Pediatric psoriasis: Biologics and oral small molecule inhibitors in modern therapy

Abstract

Therapeutic options are expanding for pediatric patients with psoriasis. Here, we offer an overview of the current treatment landscape for pediatric psoriasis, focusing on the increasing role of biologics and oral small molecules. Each therapeutic is discussed in terms of dosage, safety profile, and assessment through measures such as the Psoriasis Area Severity Index and the Children’s Dermatology Life Quality Index, where data are available. We highlight the important pediatric-specific clinical trials as well as infer potential for pediatric therapy based on available adult trials. There has been a steady increase in pediatric psoriasis trials, but there is a continued need for more pediatric-focused research. Additional trials and therapeutics that match adult trials would substantially refine therapeutic decision-making and improve outcomes in this demographic.

INTRODUCTION

Psoriasis is a chronic immune-mediated skin disorder influenced by both environmental and genetic factors. It often presents for the first time in childhood and affects about 0.5% to 2% of the pediatric population.^1–8 In children, psoriasis frequently manifests on the face, scalp, and extensor surfaces of the elbow and knee.^9,10 Even in children, psoriasis may coexists with arthritis, obesity, and cardiometabolic disease which further complicate management.^3,5,11,12 The stigmatization of the disease can lead to social isolation, depression, and anxiety.^2,5

Early detection and tailored therapeutic strategies are crucial for mitigating the impact on a child. Initial therapy for mild-to-moderate disease often involves topical medications: steroids, calcineurin inhibitors, phosphodiesterase inhibitors and vitamin D analogues, as well as coal tar preparations, anthralin, and salicylic acid as adjunctive therapy.^5,13 Phototherapy (Narrow Band Ultraviolet B 311–313 nm) is another option that may be considered in those with mild to moderate disease.^3,5,7 The excimer laser (308 nm) provides targeted phototherapy to treat localized disease.^5,9 Combined therapies such as calcipotriol with betamethasone dipropionate are Food and Drug Administration (FDA)-approved to treat body and scalp psoriasis in children 12 years and older and improve compliance due to ease of use.^5,14

Systemic therapy is utilized when topical and light therapy are not effective, the disease progresses, there is comorbid arthritis, or when there are negative impacts on quality of life. Conventional systemic medications such as methotrexate, cyclosporine, and acitretin have historically been prescribed off-label as monotherapy or in combination with topicals and/or light therapy. These medications are approved for other pediatric conditions such as juvenile idiopathic arthritis, and organ transplantation, respectively.^15–17

2020 guidelines from the Joint American Academy of Dermatology-National Psoriasis Foundation have provided a framework for the management and treatment of psoriasis in pediatric patients.⁵ Still, there are limited but growing clinical trial data. Biologic agents and targeted oral small molecules (OSMs)^18,19 have revolutionized the therapeutic framework for psoriasis in the past few decades, exhibiting substantial efficacy in adult and pediatric populations.^8,20

Below biologic agents and OSMs for pediatric psoriasis are reviewed, with a focus on effectiveness assessed by Psoriasis Area and Severity Index (PASI) scores, which measure lesion severity and involved body surface area (higher scores indicate more severe disease) (Table I). PASI 50, represents a 50% improvement in symptoms, PASI 75 (75% improvement), and PASI 90 (90% improvement). The impact of treatments on patients’ quality of life using the Children’s Dermatology Life Quality Index (CDLQI) is also considered. A literature search using PubMed assessing the last 10 years using keywords “pediatric psoriasis,” “biologics,” “small molecules,” “management,” “treatment,” and “guidelines” was conducted. Phase II or higher clinical trials for the last 10 years were also reviewed.

Table I.

Biologics approved for pediatric psoriasis

Class	Drug	Approved age by		Year of approval by		NCT number	Dose
		FDA	EMA	FDA	EMA
TNF-alpha inhibitors	Etanercept	≥4 y	≥6 y	2016	2011	NCT00141921 NCT01100034 NCT00078819 NCT02471144	0.8 mg/kg given once weekly or 0.4 mg/kg twice weekly up to a max dose of 50 mg/wk
	Adalimumab	Not approved	≥4 y	Not approved	2015	NCT01251614 NCT03925441 NCT04018599	0.8 mg/kg given at wk 0 and 1 and then every other wk to a max dose of 40 mg
IL-12 and IL-23 inhibitors	Ustekinumab	≥6 y		2022	2019	NCT01090427 NCT02698475	0.75 mg/kg (<60 kg) 45 mg (60 to 100 kg) 90 mg (>100 kg) given at wk 0 and 4 and then every 12 wk
IL-17A inhibitors	Ixekizumab	≥6 y		2020		NCT03073200	40 mg (<25 kg) at k 0 and then 20 mg every 4 wk
							80 mg (25 to 50 kg) at wk 0 and then 40 mg every 4 wk
							160 mg (>50 kg) at wk 0 and then 80 mg every 4 wk
	Secukinumab	≥6 y		2021	2020	NCT02471144	75 mg (<50 kg) 150 mg (≥50 kg) given at wk 0, 1, 2, 3, 4 and then every 4 wk
PDE4 inhibitors	Apremilast	≥6 y		2024		NCT03701763	20 mg twice a d (>20 kg- <50 kg) 30 mg twice a d (≥50 kg)

