Effect of Roflumilast Cream (ARQ-151) on Itch and Itch-Related Sleep Loss in Adults with Chronic Plaque Psoriasis: Patient-Reported Itch Outcomes of a Phase 2b Trial

Abstract

Background Itch is the most bothersome symptom reported by patients with psoriasis. Safe and effective treatments for psoriasis that also address itch are needed. Objectives To report effects of roflumilast cream on itch-related outcomes from a Phase 2b trial. Methods Adults with chronic plaque psoriasis were randomized to roflumilast 0.3%, roflumilast 0.15%, or vehicle once-daily for 12 weeks. Psoriasis severity was assessed via the Investigator Global Assessment (IGA; a 5-point scale assessing plaque thickening, scaling, and erythema ranging from 0 [clear] to 4 [severe]) and ≥ 2 on a modified Psoriasis Area and Severity Index (PASI-HD, which combines severity of lesions and area affected, ranging from 0 [no disease] to 72 [maximal disease], with the actual percentage of the anatomical area involved in those patients with < 10% of anatomical area involved [e.g., 0.1 for 1% to 0.9 for 9%]). Itch was evaluated via Worst Itch Numeric Rating Scale (WI-NRS), Psoriasis Symptom Diary (PSD) Items 1 (severity of itch) and 2 (bother of itch), and itch-related sleep loss NRS scores. Post hoc correlation analyses between WI-NRS and PASI, WI-NRS and itch-related sleep loss, and WI-NRS and DLQI were also performed. Results Roflumilast-treated patients had significantly greater improvements than vehicle-treated patients in WI-NRS and PSD Items 1 and 2 beginning at Week 2 and in itch-related sleep loss Weeks 6 through 12. Among patients with baseline WI-NRS ≥ 6, significantly more patients achieved ≥ 4-point improvement with roflumilast than with vehicle as early as Week 2. Itch severity had low correlation with PASI while WI-NRS and IGA were not always aligned. Limitations The first assessment was at 2 weeks, limiting the ability to assess early onset of itch response. Conclusion Roflumilast cream improved itch and itch-related sleep loss associated with chronic plaque psoriasis. ClinicalTrials.gov identifier NCT03638258.

An update on topical therapies for psoriasis

“…Post hoc analysis of the phase 2b study found significant improvements in itch (as measured by the worst itch numeric rating scale, WI-NRS) and in itch-related sleep loss, with WI-NRS improvement occurring as early as week 2 in the roflumilast groups, and improvement in itch-related sleep loss from week 6 onward in both roflumilast groups [32 ▪ ].…”

“…Post hoc analysis of the phase 2b study found significant improvements in itch (as measured by the worst itch numeric rating scale, WI-NRS) and in itchrelated sleep loss, with WI-NRS improvement occurring as early as week 2 in the roflumilast groups, and improvement in itch-related sleep loss from week 6 onward in both roflumilast groups [32 ]. The DERMIS-1 and DERMIS-2 phase 3 trials each randomized participants over 2 years old with plaque psoriasis affecting from 2 to 20% BSA to receive roflumilast 0.3% or placebo in a 2 : 1 ratio.…”

Roflumilast 0.3% Cream: a Phosphodiesterase 4 Inhibitor for the Treatment of Chronic Plaque Psoriasis

“…39 Analyzing the effects of roflumilast cream on itchrelated outcomes on patients from the same trial, the authors found that roflumilast cream improved itch and itch-related sleep loss associated with chronic plaque psoriasis compared with vehicle, at 2 weeks of treatment. 41 A post hoc analyses of the same study data on 160 (48% of 331 patients randomized to roflumilast 0.3%, roflumilast 0.15%, or vehicle) with psoriasis involving the face and/or intertriginous areas found that the rates of adverse events were low in all treatment groups, similar to the overall population. Based on the author statements in a Research letter published in British Journal of Dermatology, 42 their results suggest that patients with plaque psoriasis on the face and/or intertriginous regions, which is frequently challenging to treat due to the sensitivity of these regions, may benefit from topical roflumilast 0.3%.…”

Novel Topical Treatments for Itch

“…Roflumilast cream was FDA approved for plaque psoriasis in July 2022, as it rapidly and effectively reduced itch severity, providing improvement after 2 weeks with a reduction in worst itch of − 4 on a 10-point scale at week 8 [ 16 , 17 ]. Furthermore, in two pivotal phase III trials, DERMIS-1 and DERMIS-2, 67.5% and 69.4% of patients treated with roflumilast and with baseline WI-NRS scores ≥ 4 had at least a 4-point reduction in score (WI-NRS Success) compared to 26.8% and 35.6% of patients treated with vehicle cream, respectively [ 18 ].…”