Efficacy and safety of oral nalbuphine extended release in prurigo nodularis: results of a phase 2 randomized controlled trial with an open-label extension phase.

BACKGROUND: Treatment of prurigo nodularis (PN) is challenging and new treatment options are needed. OBJECTIVE: To evaluate the efficacy and safety of two oral doses of the kappa opioid agonist and mu opioid antagonist nalbuphine extended release (NAL-ER) tablets in a phase 2, multicentre, randomized, double-blind, placebo-controlled trial with an open-label, 50-week extension phase. METHODS: Subjects with moderate-to-severe PN were randomized to NAL-ER 81 mg (NAL-ER81) or 162 mg (NAL-ER162) tablets twice-daily or placebo for 8 weeks of stable dosing following a 2-week titration period. Subjects completing Week 10 with a Worst Itch Numerical Rating Scale (WI-NRS) score ≥5 at the time of rollover (or during the observation period) were eligible for open-label treatment. RESULTS: Of 63 randomized subjects, 62 were treated and comprised the modified intent-to-treat population (MITT), 50 completed 10 weeks of treatment. In the MITT analysis, 8 subjects (44.4%) treated with NAL-ER162 (P = 0.32) and 6 (27.3%) treated with NAL-ER81 (P = 0.78) achieved ≥30% reduction from baseline in 7-day WI-NRS at Week 10 (primary efficacy endpoint) vs. 8 (36.4%) in the placebo group. Itch reduction was significant among 8/12 (66.7%) subjects completing Week 10 treated with NAL-ER162 vs. placebo (8/20, 40.0%; P = 0.03). Additionally, 6 subjects (33.3%) treated with NAL-ER162 and 3 (13.6%) treated with NAL-ER81 achieved ≥50% reduction from baseline in 7-day WI-NRS at Week 10 (coprimary endpoint). Extended open-label treatment was associated with further improvements in itch reduction and favourable changes in PN lesion activity as assessed by Prurigo Activity Score. Adverse events occurred predominantly during dose titration and were of mild-to-moderate severity. The safety profile did not change with extended open-label treatment. CONCLUSION: In adult subjects with PN, oral treatment with NAL-ER 162 mg twice daily provided measurable anti-pruritic efficacy in subjects completing ≥10 weeks of treatment and was well tolerated (ClinicalTrials.gov: NCT02174419).

Prurigo Activity Score (PAS): validity and reliability of a new instrument to monitor chronic prurigo.

BACKGROUND: Currently available tools to monitor patients with chronic prurigo over time focus on pruritus and quality of life parameters, while no instrument objectively assessing the pruriginous lesions is yet available. OBJECTIVE: The objective of this study was to develop a physician-assessed Prurigo Activity Score (PAS), a new tool to monitor the distribution and activity of chronic prurigo lesions and to evaluate its reliability and validity. METHODS: The 7-item PAS questionnaire as well as validated pruritus intensity scales (VAS, NRS) and a skin-related quality of life score (DLQI) were completed for 264 patients (172 females, age 61 years) at least twice over a period of 2 years. In addition, a 60-min test-retest reliability test was performed by four experts for a random sample of 12 patients. RESULTS: The PAS showed good test-retest reliability (Cohens κ > 0.61; Cronbach-alpha > 0.76), ordinal or metric items showed high inter-rater reliability (Kendalls > 0.61) and items recording the number of lesions correlated significantly to each other (P < 0.001). The highest correlation to external constructs was achieved with DLQI. The feasibility test conducted by four raters indicated the suitability of PAS for tracking chronic prurigo in the clinical setting. DISCUSSION: The PAS is a useful tool to objectively monitor pruriginous lesions in chronic prurigo patients over time. The sensitivity of change in the PAS score should be analysed in future studies.

Influence of a mindfulness meditation-based stress reduction intervention on rates of skin clearing in patients with moderate to severe psoriasis undergoing phototherapy (UVB) and photochemotherapy (PUVA).

OBJECTIVE: This study tests the hypothesis that stress reduction methods based on mindfulness meditation can positively influence the rate at which psoriasis clears in patients undergoing phototherapy or photochemotherapy treatment. METHODS: Thirty-seven patients with psoriasis about to undergo ultraviolet phototherapy (UVB) or photochemotherapy (PUVA) were randomly assigned to one of two conditions: a mindfulness meditation-based stress reduction intervention guided by audiotaped instructions during light treatments, or a control condition consisting of the light treatments alone with no taped instructions. Psoriasis status was assessed in three ways: direct inspection by unblinded clinic nurses; direct inspection by physicians blinded to the patient's study condition (tape or no-tape); and blinded physician evaluation of photographs of psoriasis lesions. Four sequential indicators of skin status were monitored during the study: a First Response Point, a Turning Point, a Halfway Point, and a Clearing Point. RESULTS: Cox-proportional hazards regression analysis showed that subjects in the tape groups reached the Halfway Point (p = .013) and the Clearing Point (p = .033) significantly more rapidly than those in the no-tape condition, for both UVB and PUVA treatments. CONCLUSIONS: A brief mindfulness meditation-based stress reduction intervention delivered by audiotape during ultraviolet light therapy can increase the rate of resolution of psoriatic lesions in patients with psoriasis.

Review of pruritus therapy.

Treatment of pruritus is based on determining the etiology of the itch. The evaluation should include a detailed history, complete physical examination, and appropriate laboratory tests. There are many therapies available, and treatment should be tailored to the individual patient.