Long-term safety and efficacy of secukinumab in pediatric patients with plaque psoriasis

Plaque psoriasis affects up to 2.1% of children and adolescents; however, there are a limited number of available treatments in this population compared with adults.¹ The manifestation of psoriasis in pediatric patients can be different to adults, with many patients affected by comorbidities, including diabetes, obesity, and Crohn’s disease.¹

In addition to the lack of approved topical and systemic treatments for pediatric patients, there are limited data on the long-term efficacy and safety of treatments.¹ The Psoriasis and Psoriatic Arthritis Hub has previously reported on the 24-week results of a phase III trial of secukinumab, an anti-interleukin-17A monoclonal antibody in pediatric patients with plaque psoriasis. Long-term data are necessary to evaluate the impact of disease and subsequent treatment on a patient’s quality of life. Here, we discuss the results of long-term study of secukinumab, up to 104 weeks, in children and adolescents.

Study design

In this study (NCT02471144), 162 patients were randomized 1:1:1:1 to either low dose or high-dose secukinumab, etanercept, or placebo.¹ Patients who were randomized to secukinumab received a dose based on their body weight in both dosing groups.¹ The primary endpoint of the trial was the proportion of patients treated with secukinumab achieving a 75% improvement in Psoriasis Area and Severity Index (PASI 75) and/or a Investigator’s Global Assessment (IGA) modified 2011 score of 0 or 1 at Week 12.² The study design is shown in Figure 1.

Patients entered a 16-week treatment-free follow-up if they:

• discontinued treatment;
• were etanercept-treated patients who completed with Week 52;
• were placebo-treated patients who achieved PASI 75 at Week 12; or
• were secukinumab-treated patients who completed the extension.²

A total of 155 of the 162 randomized patients were included in the interim analysis.¹

Figure 1. Study design* 

BSA, body surface area; EoM, end of maintenance; EoT, end of trial; IGA Mod 2011, Investigator’s Global Assessment modified 2011; PASI, Psoriasis Area and Severity Index.
*Adapted from Krasowska, et al.¹ and Bodemer, et al.²

Results

Patient characteristics at baseline are shown in Table 1. Most patients were female, White, and aged ≥12 years, with a mean PASI score of 28.0 ± 0.4.²

Table 1. Baseline patient characteristics*

Safety¹

The safety data for secukinumab-treated patients were assessed to Week 104, with no deaths reported across the whole study. The most common adverse events (AEs) across all treatment groups were infections and infestations (by system organ class) as shown in Figure 2. The rate of AEs and serious AEs did not increase with secukinumab treatment on a year-by-year basis.

Figure 2. Incidence of TEAEs and infections and infestations* 

EAIR, exposure adjusted incidence rate; TEAE, treatment-emergent adverse event.
*Adapted from Krasowska, et al.¹

Pubertal development was also measured during the study using Tanner stage scores. Scores increased throughout the study and the use of secukinumab did not appear to negatively impact the pubertal development of patients.

Efficacy¹

Efficacy responses in both the high and low-dose secukinumab groups were sustained from Week 52 to Week 104. IGA 0/1 and PASI 75/100 responses at Weeks 52 and Week 104 are shown in Figure 3. The percentage of patients achieving PASI 100 at Week 104 was higher in patients receiving higher doses of secukinumab compared with lower doses. The mean PASI score at Week 104 was also lower in the high-dose secukinumab group (1.30) compared with the lower-dose group (2.51).

Figure 3. IGA 0/1, PASI 75, and PASI 100 responses* 

HD, high dose; IGA Mod 2011, Investigator’s Global Assessment modified 2011; LD, low dose; PASI 75, 75% improvement in Psoriasis Area and Severity Index; PASI 100, 100% improvement in Psoriasis Area and Severity Index.
*Adapted from Krasowska, et al.¹

In patients treated with low-dose secukinumab, the mean Children’s Dermatology Life Quality Index (CDLQI) score change from baseline was −9.6 at Week 52, but the change reduced by Week 104 (−8). In patients treated with high-dose secukinumab, the mean CDLQI score change from baseline remained stable, from −9 at Week 52 to −8.9 at Week 104.

This study is limited by the sample size involved and the lack of statistical analysis between the secukinumab treatment groups, meaning it is difficult to determine if there are any statistically significant differences between the groups.¹ However, the data provided from this study highlight the potential of secukinumab in pediatric patients with plaque psoriasis.

Conclusion

This long-term, phase III study has demonstrated that secukinumab demonstrated an acceptable safety profile in pediatric patients, with sustained efficacy up to 104 weeks. Improvements in PASI scores were maintained from Week 52 to Week 104. In addition, patients treated with secukinumab experienced an improvement in their quality of life, as demonstrated by an increase in the number of patients who achieved CDLQI 0/1 at Week 104. During the study, the majority of AEs were mild or moderate, with no new safety signals.