{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:59:39Z","timestamp":1781657979426,"version":"3.54.5"},"reference-count":19,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Renal Care"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Difelikefalin is well\u2010tolerated and reduces itch among adults undergoing haemodialysis (HD), with chronic kidney disease\u2010associated pruritus (CKD\u2010aP).<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aims to explore the influence of baseline itch severity on difelikefalin treatment outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Study 3105 (NCT03998163) was a 12\u2010week, phase 3, single\u2010arm, open\u2010label trial assessing safety and effectiveness of difelikefalin 0.5\u2009\u00b5g\/kg. We report key endpoints from 3105 by baseline itch severity, determined using the Worst Itching Intensity Numerical Rating Scale (WI\u2010NRS [moderate: WI\u2010NRS\u2009&lt;\u20097; severe: WI\u2010NRS\u2009\u2265\u20097]).<\/jats:p><\/jats:sec><jats:sec><jats:title>Participants<\/jats:title><jats:p>Adult participants undergoing maintenance HD (<jats:italic>n<\/jats:italic>\u2009=\u2009222) with mild\u2010to\u2010moderate CKD\u2010aP (WI\u2010NRS score\u2009\u2265\u20095 at baseline).<\/jats:p><\/jats:sec><jats:sec><jats:title>Measurements<\/jats:title><jats:p>The primary endpoint of 3105 was safety; secondary endpoints included reduction in itch intensity (WI\u2010NRS), and improvements in itch\u2010related quality of life (QoL; 5\u2010D itch scale) and sleep quality (Sleep Quality Numerical Rating Scale).<\/jats:p><\/jats:sec><jats:sec><jats:title>Findings<\/jats:title><jats:p>Mean (SD) age was 57.1 (13.3) years; mean (SD) baseline WI\u2010NRS scores were 6.0 (0.5) and 8.3 (0.9) for participants with moderate (<jats:italic>n<\/jats:italic>\u2009=\u200970\/222) or severe (<jats:italic>n<\/jats:italic>\u2009=\u2009152\/222) itch, respectively. No treatment\u2010related deaths occurred, and there were no safety concerns according to baseline itch severity. By week 12, both groups reported residual \u2018mild itch\u2019 according to mean (SD) WI\u2010NRS scores (moderate: 2.9 [2.2]; severe: 3.1 [2.3]). Approximately one in four participants demonstrated \u2018complete response\u2019 in itch reduction (moderate: 27.1%; severe: 25.0%). Clinically relevant improvements in itch\u2010related QoL and sleep quality occurred among both subgroups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Difelikefalin was well\u2010tolerated and effective in reducing itch in participants with moderate and severe baseline itch, supporting its broad use in a range of individuals on HD with CKD\u2010aP.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jorc.70017","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T15:50:11Z","timestamp":1746546611000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Influence of Baseline Itch Severity on Treatment Outcomes With Difelikefalin in Adults With Moderate\u2010to\u2010Severe Pruritus Receiving Maintenance Haemodialysis: An Exploratory Analysis"],"prefix":"10.1111","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0762-2270","authenticated-orcid":false,"given":"Kieran","family":"McCafferty","sequence":"first","affiliation":[{"name":"Barts Health NHS Trust London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thilo","family":"Schaufler","sequence":"additional","affiliation":[{"name":"CSL Vifor Glattbrugg Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8311-6214","authenticated-orcid":false,"given":"Pablo","family":"Molina","sequence":"additional","affiliation":[{"name":"Department of Nephrology FISABIO, Hospital Universitari Dr Peset Universitat de Val\u00e8ncia Val\u00e8ncia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murray","family":"Lowe","sequence":"additional","affiliation":[{"name":"CSL Vifor Glattbrugg Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren","family":"Wen","sequence":"additional","affiliation":[{"name":"Cara Therapeutics Stamford Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel E.","family":"Weiner","sequence":"additional","affiliation":[{"name":"William B. Schwartz, MD, Division of Nephrology Tufts Medical Center Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2009.09586.x"},{"key":"e_1_2_11_3_1","unstructured":"European Medicines Agency.2022.Kapruvia (Difelikefalin): An Overview of Kapruvia and Why It Is Authorised in the EU. Accessed October 2024.https:\/\/www.ema.europa.eu\/en\/documents\/overview\/kapruvia-epar-medicine-overview_en.pdf."},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1912770"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xkme.2022.100513"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ckj\/sfab142"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfp588"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/2054358120954024"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.00100110"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2024k64q3cs2"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.03280317"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000016812"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-1620"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/ckj\/sfae274"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xkme.2020.08.011"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xkme.2022.100512"},{"key":"e_1_2_11_17_1","unstructured":"US Food and Drug Administration (FDA).2021. KORSUVA (Difelikefalin): Highlights of Prescribing Information. Accessed October 2024.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2021\/214916s000lbl.pdf."},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2020.06.991"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfad245"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xkme.2022.100542"}],"container-title":["Journal of Renal Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jorc.70017","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T08:06:46Z","timestamp":1751011606000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jorc.70017"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,6]]},"references-count":19,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1111\/jorc.70017"],"URL":"https:\/\/doi.org\/10.1111\/jorc.70017","archive":["Portico"],"relation":{},"ISSN":["1755-6678","1755-6686"],"issn-type":[{"value":"1755-6678","type":"print"},{"value":"1755-6686","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,6]]},"assertion":[{"value":"2024-11-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70017"}}