Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
The Patient - Patient-Centered Outcomes Research
Published in: The Patient - Patient-Centered Outcomes Research 2/2024

Open Access 09-01-2024 | Pruritus | Original Research Article

Impact of Difelikefalin on the Health-Related Quality of Life of Haemodialysis Patients with Moderate-To-Severe Chronic Kidney Disease-Associated Pruritus: A Single-Arm Intervention Trial

Authors: James Fotheringham, Julian Guest, Joerg Latus, Edgar Lerma, Isabelle Morin, Thilo Schaufler, Marco Soro, Sonja Ständer, Steven Zeig

Published in: The Patient - Patient-Centered Outcomes Research | Issue 2/2024

Login to get access

Abstract

Objective

Chronic kidney disease-associated pruritus (CKD-aP) can have a substantial negative impact on health-related quality of life (HRQoL), including an increased risk of depression, anxiety and sleep disturbance. This trial aimed to assess the impact of intravenous difelikefalin on HRQoL in haemodialysis patients with moderate-to-severe CKD-aP.

Methods

Post hoc analysis of an open-label, multicentre, single-arm intervention trial assessed pruritus severity and HRQoL at baseline and at 12 weeks of difelikefalin treatment using Worst Itching Intensity Numerical Rating Scale (WI–NRS), Sleep Quality Numeric Rating Scale (SQ–NRS), 5-D itch scale, Skindex-10 scale, EQ-5D-5L with Pruritus Bolt-On (EQ-PSO).

Results

A total of 222 patients received ≥ 1 dose of difelikefalin, and 197 patients completed 12 weeks of difelikefalin treatment. Clinically meaningful changes from baseline to 12 weeks were observed in all disease-specific measures: 73.7% of patients achieved a ≥ 3-point reduction in the weekly mean of 24 h WI–NRS scores and 66% of patients experienced ≥ 3-point improvements in SQ–NRS scores. Improvements were also observed in all Skindex-10 scale and 5-D itch scale domain scores. The percentage of patients reporting no problems in all EQ-PSO domains increased from 1.4 to 24.7% (p < 0.001), respectively. Patients’ generic HRQoL EQ-5D-5L mean utility and EQ-5D visual analogue scale scores increased from baseline to 12 weeks: mean changes 0.04 (p = 0.001) and 2.8 (p = 0.046), respectively.

