Clinically meaningful change in itch intensity scores: An evaluation in patients with chronic kidney disease–associated pruritus

To the Editor: Clinical trials to assess antipruritic effect of a treatment commonly use numerical rating scale (NRS) ranging from 0 (no itching) 10 (worst imaginable evaluate worst itch intensity. However, for drug be clinically relevant, magnitude reduction in NRS scores must represent meaningful improvement patients. Clinically changes with respect have been characterized dermatologic conditions,1Reich A. Riepe C. Anastasiadou Z. et al.Itch assessment visual analogue and scale: determination minimal important difference chronic itch.Acta Derm Venereol. 2016; 96: 978-980Crossref PubMed Scopus (44) Google Scholar, 2Mamolo C.M. Bushmakin A.G. Cappelleri J.C. Application Itch Severity Score patients moderate-to-severe plaque psoriasis: responder analyses.J Dermatolog Treat. 2015; 26: 121-123Crossref (21) 3Ständer S. Luger T.A. al.Validation severity item as measurement tool pruritus results phase 3 tofacitinib program.Acta 2018; 98: 340-345Crossref (12) 4Yosipovitch G. Reaney M. Mastey V. al.Peak Pruritus Numerical Rating Scale: psychometric validation definition assessing atopic dermatitis.Br J Dermatol. 2019; 181: 761-769Crossref (69) Scholar but our knowledge, threshold such among systemic kidney disease–associated (CKD-aP) has not established. address this knowledge gap, we conducted secondary analysis data pooled across groups 2, multicenter, double-blind, randomized, placebo-controlled study (NCT02858726) determine change required intensity on Worst Itching Intensity-NRS (WI-NRS) (Supplemental Fig 1; available via Mendeley at https://doi.org/10.17632/yjntdkbp9r.1) hemodialysis moderate severe pruritus. The was approved by Quorum Review Institutional Board before commencement accordance principles Good Practice, described International Council Harmonisation Guideline E6 general ethical outlined Declaration Helsinki. Patients provided written, informed consent any study-related assessments were performed. This demonstrated effects selective ?-opioid receptor agonist, difelikefalin, significant an itch-related quality life (QoL) over placebo.5Fishbane Mathur Germain al.Randomized controlled trial difelikefalin patients.Kidney Int Rep. 2020; 5: 600-610Abstract Full Text PDF (15) QoL collected 8-week period.5Fishbane Patient Global Impression Change (PGI-C), 7 categories “very much improved” worse,” (PGI-S), values (none) 4 (very severe), Skindex-10 5-D questionnaires selected anchor variables present Figs 2-5). WI-NRS estimated using anchor- distribution-based methods consistent United States Food Drug Administration guidance, Table I Supplemental I.Table IThresholds Intensity Scale primary anchor-based methods?Anchor-based linked patients' reports perception week 8 priori most closely relate concept measured WI-NRS. PGI-C variable because it is used change, including within populations pruritus, recommended Administration. “Minimally improved,” “minimally “much larger improvements. these anchors justified absence therapies (CKD-aP). Secondary included (1) 1-point least categorical PGI-S, which corresponded shift category (eg, moderate). clinical significance single-category shifts CKD-aP reinforced indicating that greater higher mortality; (2) direction degree questions asking whether itching got better or worse 1 (completely resolved) 5 (getting worse) past 2 weeks rate their (not present) (unbearable), respectively; (3) how often bothered (never bothered) 6 (always week.CriteriaWI-NRS score (week ? baseline), meanChange baseline, mean, %Effect size (Cohen d)Primary minimally improved?2.26?33.561.29 improved?3.02?42.991.65 improved?3.41?47.811.83Secondary PGI-S improved point?2.49?37.101.40 point?3.45?49.611.75 Direction (Itch)A little better?1.94?26.371.19A better?3.32?49.611.80 Degree (Itch Intensity)Improved point?3.02?45.231.82 (item 1) Bothersome points?2.65?39.051.47Mean (secondary anchors)?2.81?41.16PGI-C, Change; Severity.? Anchor-based week. Open table new tab PGI-C, Severity. 174 patients, who predominantly male (60%) African American (59%), median age 59 years (range, 26-84 years) history 4.4 years. Distribution-based estimates, considered provide lower boundaries thresholds, ranged ?0.67 ?1.78 points relative baseline mean 6.8 Tables II). In analysis, ?2.26 ?3.41 large sizes d > 1.0) associated definitions PGI-C. supported multiple (Table I, 1). identified specifically asks about condition, taking into consideration patient expectation. These analyses ?3 marks appropriate defining CKD-aP. significantly impacts patient's QoL, poor prognosis, represents unmet need due lack options. evidence should facilitate development treatments could ultimately affect care practice.