Näytönastekatsaukset

Effectiveness of dupilumab compared to placebo in treatment of children with atopic dermatitis

Näytönastekatsaukset

30.5.2023

Raija Sipilä and Jorma Komulainen

Level of evidence: B

In children (6-11 years) with severe atopic dermatitis dupilumab (100 mg every two weeks for children with weight of 15 to <30 kg and 200 mg every two weeks for children with weight of ≥30 kg) with topical corticosteroids appears to increase the proportion of patients reaching EASI-75 at week 16 when compared to placebo (67–70% vs. 27%).

In addition, there is evidence that compared to placebo dupilumab may increase proportion of patients with IGA 0 or 1 and reduce pruritus. The evidence is based on 1 RCT with low risk of bias.

Table 1. Description of the included studies
Reference	Study type	Population	Intervention and comparison	Outcomes	Risk of bias
RCT=randomized controlled trial; BSA= body surface area, IGA=Investigator's Global Assessment); EASI=Eczema Area and Severity Index; NRS=weekly averaged baseline worst itch score, Peak Pruritus Numerical Rating Scale; TCS= topical corticosteroids; q2w=every 2 weeks; q4w= every 4 weeks
«Paller AS, Siegfried EC, Thaçi D ym. Efficacy and safety of dupilumab with concomitant topical corticosteroids in children 6 to 11 years old with severe atopic dermatitis: A randomized, double-blinded»1	RCT	Children age 6-11 years with atopic dermatitis (American Academy of Dermatology consensus criteria 20) diagnosed ≥ 1 year before screening; IGA score of 4, EASI score ≥ 21, affected BSA ≥ 15%, NRS ≥ 4; weight ≥ 15 kg; and documented history of inadequate response to topical medication within 6 months of baseline. N=367	Q2w: dupilumab + TCS every 2 weeks; q4w: dupilumab + TCS every 4 weeks; matching placebo + TCS	Primary: proportion of patients with an IGA score of 0 or 1; >75% improvement in EASI (EASI-75). Secondary: percent change in EASI and weekly average of peak pruritus NRS. Follow-up time 16 weeks.	low

Table 2. Additional comments for included studies
Reference	Comments
EASI=Eczema Area and Severity Index; TCS= topical corticosteroids; q2w= every 2 weeks; q4w= every 4 weeks
«Paller AS, Siegfried EC, Thaçi D ym. Efficacy and safety of dupilumab with concomitant topical corticosteroids in children 6 to 11 years old with severe atopic dermatitis: A randomized, double-blinded»1	Patients had severe atopic dermatitis (EASI ≥ 21) and they had high rates of atopic comorbidities like asthma, allergic rhinitis, and food allergies. Approximately one third of the patients had a prior systemic treatment for atopic dermatitis. Dupilumab dosing: q2w + TCS; weight-tiered: baseline weight 15 to<30 kg, 100 mg q2w + TCS, 200 mg loading dose; baseline weight ≥30 kg, 200 mg q2w + TCS, 400 mg loading dose. 300 mg q4w + TCS; 600 mg loading dose regardless of weight All patients received concomitant once-daily medium-potency TCS starting 2 weeks before baseline. Rescue treatment with high-potency TCS or systemic therapy was permitted. Of the study patients 362 (98.2%) received at least one dose of study treatment. 351 patients (95.6%) completed the study treatment.

Results

Table 3. Outcome 1: EASI-75 (number and proportion of patients achieving EASI-75)
Reference	Number of patients	Follow-up time (weeks)	Absolute number of events (%) I	Absolute number of events (%) C	Risk Ratio (95% CI) NNT (95% CI)
I= intervention; C=comparison; CI=confidence interval; RR=risk ratio, NNT=number needed to treat; q2w=dosing every two weeks; q4w=dosing every four weeks; TCS=topical corticosteroids
«Paller AS, Siegfried EC, Thaçi D ym. Efficacy and safety of dupilumab with concomitant topical corticosteroids in children 6 to 11 years old with severe atopic dermatitis: A randomized, double-blinded»1	Q2w+TCS n=122 placebo n=123	16	82 (67.2)	33 (26.8)	RR 2.51 (1.87-3.44) NNT 2.5 (1.9-3.4)
	Q4w+TCS n=122 placebo n=123	16	85 (69.7)	33 (26.8)	RR 2.6 (1.9-3.6), NNT 2.3 (1.85-3.2)
Level of evidence: moderate

Table 4. Outcome 2: IGA (Investigator's Global Assessment (IGA) score achieved 0/1 and reduction of ≥2 points from baseline)
Reference	Number of patients	Follow-up time (weeks)	Absolute number of events (%) I	Absolute number of events (%) C	Relative effect (RR)* (95% CI), NNT*
I= intervention; C=comparison; CI=confidence interval, RR=risk ratio, NNT=number needed to treat; *not reported, self-calculated; q2w=dosing every two weeks; q4w=dosing every four weeks; TCS=topical corticosteroids
«Paller AS, Siegfried EC, Thaçi D ym. Efficacy and safety of dupilumab with concomitant topical corticosteroids in children 6 to 11 years old with severe atopic dermatitis: A randomized, double-blinded»1	Q2w+TCS n=122 placebo n=123	16	36 (29.5)	14 (11.4)	RR 2.59 (1.47-4.56) NNT 5.5 (3.6-12.1)
	Q4w+TCS n=122 placebo n=123	16	40 (32.8)	14 (11.4)	RR 2.88 (1.65-5.02) NNT 4.7 (3.2-8.8)
Level of evidence: moderate

Table 5. Outcome 3: Pruritus (Proportion of patients with >4-point reduction in weekly average of daily Peak Pruritus NRS)
Reference	Number of studies and number of patients (I/C)	Follow-up time (weeks)	Absolute number of events (%) I	Absolute number of events (%) C	Relative effect (95% CI)
I=intervention; C=comparison; CI=confidence interval; NA=not available; q2w=dosing every two weeks; q4w=dosing every four weeks; TCS=topical corticosteroids
«Paller AS, Siegfried EC, Thaçi D ym. Efficacy and safety of dupilumab with concomitant topical corticosteroids in children 6 to 11 years old with severe atopic dermatitis: A randomized, double-blinded»1	Q2w+TCS n=122 placebo n=123	16	82 (67.2)	33 (26.8)	NA
	Q4w+TCS n=122 placebo n=123	16	85 (69.7)	33 (26.8)	NA
Level of evidence: low The level of evidence is downgraded due to imprecision.

References

Paller AS, Siegfried EC, Thaçi D ym. Efficacy and safety of dupilumab with concomitant topical corticosteroids in children 6 to 11 years old with severe atopic dermatitis: A randomized, double-blinded, placebo-controlled phase 3 trial. J Am Acad Dermatol 2020;83:1282-1293 «PMID: 32574587»PubMed