Long-term Efficacy and Safety of Up to 108 Weeks of Ixekizumab in Pediatric Patients With Moderate to Severe Plaque Psoriasis: The IXORA-PEDS Randomized Clinical Trial.

Importance: About 1% of children and adolescents worldwide are affected by plaque psoriasis. Objective: To evaluate the long-term efficacy and safety of ixekizumab for pediatric patients with moderate to severe psoriasis. Design, Setting, and Participants: This multicenter randomized clinical trial (IXORA-PEDS) evaluated pediatric patients with plaque psoriasis. Participants were aged 6 years to younger than 18 years; had moderate to severe psoriasis, which was defined as Psoriasis Area and Severity Index (PASI) of 12 or higher, static Physician's Global Assessment (sPGA) score of 3 or higher, and psoriasis-affected body surface area of 10% or greater at screening and baseline; were candidates for phototherapy or systemic therapy; or had psoriasis that was not adequately controlled by topical therapies. Data analysis, which followed the intention-to-treat principle, was conducted from May to October 2021. Interventions: Pediatric patients were randomized 2:1 to receive either a weight-based dose of ixekizumab every 4 weeks or placebo. After a 12-week placebo-controlled period, patients entered a 48-week, open-label ixekizumab maintenance period (weeks 12-60), followed by an extension period that lasted through 108 weeks. A substudy evaluated the randomized withdrawal of ixekizumab after week 60. Main Outcomes and Measures: Efficacy outcomes at week 108 included the percentage of patients achieving 75% (PASI 75), 90% (PASI 90), or 100% (PASI 100) improvement from baseline; an sPGA score of 0 or 1 or score of 0; and improvement of 4 points or higher from baseline in the Itch Numeric Rating Scale. Safety outcomes included assessments of adverse events (AEs), including treatment-emergent AEs, serious AEs, and AEs of special interest, as well as improvement from baseline in a range of challenging body areas. Missing data for categorical outcomes were imputed using modified nonresponder imputation. Results: A total of 171 patients (mean [SD] age, 13.5 [3.04] years; 99 female children [57.9%]) were randomized to either ixekizumab (n = 115) or placebo (n = 56). Of 166 patients who entered the maintenance period, 139 (83.7%) completed week 108 of the trial. Primary and gated secondary end points were sustained through week 108, with patients achieving PASI 75 (91.7% [n = 86]), PASI 90 (79.0% [n = 74]), PASI 100 (55.1% [n = 52]), sPGA 0 or 1 (78.3% [n = 74]), and sPGA 0 (52.4% [n = 49]). Fifty-five patients (78.5%) reported an Itch Numeric Rating Scale improvement of 4 points or higher. In patients who received ixekizumab, at week 108, clearance of nail psoriasis was reported in 68.1% (n = 28), clearance of palmoplantar psoriasis was reported in 90.0% (n = 10), clearance of scalp psoriasis was reported in 76.2% (n = 83), and clearance of genital psoriasis was reported in 87.5% (n = 24). There were no new safety findings during weeks 48 to 108 of the trial, including no new cases of inflammatory bowel disease or candida infection. Conclusions and Relevance: Results of this study showed improvements across patient-reported outcomes and objective measures of complete skin clearance of psoriasis among pediatric patients who received ixekizumab, and these response rates were sustained through week 108 of the trial. Safety of ixekizumab was consistent with previously reported findings in this population and the known safety profile of this treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT03073200.

Hirsutism: an evidence-based treatment update.

BACKGROUND: Hirsutism has a relatively high prevalence among women. Depending upon societal and ethnic norms, it can cause significant psychosocial distress. Importantly, hirsutism may be associated with underlying disorders and co-morbidities. Hirsutism should not simply be looked upon as an issue of cosmesis. Patients require appropriate evaluation so that underlying etiologies and associated sequelae are recognized and managed. Treatment of hirsutism often requires a multidisciplinary approach, and a variety of physical or pharmacologic modalities can be employed. Efficacy of these therapies is varied and depends, among other things, upon patient factors including the underlying etiology, hormonal drive, and local tissue sensitivity to androgens. OBJECTIVE: The objective of this paper is to review and summarize current evidence evaluating the efficacy of various treatment modalities for hirsutism in premenopausal women. METHODS: Online databases were searched to identify all relevant prior systematic reviews and meta-analyses as well as recently published (2012-present) randomized controlled trials (RCTs) on hirsutism treatment. RESULTS: Four recently published RCTs met criteria for inclusion in our review. In addition, one meta-analysis and one systematic review/treatment guideline were identified in the recent literature. Physical modalities and oral contraceptive pills (OCPs) remain first-line treatments. Evidence supports the use of electrolysis for permanent hair removal in localized areas and lasers (particularly alexandrite and diode lasers) for permanent hair reduction. Topical eflornithine can be used as monotherapy for mild hirsutism and as an adjunct therapy with lasers or pharmacotherapy in more severe cases. Combined OCPs as a class are superior to placebo; however, antiandrogenic and low-dose neutral OCPs may be slightly more efficacious in improving hirsutism compared with other types of OCPs. Antiandrogens are indicated for moderate to severe hirsutism, with spironolactone being the first-line antiandrogen and finasteride and cyproterone acetate being second-line antiandrogens. Due to its risk for hepatotoxicity, flutamide is not considered a first-line therapy. If used, the lowest effective dose should be administered with careful monitoring of liver enzymes. Monotherapy with an insulin sensitizer does not significantly improve hirsutism. While insulin sensitizers improve important metabolic and endocrine aberrations in polycystic ovary syndrome, they are not recommended when hirsutism is the sole indication for use. Lifestyle modification counseling is recommended. Gonadotropin-releasing hormone analogs and glucocorticoids are only recommended in specific circumstances. Additional therapies without sufficient supportive evidence of efficacy are ovarian surgery, statins (HMG-CoA reductase inhibitors), and vitamin D supplementation. LIMITATIONS: In general, most therapies garner recommendations that are weak (where the estimates of benefits versus risks of therapy are either closely balanced or uncertain) and are based on low- to moderate-quality evidence. CONCLUSIONS: Risks and benefits of treatment must be carefully considered and discussed with the patient. Expectations for efficacy should be appropriately set. A minimum of 6 months is required to see benefit from pharmacotherapy and lifelong treatment is often necessary for sustained benefit.