Managing pediatric psoriasis: update on treatments and challenges—a review

Figures & data

Table 1. Overview of approved and investigational biologics for the treatment of pediatric PsO.

Biologic (target)	Approval	Age of indication, years*	Weight-based dosing		Warnings
Etanercept (TNF-α) (9)	FDA	≥4	≥63 kg	50 mg qw	Discontinue for serious infection or sepsis Baseline evaluation for TB recommended
			<63 kg	0.8 mg/kg qw
	EMA	≥6	All patients	0.8 mg/kg qw
Ustekinumab (IL-12/IL-23) (10,11)	FDA and EMA	≥6	>100 kg	Initial: 90 mg on days 0 and 30	Serious infections from mycobacteria, Salmonella, and BCG vaccine have been reported in patients with IL-12/IL-23 deficiency Interstitial, eosinophilic, and cryptogenic organizing pneumonia have been reported Possible increased risk of malignancy and posterior leukoencephalopathy (1 suspected case report) Baseline evaluation for TB recommended
				Maintenance: 90 mg q12w
			60–100 kg	Initial: 45 mg on days 0 and 30
				Maintenance: 45 mg q12w
			<60 kg	Initial: 0.75 mg/kg on days 0 and 30
				Maintenance: 0.75 mg/kg q12w
Ixekizumab (IL-17A) (12)	FDA and EMA	≥6	>50 kg	Initial: 160 mg (80 mg × 2)	Crohn’s disease and ulcerative colitis, including exacerbations, occurred in clinical trials Baseline evaluation for TB recommended
				Maintenance: 80 mg q4w
			25–50 kg	Initial: 80 mg
				Maintenance: 40 mg q4w
			<25 kg^†	Initial: 40 mg
				Maintenance: 20 mg q4w
Secukinumab (IL-17A) (13,14)	FDA and EMA	≥6	≥50 kg	Load: 150 mg at weeks 0, 1, 2, 3, and 4	Baseline evaluation for TB recommended (adults); TBD for pediatric patients
				Maintenance: 150 mg q4w
			<50 kg	Load: 75 mg at weeks 0, 1, 2, 3, and 4
				Maintenance: 75 mg q4w
Adalimumab (TNF-α) (60,61)	FDA^‡	≥4	≥13 kg	Initial: 0.4 mg/kg (low) or 0.8 mg/kg (high) at weeks 0 and 1	Baseline evaluation for TB recommended (adults); TBD for pediatric patients
				Maintenance: 0.4 mg/kg (low) or 0.8 mg/kg (high) q2w
	EMA	≥4	≥30 kg	Initial: 40 mg at week 0
				Maintenance: 40 mg q2w
			15 kg to < 30 kg	Initial: 20 mg at week 0
				Maintenance: 20 mg q2w

BCG: bacille Calmette-Guérin; EMA: European Medicines Agency; FDA: United States Food and Drug Administration; IL: interleukin; PsO: psoriasis; q2w: every 2 weeks; q4w: every 4 weeks; q12w: every 12 weeks; qw: every week; TB: tuberculosis; TBD: to be determined; TNF: tumor necrosis factor.

*Age under investigation for investigational biologics.

^†The EMA does not recommend a dosage of ixekizumab for patients with body weight <25 kg.

^‡Adalimumab has not been approved by the FDA for pediatric PsO and is still under investigation.

Table 2. Summary of data from pediatric PsO clinical trials.

