Influence of Concomitant Opioids on Difelikefalin Treatment Outcomes in Adults with Moderate-to-Severe Pruritus on Maintenance Hemodialysis: Exploratory Analyses.

Burton JO, Grewal S, Schaufler T, Ruessmann D, Lowe M, Wen W, Fishbane S

Kidney & blood pressure research17 Dec 2025

PMID41406043PMCIDPMC12803522DOI10.1159/000549648PepBankPUB-41406043

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Summary

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Text rights: CC BY-NC. Results still quote short attributed sentences.

Results from this study6

6 results from studies that gave the peptide. 6 results from people.

01HumanNon-randomized trialEfficacy outcome
In hemodialysis patients, difelikefalin increased estimated attainment of at least 3-point itch reductions versus placebo, irrespective of opioid use.
In plain wordsIn hemodialysis patients, difelikefalin increased meaningful itch improvement compared with placebo, with or without opioid use.
Peptide
Difelikefalin
Outcome
IncreaseAt least 3-point WI-NRS reduction
Study
n: not reported in source
Comparator
Placebo
Analysis
Exploratory
Outcome group
Pruritus · Skin and wound
Studied dose
0.5 µg/kg · 12 weeksAs given in this study (human).
Source sentences
Summary
Regardless of opioid use, a greater estimated percentage of those receiving DFK achieved ≥3- or ≥4-point clinically relevant reductions in itch intensity (WI-NRS; p < 0.05), or complete response (≥80% weekly mean WI-NRS scores of 0 or 1) by week 12, versus PBO.
2 context sentences(design, population, supporting numbers)
Summary · context
Exploratory analyses were conducted from the phase 3, placebo (PBO)-controlled KALM-1 and KALM-2 trials (datasets pooled), and the phase 3, open-label, single-arm Study 3105.
Summary · context
Each trial assessed the safety and efficacy of DFK 0.5 µg/kg in adults with moderate-to-severe CKD-aP.
Report a problemFND-4140604301
02HumanNon-randomized trialEfficacy outcome
In hemodialysis patients, difelikefalin increased estimated attainment of at least 4-point itch reductions versus placebo, irrespective of opioid use.
In plain wordsIn hemodialysis patients, difelikefalin increased larger itch improvements compared with placebo, with or without opioid use.
Peptide
Difelikefalin
Outcome
IncreaseAt least 4-point WI-NRS reduction
Study
n: not reported in source
Comparator
Placebo
Analysis
Exploratory
Outcome group
Pruritus · Skin and wound
Studied dose
0.5 µg/kg · 12 weeksAs given in this study (human).
Source sentences
Summary
Regardless of opioid use, a greater estimated percentage of those receiving DFK achieved ≥3- or ≥4-point clinically relevant reductions in itch intensity (WI-NRS; p < 0.05), or complete response (≥80% weekly mean WI-NRS scores of 0 or 1) by week 12, versus PBO.
2 context sentences(design, population, supporting numbers)
Summary · context
Exploratory analyses were conducted from the phase 3, placebo (PBO)-controlled KALM-1 and KALM-2 trials (datasets pooled), and the phase 3, open-label, single-arm Study 3105.
Summary · context
Each trial assessed the safety and efficacy of DFK 0.5 µg/kg in adults with moderate-to-severe CKD-aP.
Report a problemFND-4140604302
03HumanNon-randomized trialEfficacy outcome
In hemodialysis patients, estimated complete itch response was greater with difelikefalin than placebo by week 12, irrespective of opioid use.
In plain wordsIn hemodialysis patients, complete itch response was greater with difelikefalin than placebo, with or without opioid use.
Peptide
Difelikefalin
Outcome
IncreaseComplete itch response
Study
n: not reported in source
Comparator
Placebo
Analysis
Exploratory
Outcome group
Pruritus · Skin and wound
Studied dose
0.5 µg/kg · 12 weeksAs given in this study (human).
Source sentences
Summary
Regardless of opioid use, a greater estimated percentage of those receiving DFK achieved ≥3- or ≥4-point clinically relevant reductions in itch intensity (WI-NRS; p < 0.05), or complete response (≥80% weekly mean WI-NRS scores of 0 or 1) by week 12, versus PBO.
2 context sentences(design, population, supporting numbers)
Summary · context
Exploratory analyses were conducted from the phase 3, placebo (PBO)-controlled KALM-1 and KALM-2 trials (datasets pooled), and the phase 3, open-label, single-arm Study 3105.
Summary · context
Each trial assessed the safety and efficacy of DFK 0.5 µg/kg in adults with moderate-to-severe CKD-aP.
