Week 24 results of a phase III trial in pediatric patients assessing secukinumab for the treatment of plaque psoriasis in children and young people

Psoriasis is a debilitating chronic skin condition, with plaque psoriasis representing the most common form in pediatric patients.¹ Despite well-established treatment guidelines for adult patients with psoriasis, treatment options in children are limited, and there are fewer clinical trials in the pediatric and adolescent population than in adults.¹

However, in October 2021, the National Institute for Health and Care Excellence (NICE) approved the use of the interleukin (IL)-17A monoclonal antibody secukinumab for the treatment of plaque psoriasis in children and young people aged 6–17 years.² The guidance recommends secukinumab for patients with moderate-to-severe disease, indicated by a Psoriasis Area and Severity Index (PASI) ≥10, and if the disease has failed to respond to, or the patient is not able to have, existing systemic therapies, including drugs such as ciclosporin and methotrexate, or phototherapy.

Here, we summarize the work of Magnolo et al.¹ who reported the 24-week outcomes from their phase III clinical trial of secukinumab in the treatment of pediatric patients with plaque psoriasis (NCT03668613). The study was published in the Journal of Academic Dermatology in January 2022.

Study design and patient characteristics

A phase III, multi-center, open-label, randomized clinical trial, was conducted across 23 sites around the world. A total of 92 patients were recruited, of whom 84 completed the screening phase. These patients were evenly randomized to high dose (HD) and low dose (LD) secukinumab groups. The study design can be seen in Figure 1 and baseline characteristics are detailed in Table 1.

D, day; CDLQI, Children’s Dermatology Quality of Life Index; IGA, Investigator Global Assessment; PASI, Psoriasis Area and Severity Index; SC, subcutaneous; W, week.

*Data from Magnolo, et al.^1
†Administered according to body weight: 75 mg for patients weighing <25 kg, 75 mg for patients weighing 25–49 kg, and 150 mg for patients weighing ≥50 kg.
^‡Administered according to body weight: 75 mg for patients weighing <25 kg, 150 mg for patients weighing 25–49 kg, and 300 mg for patients weighing ≥50 kg.
^§PASI-75/90/100 refers to the number of patients who have achieved a 75%/90%/100% reduction in their PASI score from baseline.

 

Table 1. Baseline characteristics of study participants*

HD, high dose; IGA, Investigator Global Assessment; LD, low dose; PASI, Psoriasis Area and Severity Index. *Adapted from Magnolo, et al.1
Characteristic, % (unless otherwise stated)	LD secukinumab (n = 42)	HD secukinumab (n = 42)
Age, years
6 to <12	40.5	38.1
12 to <18	59.5	61.9
Mean age, years (SD)	12.5 (2.39)	12.8 (3.42)
Female	47.6	59.5
Disease severity
Moderate	71.4	73.8
Severe	28.6	26.2
Baseline PASI
≤20	64.3	57.1
>20	35.7	42.9
Baseline IGA score
Grade 3 (moderate)	69.0	69.0
Grade 4 (severe)	31.0	31.0
Mean weight, kg (SD)	54.3 (19.7)	55.7 (19.3)
Weight, n (%)
<25 kg	4 (9.5)	4 (9.5)
25–49 kg	13 (31)	12 (28.6)
≥50 kg	25 (59.5)	26 (61.9)

Results

At 12 weeks, predictive log odds ratios (Table 2) suggest that treatment with secukinumab is superior for both the LD and HD groups relative to historical placebo. The estimated probability of a positive treatment effect with secukinumab was 100% when compared with placebo. In addition, both groups demonstrated good response rates in terms of PASI-75, PASI-90, and Investigator Global Assessment (IGA)-0/1 (Figure 2).

Table 2. Predictive log odds ratios of secukinumab at 12 weeks compared with a historical placebo*^†

HD, high dose; IGA, Investigator Global Assessment; LD, low dose; OR, odds ratio; PASI, Psoriasis Area and Severity Index. *Adapted from Magnolo, et al.1 †Using a non-responder imputation and the full analysis set.
Predictive log OR (95% credible interval)	LD secukinumab (n = 42)	HD secukinumab (n = 42)
PASI-75	4.9 (3.4–6.8)	4.8 (3.4–6.8)
PASI-90	4.4 (2.9–6.2)	4.7 (3.2–6.6)
IGA-0/1	4.3 (2.7–6.5)	4.4 (2.9–6.6)

Outcomes at Weeks A 12 and B 24 across the LD and HD secukinumab treatment groups.
HD, high dose; IGA, Investigator Global Assessment; LD, low dose; PASI, Psoriasis Area and Severity Index.
*Data from Magnolo, et al.¹

There were improvements in PASI, IGA-0/1, and Children’s Dermatology Quality of Life Index (CDQLI) scores from baseline at 12 weeks, and these improvements continued at 24 week (Table 3). One patient in the HD group discontinued treatment due to a lack of efficacy.

Table 3. PASI, IGA, and CDLQI score response rates at Weeks 12 and 24 for the LD and HD secukinumab treatment groups*

CDLQI, Children’s Dermatology Quality of Life Index; HD, high dose; IGA, Investigator Global Assessment; LD, low dose; PASI, Psoriasis Area and Severity Index. *Data from Magnolo, et al.1
Score, % (unless otherwise stated)	LD secukinumab (n = 42)	HD secukinumab (n = 42)
Improvement from mean baseline PASI at 12 weeks	92.6	93.9
Improvement from mean baseline PASI at 24 weeks	96.4	96.6
Mean baseline CDQLI, score (SD)	10.6 (6.0)	13.0 (7.0)
Week 12 mean CDQLI, score	2.1	2.2
Week 12 improvement from baseline CDQLI	78.4	83.3
Week 24 mean CDQLI, score	1.5	2.0
Week 24 improvement from baseline CDQLI	88.1	92.9
Week 12 mean CDQLI decrease from baseline	78.4	83.3
Week 24 mean CDQLI decrease from baseline	86	80.6
Week 12 CDQLI of 0/1	50.0	61.9
Week 24 CDQLI of 0/1	70.7	60.5

Secukinumab was generally well tolerated, with a similar safety profile to that seen in the phase III trials performed in adults. The most common adverse events by system organ class were infections and infestations, with nasopharyngitis and acne the most common by preferred term (Table 4). Two patients in the HD group discontinued treatment due to adverse events and there were no treatment-related deaths. Of note, Candida infections were less frequent (1.2%) in the pediatric population compared with studies in adults (2.3–4.7%).³

Table 4. Adverse events*

AE, adverse event; HD, high dose; LD, low dose; TEAE, treatment-emergent adverse event. *Adapted from Magnolo, et al.1
AE, % (unless otherwise stated)	LD secukinumab (n = 42)	HD secukinumab (n = 42)
Any TEAE	57.1	57.1
Most common AE by system organ class
Infections and infestations	35.7	42.9
Gastrointestinal disorders	9.5	19.0
Skin/subcutaneous disorders	9.5	9.5
Most common AE by preferred term
Nasopharyngitis	14.3	9.5
Acne	7.1	2.4
Diarrhea	0.0	7.1
Leukopenia	4.8	2.4
Neutropenia	4.8	2.4
Pyrexia	7.1	0.0
Upper respiratory tract infection	0.0	7.1

Conclusion

Overall, the 24 week analysis demonstrates that secukinumab is well tolerated in pediatric patients with plaque psoriasis and is efficacious at achieving a clinical response and improving quality of life in this population. The study is ongoing and aims to assess long-term efficacy and safety over a 4-year period. The main limitations of the trial are it’s open-label nature and the lack of a placebo or control group.