Conclusions

Patients undergoing haemodialysis with moderate-to-severe CKD-aP receiving difelikefalin reported experiencing clinically meaningful improvements in both their pruritus symptoms and itch-related QoL.
ClinicalTrials.gov registration number, NCT03998163; first submitted, 7 May 2019.
Appendix
Available only for authorised users
Literature
1.
Nair D, Finkelstein FO. Pruritus as a patient-reported primary trial end point in hemodialysis: evaluation and implications. Am J Kidney Dis. 2020;76:148–51.CrossRefPubMed
2.
Shirazian S, Aina O, Park Y, Chowdhury N, Leger K, Hou L, Miyawaki N, Mathur VS. Chronic kidney disease-associated pruritus: impact on quality of life and current management challenges. Int J Nephrol Renovasc Dis. 2017;10:11–26.CrossRefPubMedPubMedCentral
3.
Swarna SS, Aziz K, Zubair T, Qadir N, Khan M. Pruritus associated with chronic kidney disease: a comprehensive literature review. Cureus. 2019;11: e5256.PubMedPubMedCentral
4.
Plewig N, Ofenloch R, Mettang T, Weisshaar E. The course of chronic itch in hemodialysis patients: results of a 4-year follow-up study of GEHIS (German Epidemiological Hemodialysis Itch Study). J Eur Acad Dermatol Venereol. 2019;33:1429–35.CrossRefPubMed
5.
Rayner HC, Larkina M, Wang M, Graham-Brown M, van der Veer SN, Ecder T, Hasegawa T, Kleophas W, Bieber BA, Tentori F, Robinson BM, Pisoni RL. International comparisons of prevalence, awareness, and treatment of pruritus in people on hemodialysis. Clin J Am Soc Nephrol. 2017;12:2000–7.CrossRefPubMedPubMedCentral
6.
Sukul N, Karaboyas A, Csomor PA, Schaufler T, Wen W, Menzaghi F, Rayner HC, Hasegawa T, Al Salmi I, Al-Ghamdi SMG, Guebre-Egziabher F, Urena-Torres PA, Pisoni RL. Self-reported pruritus and clinical, dialysis-related, and patient-reported outcomes in hemodialysis patients. Kidney Med. 2020;3(42–53): e1.
7.
Pisoni RL, Wikström B, Elder SJ, Akizawa T, Asano Y, Keen ML, Saran R, Mendelssohn DC, Young EW, Port FK. Pruritus in haemodialysis patients: international results from the Dialysis Outcomes and Practice Patterns Study (DOPPS). Nephrol Dial Transpl. 2006;21:3495–505.CrossRef
8.
Simonsen E, Komenda P, Lerner B, Askin N, Bohm C, Shaw J, Tangri N, Rigatto C. Treatment of uremic pruritus: a systematic review. Am J Kidney Dis. 2017;70:638–55.CrossRefPubMed
9.
Gardell LR, Spencer RH, Chalmers DT, Menzaghi F. Preclinical profile of CR845: a novel, long-acting peripheral kappa opioid receptor agonist. Poster Presentation at the International Association for the Study of Pain. 2008.
10.
Menzaghi F, Spencer R, Abrouk N, Lewis M, Chalmers D. (422) CR845, a peripheral kappa opioid, provides better pain relief with less nausea and vomiting than placebo in patients after bunionectomy. J Pain. 2015;16:S81.CrossRef
11.
12.
Burton J, Topf J, Fishbane S, Weiner D. Unmet medical needs in chronic-kidney-disease-associated pruritus. EMJ Nephrol. 2021;9:2–11.
13.
Fishbane S, Jamal A, Munera C, Wen W, Menzaghi F, Kalm Trial Investigators. A phase 3 trial of difelikefalin in hemodialysis patients with pruritus. N Engl J Med. 2020;382:222–32.
14.
Fishbane S, Mathur V, Germain MJ, Shirazian S, Bhaduri S, Munera C, Spencer RH, Menzaghi F, Trial Investigators. Randomized controlled trial of difelikefalin for chronic pruritus in hemodialysis patients. Kidney Int Rep. 2020;5:600–10.
15.
Topf J, Wooldridge T, McCafferty K, Schömig M, Csiky B, Zwiech R, Wen W, Bhaduri S, Munera C, Lin R, Jebara A, Cirulli J, Menzaghi F. Efficacy of difelikefalin for the treatment of moderate to severe pruritus in hemodialysis patients: pooled analysis of KALM-1 and KALM-2 phase 3 studies. Kidney Med. 2022;4: 100512.CrossRefPubMedPubMedCentral
16.
17.
Weiner DE, Vervloet MG, Walpen S, Schaufler T, Munera C, Menzaghi F, Wen W, Bhaduri S, Germain MJ, Trial Investigators. Safety and effectiveness of difelikefalin in patients with moderate-to-severe pruritus undergoing hemodialysis: an open-label, multicenter study. Kidney Med. 2022;4:100542.
18.
Naegeli AN, Flood E, Tucker J, Devlen J, Edson-Heredia E. The Worst Itch Numeric Rating Scale for patients with moderate to severe plaque psoriasis or psoriatic arthritis. Int J Dermatol. 2015;54:715–22.CrossRefPubMed