Biologic (sample size)	Weight-based dosing		Endpoints	Duration, weeks	Outcomes (active vs PBO/comparator)	Safety*
Etanercept (N = 211) (9)	≥63 kg	50 mg qw	PASI75	12	57% vs 11%	Etanercept: 4 SAEs (3 infections) PBO: 0
	<63 kg	0.8 mg/kg qw
Ustekinumab (N = 44 patients aged 6 to < 12 years) (10)	>100 kg	Initial: 90 mg on d 0 and 30 Maintenance: 90 mg q12w	PGA 0/1 PASI75 PASI90 Mean change in CDLQI	12	77% 84% 64% −6.3	3 SAEs
	60–100 kg	Initial: 45 mg on d 0 and 30 Maintenance: 45 mg q12w
	<60 kg	Initial: 0.75 mg/kg on d 0 and 30 Maintenance: 0.75 mg/kg
Ustekinumab (N = 110 patients aged 12–17 years) (11)	>100 kg	SD: Initial: 90 mg on d 0 and 30 Maintenance: 90 mg q12w HSD: Initial: 45 mg on d 0 and 30 Maintenance: 45 mg q12w	PGA 0/1 PASI75 PASI90 Mean change in CDLQI	12	69.4% (SD), 67.6% (HSD) vs 5.4% 80.6% (SD), 78.4% (HSD) vs 10.8% 61.1% (SD), 54.1% (HSD) vs 5.4% −6.7 (SD), −5.6 (HSD), −1.5	SD: 1 patient with ≥ 1 SAE HSD: 5 patients with ≥ 1 SAE PBO (through week 12): 0 patients with ≥ 1 SAE
	60–100 kg	SD: Initial: 45 mg on d 0 and 30 Maintenance: 45 mg q12w HSD: Initial: 22.5 mg on d 0 and 30 Maintenance: 22.5 mg q12w
Ixekizumab (N = 199) (12)	>50 kg	Initial: 160 mg (80 mg × 2) Maintenance: 80 mg q4w	sPGA 0/1 PASI75	12	81% vs 11% 89% vs 25%	Ixekizumab: 13 SAEs PBO (through week 12): 0 SAEs
	25–50 kg	Initial: 80 mg Maintenance: 40 mg q4w
	<25 kg	Initial: 40 mg Maintenance: 20 mg q4w
Secukinumab (N = 162) (13)	≥50 kg	Load: 150 mg (low) or 300 mg (high) qw × 4 Maintenance: 150 mg (low) or 300 mg (high) q4w	PASI75 PASI90 PASI100 IGA mod 2011 0/1	12	80.0% (low), 77.5% (high), 14.6% (PBO) 72.5% (low), 67.5% (high), 2.4% (PBO) 30.0% (low), 27.5% (high), 0% (PBO) 70.0% (low), 60.0% (high), 4.9% (PBO)	Any low (through week 52): 5 SAEs Any high (through week 52): 5 SAEs
	25-<50 kg	Load: 75 mg (low) or 150 mg (high) qw × 4 Maintenance: 75 mg (low) or 150 mg (high) q4w
	<25 kg	Load: 75 mg (both low and high) qw × 4 Maintenance: 75 mg (both low and high) q4w
Secukinumab (N = 84) (14)	≥50 kg	Load: 150 mg (low) or 300 mg (high) qw × 4 Maintenance: 150 mg (low) or 300 mg (high) q4w	PASI75 PASI90 PASI100 IGA mod 2011 0/1	12	92.9% (low), 92.9% (high) 69.0% (low), 76.2% (high) 59.5% (low), 54.8% (high) 78.6% (low), 81.0% (high)	Low (through week 16): 1 SAE High (through week 16): 0 SAEs
	25-<50 kg	Load: 75 mg (low) or 150 mg (high) qw × 4 Maintenance: 75 mg (low) or 150 mg (high) q4w
	<25 kg	Load: 75 mg (both low and high) qw × 4 Maintenance: 75 mg (both low and high) q4w
Adalimumab vs MTX (N = 224) (60,61)	≥13 kg	Initial: 0.4 mg/kg (low) or 0.8 mg/kg (high) at weeks 0 and 1 Maintenance: 0.4 mg/kg (low) or 0.8 mg/kg (high) q2w MTX: 0.1–0.4 mg/kg qw	PASI75 PGA 0/1	16	58% vs 32% 61% vs 41%	Adalimumab: 3 SAEs PBO (through week 16): 0 SAEs

CDLQI: Children’s Dermatology Life Quality Index; d: days; FDA: United States Food and Drug Administration; HSD: half standard dose; IGA mod: Investigator’s Global Assessment modified; MTX: methotrexate; PASI: Psoriasis Area and Severity Index; PBO: placebo; PGA: Physician’s Global Assessment; PsO: psoriasis; q2w: every 2 weeks; q4w: every 4 weeks; q12w: every 12 weeks; qw: every week; SAE: serious adverse event; SD: standard dose; sPGA: static Physician’s Global Assessment.

*Safety is reported through the end of the study unless otherwise indicated.

Table 3. Other considerations for biologics in pediatric patients with PsO.

Biologic (target)	Administration route and maintenance dose frequency*	How supplied	Other pediatric indications	Safety considerations of interest
Approved
Etanercept (TNF-α)	SC qw	Single-dose prefilled syringe, single-dose autoinjector (SureClick^®, Immunex Corporation, Thousand Oaks, CA), reusable single-dose autoinjector (AutoTouch^®, Immunex Corporation, Thousand Oaks, CA), single-dose vial, or multiple-dose vial	JIA	CHF
				Hematologic reactions
				Hepatitis B reactivation
				ISRs
				Malignancies in adults
				Neurological reactions
Ustekinumab (IL-12/IL-23)	SC q12w	Single-dose vial or single-dose prefilled syringe	Crohn’s disease	Hypersensitivity
				Infections
	IV q12w	Single-dose vial		Immunogenicity
				Malignancy in adults
				Noninfectious pneumonia
				Reversible posterior leukoencephalopathy
				Not effective for spondyloarthritis
Ixekizumab (IL-17A)	SC q4w	Single-dose autoinjector or prefilled syringe	–	ISRs
				IBD
				Tinea
				Upper respiratory infections
				Hypersensitivity
Secukinumab (IL-17A)	SC q4w	Single-dose prefilled syringe, autoinjector Sensoready^® pen (Novartis AG, Basel, Switzerland), or single-dose vial	–	IBD
				Upper respiratory infections
				Hypersensitivity
Adalimumab^† (TNF-α)	SC q2w	Single-dose prefilled pen (Humira^® Pen, AbbVie, Inc, North Chicago, IL) or prefilled glass syringe	JIA Crohn’s disease Adolescent HS	Cytopenias and pancytopenia
				Demyelinating disease
				Heart failure
				Hematologic reactions
				Hepatitis B reactivation
				Lupus-like syndrome
				Malignancies in adults
Under investigation
Brodalumab (IL-17RA)	SC q2w	Single-dose prefilled syringe	–	Crohn’s disease
				Suicidal ideation and behavior
				Tinea
				Influenza
				Neutropenia
Guselkumab (IL-23)	SC q8w	Single-dose prefilled syringe or autoinjector	–	ISRs
				Tinea
				Upper respiratory infections
				Gastroenteritis
				Herpes simplex infection
				Hypersensitivity
Tildrakizumab (IL-23)	SC q12w	Single-dose prefilled syringe	–	ISRs
				Upper respiratory infections
				Hypersensitivity
Risankizumab (IL-23)	SC q12w	Single-dose prefilled syringe	–	ISRs
				Tinea
				Upper respiratory infections
				Hypersensitivity

