Originally published by 2 Minute Medicine^® (view original article). Reused on AccessMedicine with permission.

1. In this randomized controlled trial, difelikefalin reduced pruritus intensity in patients with notalgia paresthetica over eight weeks of treatment as compared to placebo control.

2. Difelikefalin was also associated increased risk of adverse events compared to a placebo in notalgia paresthetica patients.

Evidence Rating Level: 1 (Excellent)

Study Rundown:

Notalgia paresthetica is a neuropathic pruritus disorder that is characterized by recurrent, localized itching in the interscapular and paravertebral regions. The condition is resistant to numerous treatments, decreasing patients’ quality of life due to discomfort. Difelikefalin is a selective kappa opioid receptor agonist. Notably, it has been previously demonstrated that activation of the kappa opioid receptor on peripheral sensory neurons suppresses itch sensations. However, there is a knowledge gap in understanding the efficacy and safety of oral difelikefalin for the treatment of moderate to severe pruritus associated with notalgia paresthetica. Overall, this study found that in patients with notalgia paresthetica, the reduction in itch intensity over an eight-week period was modestly greater with difelikefalin treatment than with a placebo. Though, the use of difelikefalin was associated with an increased risk of adverse events. This study was limited by having no pruritus-related quality of life scales that are validated in patients with notalgia paresthetica. Nevertheless, these findings are significant, as they demonstrate that oral difelikefalin can reduce pruritus intensity over an eight-week period in patients with notalgia paresthetica when compared to a placebo.

Click to read the study in NEJM

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In-Depth [randomized controlled trial]:

This randomized, double-blind, placebo-controlled trial was conducted at 28 sites in North America. Patients who were 18 to 80 years of age and who had a diagnosis of active notalgia paresthetica that was affirmed clinically by the site investigator, had dermatological findings (hyperpigmentation, hyperpigmentation, lichenification, or excoriation in the middle to upper back in the vicinity of the scapula), moderate-to-severe pruritus at baseline, had at least a six-month history of chronic pruritus caused by notalgia paresthetica, and were a candidate for systemic therapy were eligible for the study. Patients who did not meet these criteria were excluded from the study. The primary outcome measured was the change from baseline at week eight in the weekly mean of the daily 24-hour Worst Itching Intensity Numerical Rating Scale (WI-NRS) score. Outcomes in the primary analysis were assessed via efficacy analyses in an intention-to-treat population with linear regression models for repeated measures. Based on the primary analysis, the change from baseline in the weekly mean WI-NRS score at week eight was −4.0 points in the difelikefalin group and −2.4 points in the placebo group (difference in change, −1.6 points; 95% confidence interval, −2.6 to −0.6). Headache, dizziness, constipation, and increased urine output occurred more frequently in the difelikefalin group than in the placebo group. Overall, this study demonstrated that difelikefalin may reduce pruritus in patients with notalgia paresthetica over a period of eight weeks, though adverse events were associated with the novel treatment.

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