The table above features a list of biologic agents approved for pediatric psoriasis treatment, highlighting FDA and EMA approved age ranges, approval years, National Clinical Trial (NCT) numbers, and recommended dosing. Baseline blood work includes tuberculosis testing prior to starting, and yearly thereafter, while on the medication for all medications except Apremilast.

EMA, European Medicines Agency; FDA, Food and Drug Administration.

BIOLOGICS

Tumor necrosis factor (TNF)-alpha inhibitors

Etanercept.

Etanercept was first approved by the FDA in children ages 4 and older with plaque psoriasis in November 2016.²¹ Etanercept functions as a human fusion protein binding to and blocking TNF-α.⁶ Weekly dose is subcutaneous injection of 0.8 mg/kg, adjusted to a maximum dose of 50 mg for those weighing 63 kg. In children and adolescents with moderate-to-severe plaque psoriasis, etanercept significantly reduced disease severity (achieved PASI 50, 75, and 90 at 12 weeks) and this maintained through the 96-week extension study.²² Quality of life improvements (CDLQI) were more pronounced for etanercept than placebo at 12 weeks, achieving statistical significance.²³ Though upper respiratory tract infections, nasopharyngitis, and mild, tolerable injection site reactions or pain were noted, no serious adverse events were reported. During the 264-week follow-up period, few participants withdrew due to adverse events, and there were no recorded instances of deaths or malignancies.²² Etanercept has the longest history of use in the pediatric population which contributes to its widespread use.^2,11

Adalimumab.

Adalimumab is a fully human monoclonal IgG1 antibody targeting TNF-α, binding both its soluble and membrane-bound forms.^16,19,24 While not approved by the United States FDA for pediatric psoriasis, it was approved by the European Medicines Agency (EMA) in 2015 for children as young as 4 years specifically for psoriasis cases unresponsive to topical treatments and phototherapy.¹⁶ Adalimumab is administered at a dose of 0.8 mg/kg at weeks 0 and 1 and is then given every other week up to a maximum dose of 40 mg.²⁵ In a comparison between methotrexate and adalimumab for severe plaque psoriasis in children and adolescents, those treated with adalimumab reached significant outcomes with PASI 50 and PASI 75 but not PASI 90 by week 16 and experienced better quality of life outcomes with sustained efficacy over 52 weeks. It should be noted that the average dose of methotrexate used in the study was below the typical dose for pediatric psoriasis. The safety profile of adalimumab did not differ significantly from that of methotrexate, and no additional safety concerns were identified.²⁵ The most frequent adverse effects were nasopharyngitis and headache, followed by injection site reaction.²⁴ With the availability of TNF-α inhibitors like adalimumab at lower costs, access to these treatments has markedly increased, offering more accessible options for patients.

Interleukin (IL)-12 and IL-23 inhibitors

Ustekinumab.

Ustekinumab is a fully human monoclonal antibody that targets and inhibits the p40 protein subunit found in both IL-12 and IL-23 cytokines.^5,26 Ustekinumab has received approval from both the EMA and FDA for treating moderate-to-severe plaque psoriasis in patients aged 6 years and older.¹² The recommended dose of ustekinumab is 0.75 mg/kg for patients weighing less than 60 kg, 45 mg for those between 60 to ≤100 kg, and 90 mg for those above 100 kg, with doses given at week 0, 4, and 16 and then every 12 weeks.¹ In the multicenter CADMUS study (adolescents aged 12–17), ustekinumab significantly reduced plaque psoriasis severity, achieving PASI 50, 75, and 90 scores at 12 weeks, while also enhancing QoL as measured by the CDLQI with benefits largely sustained through 52 weeks.¹ Main adverse events linked to ustekinumab were nasopharyngitis, pharyngitis, upper respiratory tract infections, headaches, and injection site reactions.²⁶ The decreased dosing frequency compared to other biologic agents, enhances patient compliance and QoL.²⁶

IL-17A inhibitors

Ixekizumab.

