There are three key considerations that should be reviewed prior to placing pediatric patients on systemic therapy. These include 1) the severity of the disease, 2) lack of response to topical medications, and 3) impact on quality-of-life. As this population is especially prone to social interactions/social stigma, the high visibility of the disease makes this aspect of particular importance.

Systemic interventions indicated for children and adolescents affected by psoriasis are:

• Phototherapy (compliance in kids is difficult)
• Methotrexate
• Retinoids
• Cyclosporine
• Biologics: etanercept (approved by FDA 11/16), adalimumab (not yet FDA-approved) and ustekinumab (approved by FDA 10/17).

Methotrexate is commonly used in the United States where physicians have had decades of experience using it in children. Dosage is typically 0.2-0.5 mg/kg/week, which can be adjusted upwards for increased efficacy. However, the lowest effective dose should be maintained after tapering for safety reasons. In a recent study of 85 children, 34.1% achieved a Psoriasis Area Severity Index (PASI) 75 (time course not given) and had a drug survival of 21.1% at 1 year and 6.8% at 2 years.¹ It is also important to prepare a patient prior to the initiation of methotrexate therapy such as updating vaccines, checking labs, performing tuberculosis (TB) testing, and providing pregnancy counseling. Lastly, methotrexate may take many months to achieve the best effect. A single-site prospective study in 25 children showed that a PASI 50 was obtained in ~40% of the patients at 12 weeks of treatment, while ~40% and 80% achieved PASI 75 and PASI 50 by 36 weeks, respectively.² Folate supplementation is often used to ameliorate methotrexate-associated side effects and toxicities. Folic acid administration 6 or 7 times per week was more protective against methotrexate-induced gastrointestinal adverse events such as nausea or dyspepsia than did weekly administration.³

Retinoid (usually acitretin) is considered the first-line agent for pustular psoriasis in children, but also a favorite agent in some forms of psoriasis and palmoplantar psoriasis. Retinoids are commonly prescribed in Europe, but their use is very geographically diverse. In a study of 154 children in France a PASI 75 was achieved in 33.1% in 3 months,⁴ while in another study of 18 patients in Italy a PASI 75 was obtained in 44.4% at 16 weeks of treatment.⁵

Dosage is typically 0.2-0.5 mg/kg/day (max of 0.6 mg/kg/day) and should be tapered down to maintain the lowest effective dose. Retinoids do not cause immunosuppression and may be stopped and restarted without the loss of efficacy. Potential side effect of retinoid therapy is primarily skin and mucosal dryness. Patients also tend to be more adherent to retinoid therapy vs other therapies such as methotrexate.¹ Retinoids can also be used as an adjunctive therapy with phototherapy and other agents, such as , methotrexate, cyclosporine, and biologics.

Cyclosporine should l be considered as an option because it has consistently shown good responses for plaque, pustular, and erythrodermic psoriasis. However, because of its potential toxicity, many physicians choose to minimize its use. In addition, there was also a low drug survival with 15%, 5.5%, and 0% in 80 patents on cyclosporine at years 1, 2, and 3, respectively.¹ A PASI 75 was achieved after 3 months in 40% of the patients who were treated with cyclosporine.¹ Dosage is typically 3-5 mg/kg/day and it can be titrated up based on tolerance. The risks of toxicity include immunosuppression, hypertension, liver and renal disease, and should be carefully monitored in all patients on cyclosporine therapy.^1,6

TNF inhibitors, such as etanercept and adalimumab, are the primary option for biologic therapy in adults. Unfortunately, not many of these treatments have been tested specifically in pediatric patients.

Five-year safety and efficacy data is available for the now approved etanercept. Of the 181 patients enrolled initially, 69 patients completed the trial after 5 years.⁷ Etanercept in pediatric patients was generally well tolerated and efficacy was maintained in those who remained in the study. Maintenance with etanercept demonstrated a PASI 75 response of 60-70% at 5 years and a PASI 90 response of 30-40%. The benefits of this approval are two-fold because now patient assistance and home nurse programs are options for pediatric patients.

Adalimumab is another biologic that has shown efficacy in pediatric patients with moderate-to-severe psoriasis. In a study comparing adalimumab (0.8 mg/kg or 0.4 mg/kg subcutaneously) to methotrexate (0.1-0.4 mg/kg) over a 16-week period, 58% of patients (aged ≥4 to <18 years) in the adalimumab 0.8 mg/kg group reached PASI 75 compared to 44% in the adalimumab 0.4 mg/kg group and 32% in the methotrexate group (P=0.02679) at week 16.⁸ Therefore, treatment with adalimumab 0.8 mg/kg in children and adolescents with severe plaque psoriasis provided significant improvements in PASI 75 compared with methotrexate and adalimumab 0.4 mg/kg.

Ustekinumab, an interleukin-12 and interleukin-23 inhibitor, was approved for the treatment of psoriasis in pediatric patients. In the randomized phase 3 CADMUS study, 110 patients (age 12 to 17 years) were randomly assigned to ustekinumab standard dosing (SD; 0.75 mg/kg [≤60 kg], 45 mg [>60-≤100 kg], and 90 mg [>100 kg]) or half-standard dosing (HSD; 0.375 mg/kg [≤60 kg], 22.5 mg [>60-≤100 kg], and 45 mg [>100 kg]) or placebo at weeks 0 and 4 with crossover to ustekinumab SD or HSD at week 12.⁹ Significantly greater proportions receiving ustekinumab achieved PASI 75 (80.6% of SD, 78.4% of HSD and 10.8% of placebo) or PASI 90 (61.1% of SD, 54.1% of HSD and 5.4% of placebo) at week 12 (P<0.001).