Report a problemFND-4140604303
04HumanNon-randomized trialEfficacy outcome
In hemodialysis patients, difelikefalin improved itch-related quality of life more than placebo, irrespective of concomitant opioid use.
In plain wordsIn hemodialysis patients, difelikefalin improved itch-related quality of life more than placebo, with or without opioids.
Peptide
Difelikefalin
Outcome
Direction not reportedItch-related quality of life
Study
n: not reported in source
Comparator
Placebo
Analysis
Exploratory
Outcome group
Pruritus · Skin and wound
Studied dose
0.5 µg/kgAs given in this study (human).
Source sentences
Summary
Greater improvements in itch-related QoL were also reached with DFK, versus PBO, irrespective of concomitant opioid use.
2 context sentences(design, population, supporting numbers)
Summary · context
Exploratory analyses were conducted from the phase 3, placebo (PBO)-controlled KALM-1 and KALM-2 trials (datasets pooled), and the phase 3, open-label, single-arm Study 3105.
Summary · context
Each trial assessed the safety and efficacy of DFK 0.5 µg/kg in adults with moderate-to-severe CKD-aP.
Report a problemFND-4140604304
05HumanObservational studySafety outcome
Among difelikefalin recipients, nonfatal serious treatment-emergent adverse events occurred in 44.7% with concomitant opioids versus 19.0% without; the same pattern occurred with placebo (38.0% versus 15.9%).
In plain wordsAmong difelikefalin recipients, serious nonfatal adverse events were more common with opioid use than without, and the same pattern appeared with placebo.
Peptide
Difelikefalin
Outcome
IncreaseNonfatal serious treatment-emergent adverse events by opioid use
Study
n: not reported in source
Comparator
Difelikefalin recipients without concomitant opioids
Analysis
Exploratory
Outcome group
Adverse events · Whole body
Studied dose
0.5 µg/kgAs given in this study (human).
Measurements
Nonfatal serious TEAEs
44.7%
DFK+O
Nonfatal serious TEAEs
19%
DFK-O
Nonfatal serious TEAEs
38%
PBO+O
Nonfatal serious TEAEs
15.9%
PBO-O
Source sentences
Summary
With either treatment, nonfatal serious TEAEs were more common among concomitant opioid users (DFK+O: 44.7% vs. DFK-O: 19.0%; PBO+O: 38.0% vs. PBO-O: 15.9%), as were severe TEAEs.
2 context sentences(design, population, supporting numbers)
Summary · context
Exploratory analyses were conducted from the phase 3, placebo (PBO)-controlled KALM-1 and KALM-2 trials (datasets pooled), and the phase 3, open-label, single-arm Study 3105.
Summary · context
Each trial assessed the safety and efficacy of DFK 0.5 µg/kg in adults with moderate-to-severe CKD-aP.
Report a problemFND-4140604305
06HumanObservational studySafety outcome
Among difelikefalin recipients, severe treatment-emergent adverse events were more common with concomitant opioids than without opioids.
In plain wordsAmong difelikefalin recipients, opioid use was linked to more severe adverse events than no opioid use.
Peptide
Difelikefalin
Outcome
IncreaseSevere treatment-emergent adverse events by opioid use
Study
n: not reported in source
Comparator
Difelikefalin recipients without concomitant opioids
Analysis
Exploratory
Outcome group
Adverse events · Whole body
Studied dose
0.5 µg/kgAs given in this study (human).
Source sentences
Summary
With either treatment, nonfatal serious TEAEs were more common among concomitant opioid users (DFK+O: 44.7% vs. DFK-O: 19.0%; PBO+O: 38.0% vs. PBO-O: 15.9%), as were severe TEAEs.
2 context sentences(design, population, supporting numbers)
Summary · context
Exploratory analyses were conducted from the phase 3, placebo (PBO)-controlled KALM-1 and KALM-2 trials (datasets pooled), and the phase 3, open-label, single-arm Study 3105.
Summary · context
Each trial assessed the safety and efficacy of DFK 0.5 µg/kg in adults with moderate-to-severe CKD-aP.
Report a problemFND-4140604306

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
28 Oct 2026, 02:03 UTC
Study results updated
Version 1
27 Oct 2026, 16:35 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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Influence of Concomitant Opioids on Difelikefalin Treatment Outcomes in Adults with Moderate-to-Severe Pruritus on Maintenance Hemodialysis: Exploratory Analyses.

Summary

Results from this study6

Version history

Subjects

Publication types

MeSH terms

Keywords