Ixekizumab, a high-affinity monoclonal antibody selectively targeting interleukin-17A, received approval from the FDA and EMA in 2020 for treating moderate-to-severe psoriasis in patients aged 6 years and older.² Dosing of ixekizumab for pediatric psoriasis varies according to weight. In one clinical trial, participants over 50 kg received an initial dose of 160 mg, followed by a maintenance dose of 80 mg every 4 weeks up to week 8. For those between 25 and 50 kg, the initial dose was 80 mg, followed by maintenance dosing of 40 mg every 4 weeks until week 8. Participants weighing up to 25 kg were given an initial dose of 40 mg, followed by maintenance dosing of 20 mg every 4 weeks through week 8. At week 12, patients treated with ixekizumab demonstrated statistically significant improvements in both PASI 75 and PASI 90 scores compared to placebo and. These benefits were sustained and further improved in PASI 75 rates through week 48. Significant enhancements in CDLQI scores were observed at week 12 and were sustained or further improved through week 48. Ixekizumab was generally well-tolerated, yielding no severe treatment-emergent adverse events. Four patients had treatment-emergent inflammatory bowel disease, leading to discontinuation.¹¹

Secukinumab.

Secukinumab is a fully human monoclonal IgG1 antibody that selectively targets IL-17A. It received approval from both the FDA and EMA in 2020 for the treatment of moderate-to-severe plaque psoriasis in children aged 6 and older at a recommended weight-based dosing of 75 mg for patients weighing less than 50 kg and 150 mg for those weighing 50 kg or more administered at weeks 0, 1, 2, 3, 4, and then every 4 weeks thereafter. In a pediatric psoriasis clinical trial, secukinumab was administered based on a weight-stratified dosing regimen. Specifically, patients weighing less than 25 kg received 75 mg in both the low-dose and high-dose groups. For those weighing between 25 and 50 kg, the low-dose group received 75 mg and the high-dose group received 150 mg. Patients weighing over 50 kg were administered 150 mg in the low-dose group and 300 mg in the high-dose group. The study achieved its primary endpoint, showing statistically significant improvements in PASI 75 response rates for both low-dose and high-dose secukinumab compared to placebo and etanercept, starting as early as week 4 and sustained through week 52. Both secukinumab groups outperformed placebo and etanercept by week 12 in PASI 90 responses. Across visits up to week 52, secukinumab-treated groups maintained statistically significant higher PASI response rates compared to etanercept. CDLQI scores also improved. The safety profile of secukinumab was generally comparable to that of etanercept. Medications targeting IL-17, such as secukinumab and ixekizumab, may exacerbate inflammatory bowel disease, with reported cases ranging from 0% to 1.5% in pediatric clinical studies and should be avoided in patients with a confirmed inflammatory bowel disease diagnosis.² Nonspecific gastrointestinal symptoms should be evaluated prior to initiation.

ORAL SMALL MOLECULES

Phosphodiesterase 4 inhibitor

Apremilast is a phosphodiesterase 4 inhibitor that has been approved for the treatment of adult patients with psoriasis and received approval in children 6–17 in August of 2024.^27,28 The Sprout clinical trials (NCT02576678, NCT03701763) showed apremilast was safe and effective in reducing psoriasis over a 16 week period in children 6–17.²⁹ 45% reached a PASI 75 and 24% reached a PASI 90 at 16 weeks. Dosage recommendations for pediatric patients are weight-based, with all children and adolescents weighing between 35 and 70 kg receiving 20 mg twice daily, and those weighing over 70 kg receiving 30 mg twice daily. The drug was generally well-tolerated, with common adverse events being headache, gastrointestinal issues, and pharyngitis. The taste of the apremilast tablets was generally well-received by pediatric patients in the study.¹⁷ One case report involving a 14-year-old male reported successful treatment outcomes with adult dosages of apremilast, further supporting its potential utility in pediatric psoriasis treatment.³⁰ There have been case reports of patients experiencing psychiatric symptoms with apremilast including depression and suicidal ideation.^31,32 Additional research, including an ongoing study phase 3 clinical trial (NCT04175613) expected to conclude in 2027, aim to provide more comprehensive long-term data on the safety and efficacy of apremilast in this younger population.

Tyrosine kinase 2 inhibitor

Deucravacitinib.