CHF: chronic heart failure; FDA: United States Food and Drug Administration; HS: hidradenitis suppurativa; IBD: inflammatory bowel disease; IL: interleukin; ISR: injection site reaction; IV: intravenous; JIA: juvenile idiopathic arthritis; PsO: psoriasis; q2w: every 2 weeks; q4w: every 4 weeks; q8w: every 8 weeks; q12w: every 12 weeks; qw: every week; SC: subcutaneous; TNF: tumor necrosis factor.

*Administration frequency after the loading dose, where applicable.

^†Adalimumab has been approved for pediatric PsO by the EMA but not the FDA.

Table 4. Resources for patients and providers for accessing biologic treatment in pediatric PsO.

Resource organization	Link
National Psoriasis Foundation	https://www.psoriasis.org/health-care-providers/working-with-health-plans. https://www.psoriasis.org/access-care/insurance/financial-assistance/biologics.
United States Food and Drug Administration	https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber/expanded-access-experimental-biologics.
Society for Pediatric Dermatology	https://pedsderm.net/.
Journal of the American Academy of Dermatology	https://www.jaad.org/article/S0190-9622(19)32655-6/fulltext.

PsO: psoriasis.

Paller AS, Siegfried EC, Langley RG, et al. Etanercept treatment for children and adolescents with plaque psoriasis. N Engl J Med. 2008;358(3):241–251.

 PubMed Web of Science ®Google Scholar

Philipp S, Menter A, Nikkels AF, et al. Ustekinumab for the treatment of moderate-to-severe plaque psoriasis in paediatric patients (≥6 to <12 years of age): efficacy, safety, pharmacokinetic and biomarker results from the open-label CADMUS Jr study. Br J Dermatol. 2020;183(4):664–672.

 PubMed Web of Science ®Google Scholar

Landells I, Marano C, Hsu MC, et al. Ustekinumab in adolescent patients age 12 to 17 years with moderate-to-severe plaque psoriasis: results of the randomized phase 3 CADMUS study. J Am Acad Dermatol. 2015;73(4):594–603.

 PubMed Web of Science ®Google Scholar

Paller AS, Seyger MMB, Magariños GA, et al. Efficacy and safety of ixekizumab in a phase 3, randomized, double-blind, placebo-controlled study in paediatric patients with moderate-to-severe plaque psoriasis (IXORA-PEDS). Br J Dermatol. 2020;183(2):231–241.

 PubMed Web of Science ®Google Scholar

Bodemer C, Kaszuba A, Kingo K, et al. Secukinumab demonstrates high efficacy and a favourable safety profile in paediatric patients with severe chronic plaque psoriasis: 52-week results from a phase 3 double-blind randomized, controlled trial. J Eur Acad Dermatol Venereol. 2021;35(4):938–947.

 PubMed Web of Science ®Google Scholar

Magnolo N, Kingo K, Laquer V, et al. Secukinumab is highly efficacious and has a favorable safety profile in pediatric patients with moderate-to-severe plaque psoriasis. American Academy of Dermatology 2020; E-Congress 2020.

 Google Scholar

Thaçi D, Papp K, Marcoux D, et al. Sustained long-term efficacy and safety of adalimumab in paediatric patients with severe chronic plaque psoriasis from a randomized, double-blind, phase III study. Br J Dermatol. 2019;181(6):1177–1189.

 PubMed Web of Science ®Google Scholar

Papp K, Thaci D, Marcoux D, et al. Efficacy and safety of adalimumab every other week versus methotrexate once weekly in children and adolescents with severe chronic plaque psoriasis: a randomised, double-blind, phase 3 trial. Lancet. 2017;390(10089):40–49.

 PubMed Web of Science ®Google Scholar