19.
Ashby D, Borman N, Burton J, Corbett R, Davenport A, Farrington K, Flowers K, Fotheringham J, Andrea Fox RN, Franklin G, Gardiner C, Martin Gerrish RN, Greenwood S, Hothi D, Khares A, Koufaki P, Levy J, Lindley E, Macdonald J, Mafrici B, Mooney A, Tattersall J, Tyerman K, Villar E, Wilkie M. Renal association clinical practice guideline on haemodialysis. BMC Nephrol. 2019;20:379.CrossRefPubMedPubMedCentral
20.
21.
Elman S, Hynan LS, Gabriel V, Mayo MJ. The 5-D itch scale: a new measure of pruritus. Br J Dermatol. 2010;162:587–93.CrossRefPubMed
22.
Mathur VS, Lindberg J, Germain M, Block G, Tumlin J, Smith M, Grewal M, McGuire D, Itch National Registry Investigators. A longitudinal study of uremic pruritus in hemodialysis patients. Clin J Am Soc Nephrol. 2010;5:1410–19.
23.
24.
Swinburn P, Lloyd A, Boye KS, Edson-Heredia E, Bowman L, Janssen B. Development of a disease-specific version of the EQ-5D-5L for use in patients suffering from psoriasis: lessons learned from a feasibility study in the UK. Value Health. 2013;16:1156–62.CrossRefPubMed
25.
Kimata N, Fuller DS, Saito A, Akizawa T, Fukuhara S, Pisoni RL, Robinson BM, Akiba T. Pruritus in hemodialysis patients: results from the Japanese Dialysis Outcomes and Practice Patterns Study (JDOPPS). Hemodial Int. 2014;18:657–67.CrossRefPubMed
26.
Ramakrishnan K, Bond TC, Claxton A, Sood VC, Kootsikas M, Agnese W, Sibbel S. Clinical characteristics and outcomes of end-stage renal disease patients with self-reported pruritus symptoms. Int J Nephrol Renovasc Dis. 2013;7:1–12.PubMedPubMedCentral
27.
Weiner D, Budden J, Woods S, Krishnarajah S, Morin I, Menzaghi I, Wen W, Bhaduri S. CKD-associated pruritus after 12 weeks of therapy with difelikefalin among hemodialysis patients with severe pruritus: a post hoc analysis of phase 3 studies. Am J Kidney Dis. 2022;79:S124.CrossRef
28.
Weiner D, Vervloet M, Menzaghi F, Warren W, Walpen S, Schaufler T, Morin I, Germain M. Improvement of itch with difelikefalin in CKD patients on dialysis by baseline itch severity. J Am Soc Nephrol. 2022;33:684 (Abstract SA-PO286).
29.
Cooper JT, Lloyd A, Sanchez JJG, Sörstadius E, Briggs A, McFarlane P. Health related quality of life utility weights for economic evaluation through different stages of chronic kidney disease: a systematic literature review. Health Qual Life Outcomes. 2020;18:310.CrossRefPubMedPubMedCentral
30.
Balieva F, Kupfer J, Lien L, Gieler U, Finlay AY, Tomas-Aragones L, Poot F, Misery L, Sampogna F, van Middendorp H, Halvorsen JA, Szepietowski JC, Lvov A, Marron SE, Salek MS, Dalgard FJ. The burden of common skin diseases assessed with the EQ5D: a European multicentre study in 13 countries. Br J Dermatol. 2017;176:1170–8.CrossRefPubMed
31.
Szende A, Janssen B, Cabases J. Self-Reported Population Health: An International Perspective based on EQ-5D. 2014: Spinger Open.
32.
Evangelidis N, Tong A, Manns B, Hemmelgarn B, Wheeler DC, Tugwell P, Crowe S, Harris T, Van Biesen W, Winkelmayer WC, Sautenet B, O’Donoghue D, Tam-Tham H, Youssouf S, Mandayam S, Ju A, Hawley C, Pollock C, Harris DC, Johnson DW, Rifkin DE, Tentori F, Agar J, Polkinghorne KR, Gallagher M, Kerr PG, McDonald SP, Howard K, Howell M, Craig JC. Developing a set of core outcomes for trials in hemodialysis: an international Delphi survey. Am J Kidney Dis. 2017;70:464–75.CrossRefPubMed
33.
Smyth B, van den Broek-Best O, Hong D, Howard K, Rogers K, Zuo L, Gray NA, de Zoysa JR, Chan CT, Lin H, Zhang L, Xu J, Cass A, Gallagher M, Perkovic V, Jardine M. Varying Association of extended hours dialysis with quality of life. Clin J Am Soc Nephrol. 2019;14:1751–62.CrossRefPubMedPubMedCentral
34.
Poku E, Harnan S, Rooney G, James MM, Hernandez-Alava M, Schaufler T, Thokala P, Fotheringham J. The relationship between chronic kidney disease-associated pruritus and health-related quality of life: a systematic review. Clin Kidney J. 2022;15:484–99.CrossRefPubMed
35.
Barbieri JS, Gelfand JM. Responsiveness of the EuroQol 5-Dimension 3-Level instrument, Dermatology Life Quality Index (DLQI) and DLQI-relevant for patients with psoriasis in the USA. Br J Dermatol. 2019;181:1088–90.