Deucravacitinib is an oral tyrosine kinase 2 inhibitor that was approved for treating adult psoriasis in 2022. In adult studies, deucravacitinib has been administered at dosages ranging from 3 mg to 12 mg, taken once or twice daily. Adult patients on deucravacitinib showed significantly higher response rates versus placebo or apremilast for PASI 75 at week 16. Notably, secondary outcomes also reflected positively in terms of achieving higher PASI 90 and PASI 100 rates.³³ As for its impact on quality of life, studies have reported encouraging improvements based on the DLQI. In terms of adverse effects, the medication was generally well-tolerated, with nasopharyngitis and upper respiratory tract infections being the most reported issues.^34,35 Rates of discontinuation due to adverse effects were lower in the deucravacitinib cohorts compared to placebo and other treatment arms like apremilast.^33–35 The promising results have led to the initiation of further trials exploring the drug’s efficacy for different forms of psoriasis. An ongoing phase 3 clinical trial for pediatric psoriasis (NCT04772079), aims to provide more definitive data on the safety and efficacy of this drug in children and adolescents.

Additional takeaways

Research on the efficacy and safety of anti-psoriatic treatments is currently underway, with 12 active phase 2 and higher clinical trials focused on pediatric patients. These trials are examining a variety of systemic therapies, such as TNF-alpha inhibitors, IL-12 and IL-23 modulators, IL-17, phosphodiesterase 4 inhibitors, and tyrosine kinase 2 inhibitors. The findings from these studies are anticipated to offer crucial data that could substantially broaden the available treatment options for psoriasis in this distinct patient population. For details on ongoing clinical trials, please refer to Table II.

Table II.

Ongoing pediatric psoriasis clinical trials

Class	Drug	Trial	Phase
TNF-alpha inhibitors	Certolizumab Pegol	NCT04123795	Phase 3
IL-12 and IL-23 inhibitors	Risankizumab	NCT04435600	Phase 3
		NCT04862286	Phase 3
	Guselkumab	NCT03451851	Phase 3
	Tildrakizumab	NCT03997786	Phase 2/3
IL-17A inhibitors	Secukinumab	NCT03668613	Phase 3
	Brodalumab	NCT03240809	Phase 4
PDE-4 inhibitor	Apremilast	NCT04175613	Phase 3
		NCT05565560	Phase 3
		NCT02576678	Phase 2
TYK2 inhibitor	Deucravacitinib	NCT04772079	Phase 3

CONCLUSION

This review offers an overview of the evolving treatment landscape for pediatric psoriasis. Therapeutic options range from traditional methods like light therapy, topicals, and systemic agents. Improved data from clinical trials in pediatric patients allow for more options, especially for those who have not responded to conventional therapies, or those dealing with rapidly progressing disease, psychological distress, or comorbid conditions. Importantly, an unsuccessful response to one biologic does not rule out the possibility of a positive outcome with another, even within the same class. Treatment choices should be individualized to the clinical situation of each patient, considering factors such as disease severity, comorbidities, and potential for adverse effects.

Several barriers including cost, logistics of administration and availability still impede the integration of new treatments into routine care. While less frequent dosing and fewer laboratory tests may enhance compliance for some biologics, the requirements for refrigeration and specialized shipping can limit accessibility. On the other hand, the oral administration of targeted small molecule therapies, ease of initiation and cessation, and flexible dosing options make them suitable for short-term or seasonal treatments.

Prior to initiation, vaccinations should be up to date because live and attenuated vaccines may not be suitable during treatment. Monitoring for infections, especially upper respiratory infections, is recommended due to an increased risk associated with both biologic therapy and OSMs. Baseline monitoring should include tests for latent tuberculosis for all biologics except aprelimast (Table I) and screenings like hepatitis and HIV should be conducted based on individual risk factors. Though no standard lab tests are universally required, personalized considerations, such as comorbidities and treatment transitions, should guide clinical decision-making. For OSMs like deucravacitinib, the risk of viral reactivation, acne, and clotting should be among the side effects discussed before initiation.

There is a need for head-to-head comparisons between different biologics and between biologics and oral small molecules. Trials focusing specifically on the youngest patients are particularly needed. Treatment decisions should be rooted in current and reliable evidence to provide the most benefit for the pediatric patients they serve.

CAPSULE SUMMARY.

• Focused review of available treatments for pediatric psoriasis.

• Enables clinicians to understand the framework for management and use newer approved biologics and oral small molecules for their pediatric patients.

Abbreviations used:

CDLQI

Children’s Dermatology Life Quality Index

EMA

European Medicines Agency

FDA

Food and Drug Administration

PASI

Psoriasis Area and Severity Index

OSMs

oral small molecules