profile of piclidenoson was excellent and superior to apremilast.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Piclidenoson demonstrated efficacy responses that increased over time alongside a favourable safety profile. These findings support its continued clinical development as a psoriasis treatment (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link> identifier: NCT03168256).<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.19811","type":"journal-article","created":{"date-parts":[[2024,1,27]],"date-time":"2024-01-27T07:15:15Z","timestamp":1706339715000},"page":"1112-1120","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Efficacy and safety of piclidenoson in plaque psoriasis: Results from a randomized phase 3 clinical trial (<scp>COMFORT<\/scp>\u20101)"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9557-3642","authenticated-orcid":false,"given":"K. A.","family":"Papp","sequence":"first","affiliation":[{"name":"Probity Medical Research  Waterloo Ontario Canada"},{"name":"University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Beyska\u2010Rizova","sequence":"additional","affiliation":[{"name":"Multiprofile Hospital for Active Treatment  Pazardzhik Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. L.","family":"Gantcheva","sequence":"additional","affiliation":[{"name":"Diagnostic\u2010Consultative Centre  Sofia Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Slavcheva\u00a0Simeonova","sequence":"additional","affiliation":[{"name":"MHAT Rahila Angelova AD  Pernik Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Brezoev","sequence":"additional","affiliation":[{"name":"Diagnostic\u2010Consultative Aleksandrovska  Sofia Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Celic","sequence":"additional","affiliation":[{"name":"Clinical Centre of Republika Srpska  Banja Luka Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Groppa","sequence":"additional","affiliation":[{"name":"Spitalul Clinic Republican  Chisinau Moldova"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Blicharski","sequence":"additional","affiliation":[{"name":"Lubelskie Centrum Diagnostyczne  \u015awidnik Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Selmanagic","sequence":"additional","affiliation":[{"name":"Clinical Centre of Sarajevo University  Sarajevo Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Kalicka\u2010Dudzik","sequence":"additional","affiliation":[{"name":"Centrum Us\u0142ug Medycznych MaxMed  Bochnia Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. A.","family":"Calin","sequence":"additional","affiliation":[{"name":"SC PELICAN Impex SRL  Oradea Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Trailovic","sequence":"additional","affiliation":[{"name":"General Hospital Zajecar  Zajecar Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Ramon","sequence":"additional","affiliation":[{"name":"Rambam Medical Center  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Bareket\u2010Samish","sequence":"additional","affiliation":[{"name":"BioInsight Ltd  Binyamina Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z.","family":"Harpaz","sequence":"additional","affiliation":[{"name":"Can\u2010Fite BioPharma  Petah Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Farbstein","sequence":"additional","affiliation":[{"name":"Can\u2010Fite BioPharma  Petah Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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