36.
37.
Chassang S, Snowberg E, Seymour B, Bowles C. Accounting for behavior in treatment effects: new applications for blind trials. PLoS ONE. 2015;10: e0127227.CrossRefPubMedPubMedCentral
38.
Nordon C, Karcher H, Groenwold RH, Ankarfeldt MZ, Pichler F, Chevrou-Severac H, Rossignol M, Abbe A, Abenhaim L, GetReal Consortium. The "efficacy-effectiveness gap": historical background and current conceptualization. Value Health. 2016;19:75–81.
39.
Kraft L, Schanz M, Schricker S, Ketteler M, Mayer G, Rostoker G, Manenti L, Schwenger V, Latus J. The first real-world experience of IV difelikefalin to treat chronic kidney disease-associated pruritus in haemodialysis patients. J Eur Acad Dermatol Venereol. 2023.
40.
World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310:2191–4.CrossRef
41.
Kumagai H, Ebata T, Takamori K, Muramatsu T, Nakamoto H, Suzuki H. Effect of a novel kappa-receptor agonist, nalfurafine hydrochloride, on severe itch in 337 haemodialysis patients: a phase III, randomized, double-blind, placebo-controlled study. Nephrol Dial Transpl. 2010;25:1251–7.CrossRef
42.
Stander S, Augustin M, Reich A, Blome C, Ebata T, Phan NQ, Szepietowski JC, International Forum for the Study of Itch Special Interest Group Scoring Itch in Clinical T. Pruritus assessment in clinical trials: consensus recommendations from the International Forum for the Study of Itch (IFSI) Special Interest Group Scoring Itch in Clinical Trials. Acta Derm Venereol. 2013;93:509–14.
43.
Vernon M, Stander S, Munera C, Spencer RH, Menzaghi F. Clinically meaningful change in itch intensity scores: an evaluation in patients with chronic kidney disease-associated pruritus. J Am Acad Dermatol. 2021;84:1132–4.CrossRefPubMed
44.
Puelles J, Fofana F, Rodriguez D, Silverberg JI, Wollenberg A, Dias Barbosa C, Vernon M, Chavda R, Gabriel S, Piketty C. Psychometric validation and responder definition of the sleep disturbance numerical rating scale in moderate-to-severe atopic dermatitis. Br J Dermatol. 2022;186:285–94.CrossRefPubMed
45.
Stander S, Fofana F, Dias-Barbosa C, Rodriguez D, Budhiarso I, Jabbar-Lopez ZK, Piketty C, Vernon M, Puelles J. The sleep disturbance numerical rating scale: content validity, psychometric validation, and meaningful within-patient change in prurigo nodularis. Dermatol Ther (Heidelb). 2023;13:1587–602.CrossRefPubMedPubMedCentral
Metadata
Title
Impact of Difelikefalin on the Health-Related Quality of Life of Haemodialysis Patients with Moderate-To-Severe Chronic Kidney Disease-Associated Pruritus: A Single-Arm Intervention Trial
Authors
James Fotheringham
Julian Guest
Joerg Latus
Edgar Lerma
Isabelle Morin
Thilo Schaufler
Marco Soro
Sonja Ständer
Steven Zeig
Publication date
09-01-2024
Publisher
Springer International Publishing
Published in
The Patient - Patient-Centered Outcomes Research / Issue 2/2024
Print ISSN: 1178-1653
Electronic ISSN: 1178-1661
DOI
https://doi.org/10.1007/s40271-023-00668-1

Other articles of this Issue 2/2024

The Patient - Patient-Centered Outcomes Research 2/2024 Go to the issue

Original Research Article

Preferences of Patients with Amyotrophic Lateral Sclerosis for Intrathecal Drug Delivery: Choosing between an Implanted Drug-Delivery Device and Therapeutic Lumbar Puncture

Practical Application

Pretesting Discrete-Choice Experiments: A Guide for Researchers

Original Research Article

A Best–Worst Scaling Study of the General Population's Preferences for Activities in Living Arrangements for Persons With Dementia

Original Research Article

Research Priorities to Increase Confidence in and Acceptance of Health Preference Research: What Questions Should be Prioritized Now?

Original Research Article

Prosocial Behaviour and Antibiotic Resistance: Evidence from a Discrete Choice Experiment

Original Research Article

Exploring the Preferences of Parents of Children with Myopia in Rural China for Eye Care Services Under Privatization Policy: Evidence from a Discrete Choice Experiment
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits