Efficacy and safety of apremilast in pediatric patients with moderate-to-severe plaque psoriasis: 16-week results from SPROUT, a randomized controlled trial.

BACKGROUND: Approved systemic treatment options are limited for pediatric patients with moderate to severe plaque psoriasis. OBJECTIVE: To assess the efficacy and safety of apremilast over 16 weeks in pediatric patients with plaque psoriasis. METHODS: SPROUT (NCT03701763) was a phase 3, multicenter, randomized, double-blind, placebo-controlled study of apremilast in patients aged 6-17 years with moderate-to-severe psoriasis (Psoriasis Area and Severity Index [PASI] ≥12, body surface area ≥10%, static Physician Global Assessment [sPGA] ≥3) inadequately controlled by/inappropriate for topical therapy. Patients were stratified by age group and randomized (2:1) to apremilast (20 or 30 mg BID based on weight) or placebo for 16 weeks, followed by apremilast extension to 52 weeks. RESULTS: Of 245 patients randomized (apremilast: 163; placebo: 82), 221 (90%) completed the double-blind phase (apremilast: 149; placebo: 72). Significantly more patients achieved sPGA response and ≥75% reduction in PASI with apremilast than placebo, regardless of baseline age, weight, or disease severity. No new safety signals were observed. LIMITATIONS: Sample size of subgroup analyses. CONCLUSIONS: Improvements in global disease activity and skin involvement were significantly greater in pediatric patients treated with apremilast versus placebo. Adverse events were consistent with the known apremilast safety profile.

Efficacy and safety of apremilast in patients with moderate to severe plaque psoriasis of the scalp: Results of a phase 3b, multicenter, randomized, placebo-controlled, double-blind study.

BACKGROUND: Many patients with psoriasis are bothered by symptoms in highly visible, pruritic areas, such as the scalp. OBJECTIVE: To evaluate the efficacy and safety of apremilast for moderate to severe scalp psoriasis. METHODS: This phase 3b, double-blind, placebo-controlled study randomized adults with moderate to severe scalp psoriasis who had inadequate response/intolerance to at least 1 topical scalp psoriasis therapy (NCT03123471). The primary endpoint was the proportion of patients who achieved Scalp Physician Global Assessment response, defined as score of 0 (clear) or 1 (almost clear), with at least a 2-point reduction, at week 16. Secondary endpoints included at least a 4-point improvement from baseline in Whole Body Itch and Scalp Itch Numeric Rating Scales (NRSs) and mean improvement in Dermatology Life Quality Index (DLQI) at week 16. RESULTS: There were 303 randomized patients (placebo: n = 102; apremilast: n = 201). With apremilast, significantly more patients achieved Scalp Physician Global Assessment (43.3% vs 13.7%), Scalp Itch NRS (47.1% vs 21.1%), and Whole Body Itch NRS (45.5% vs 22.5%) response, and significantly greater DLQI improvement was observed versus placebo (-6.7 vs -3.8; all P < .0001). Common adverse events with apremilast were diarrhea (30.5%), nausea (21.5%), headache (12.0%), and vomiting (5.5%). LIMITATIONS: Patients with mild disease were not enrolled. CONCLUSION: Apremilast showed efficacy for the treatment of moderate to severe scalp psoriasis.

Pharmacokinetics and safety of apremilast in pediatric patients with moderate to severe plaque psoriasis: Results from a phase 2 open-label study.

BACKGROUND: No oral systemic treatments are approved for pediatric patients with psoriasis. OBJECTIVE: To evaluate the pharmacokinetics and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in pediatric patients with psoriasis. METHODS: This phase 2, multicenter, open-label study enrolled pediatric patients with moderate to severe plaque psoriasis. Patients received apremilast twice daily without titration for 2 weeks (group 1 [age, 12-17 years; weight, ≥35 kg]: apremilast 20 or 30 mg; group 2 [age, 6-11 years; weight, ≥15 kg]: apremilast 20 mg), followed by a 48-week extension. Primary endpoints were pharmacokinetics and safety. Other endpoints were taste/acceptability and change from baseline in score on the Psoriasis Area and Severity Index. RESULTS: A total of 42 enrolled patients (21 adolescents [age, 12-17 years] and 21 children [age, 6-11 years]) received apremilast. Pharmacokinetics modeling and noncompartmental analyses showed that weight-based dosing with apremilast 20 mg twice daily in children or apremilast 20 or 30 mg twice daily in adolescents provides exposure (area under the concentration-time curve from time 0 to 12 hours after the dose) that is comparable to that achieved with apremilast 30 mg twice daily in adults. The safety profile was generally similar to that in adults. Most study participants liked the taste of the tablet. Improvements from baseline in mean Psoriasis Area and Severity Index score were 68% for adolescents (overall) and 79% for children. LIMITATIONS: No children weighing less than 20 kg were enrolled. CONCLUSIONS: This first-time-in-children phase 2 study supports weight-based apremilast dosing for future phase 3 studies of pediatric plaque psoriasis.

Qualitative analysis and reproducibility assessment of the Scalp Itch Numeric Rating Scale among patients with moderate to severe plaque psoriasis of the scalp.

Background: Pruritus is a prevalent and bothersome symptom of scalp psoriasis. Validated scales assessing scalp itch are needed to evaluate treatment efficacy. Objective: To evaluate comprehensibility and reproducibility of the Scalp Itch Numeric Rating Scale (NRS), a novel scale being used in a phase 3 study of apremilast. Methods: The Scalp Itch NRS, Modified Whole Body Itch NRS, Global Assessment of Psoriasis Severity-Scalp (GAPS-S), and Global Impression of Change-Scalp Itch (GIC-SI) were assessed among patients with moderate to severe scalp psoriasis. Convergent validity and test-retest reliability between two visits (7 ± 3 days apart) were assessed using intra-class and Spearman's correlations. Results: Patients found the Scalp Itch NRS easy to use and understand. Convergent validity (Modified Whole Body Itch NRS Visit 1: rs = 0.71, Visit 2: rs = 0.92, p< .0001; GAPS-S Visit 1: rs = 0.62, Visit 2: rs = 0.63, p< .0001), and consistency with changes (Modified Whole Body Itch NRS: rs = 0.69, p< .0001; GAPS-S: rs = 0.42, p = .0029) were demonstrated. The Scalp Itch NRS showed strong test-retest reliability (intra-class correlation coefficient = 0.87; rs = 0.89). Change scores on the Scalp Itch NRS were consistent with change scores on the GIC-SI. Conclusions: The Scalp Itch NRS is a valid and reproducible measure of scalp itch in patients with moderate to severe scalp psoriasis. ClinicalTrials.gov: NCT03123471.