Abstract
Background:
Secukinumab, an IL-17A inhibitor, is approved for moderate to severe psoriasis in children over 6 years old in the European Union and the United States, but not yet in China. This study evaluates the clinical efficacy and safety of secukinumab in Chinese pediatric patients with moderate to severe plaque psoriasis.
Methods:
A randomized, single-center study was conducted with 33 patients aged 6 to 17 years. Patients were treated with either secukinumab or conventional non-biologic therapy. The primary outcomes assessed included body surface area (BSA), Psoriasis Area and Severity Index (PASI) 75/90/100 responses, Investigator’s Global Assessment 0/1 (IGA 0/1), Dermatology Life Quality Index, and the incidence of adverse events (AEs).
Results:
Compared to the conventional treatment group, the secukinumab group demonstrated significant reductions in BSA and PASI scores, as well as higher rates of IGA 0/1, Dermatology Life Quality Index improvement, and PASI 90 response. Subgroup analysis of the secukinumab group indicated lower BSA and PASI scores in patients without prior treatment compared to those with prior treatment. No significant differences were observed between the 150 mg and 300 mg dose groups regarding BSA and PASI decrease rates.
Conclusion:
Secukinumab demonstrates therapeutic efficacy and safety in the treatment of moderate to severe plaque psoriasis in pediatric and adolescent patients, suggesting its potential as a treatment option for this population.
Keywords: biologic therapy, pediatric, psoriasis, secukinumab
1. Introduction
Psoriasis is a chronic epidermal hyperplastic and inflammatory skin disease characterized by well-defined erythematous plaques covered with silvery-white scales. It is caused by the interaction of various inflammatory cells and cytokines in susceptible individuals, and the Th17/IL-23 axis plays a key role in the disease development.[1–3] Pediatric psoriasis represents a distinct group with a global prevalence of 0% to 1.37%, one-third of which onset during childhood. Kelly reported a 30.5% reduction in health-related quality of life among children aged 5 to 16 years with psoriasis. Several studies have indicated a linear increase in psoriasis incidence among the children population,[4,5] which seriously affects sleep, social interactions, learning, and psychological well-beings.[6] The psychological impact of the unpredictability of the disease process contributes to treatment frustration and dissatisfaction. Parents or caregivers of children with psoriasis often suffer from anxiety, guilt and depression, which reduces their quality of life and affects family relationship.[7] Plaque psoriasis is the most common clinical subtype of psoriasis in children,[8] but due to the unique characteristics of children, there is a scarcity of clinical trial data on the efficacy and safety of systemic drug therapies for children with psoriasis, and a lack of international and domestic standardized treatment guidelines.[9] The number of drugs approved for systemic treatment is relatively limited, posing diagnostic and therapeutic challenges. Tumor necrosis factor-α (TNF-α), interleukin (IL)-12/23, and IL-17 are known cytokines involved in the pathogenesis of psoriasis. According to the mechanism of these various cytokines, the therapeutic landscape for pediatric psoriasis has expanded in recent years. Biological agents such as TNF-α inhibitors (infliximab, adalimumab and etanercept), IL-12/23 inhibitor (ustekinumab) and IL-17A inhibitor (secukinumab) have been successfully applied in the treatment for adults, but the efficacy of biological agents in children with moderate to severe plaque psoriasis in Chinese children is unknown.
Secukinumab is a high-affinity humanized IgG1 monoclonal antibody, which selectively binds to the proinflammatory cytokine IL-17A and inhibits the release of proinflammatory cytokines and chemokines.[10] Secukinumab has been approved by the European Commission and the United States for the treatment of moderate to severe plaque psoriasis in patients aged 6 years or above, who are eligible for systemic therapy. However, compared to its use in adults, there are only a few reports on the application of secukinumab in children with moderate to severe plaque psoriasis,[11–14] necessitating further clinical exploration. Our study aimed to explore the efficacy of secukinumab in children with moderate to severe plaque psoriasis in Chinese children.
2. Materials and methods
2.1. Study design
This study was conducted from July 2020 to September 2022 in the National Clinical Research Center for Skin and Immune Diseases (Peking University First Hospital) with approval from Peking University First Hospital Biomedical Research Ethics Committee. Informed consent was obtained from participants (or their parents/legal guardians/next of kin). Patients aged 6 to < 18 years diagnosed with moderate to severe plaque psoriasis were divided into secukinumab group and conventional non-biologic treatment group (conventional group). Within the secukinumab group, patients were further divided into 2 subgroups based on whether they received traditional systemic therapies before initiating biological agent treatment. We evaluated the body surface area (BSA), Psoriasis Area and Severity Index (PASI) 75/90/100 response rates, Investigator’s Global Assessment revision 2011 0/1 (IGA 0/1), Dermatology Life Quality Index (DLQI), and adverse events (AEs) after 4 and 8 weeks treatment.
2.2. Inclusion and exclusion criteria
Pediatric patients enrolled were aged 6 to < 18 years who met the diagnostic criteria of moderate to severe for plaque psoriasis, generally characterized by a BSA > 10% or PASI > 10. These patients were screened for the absence of tuberculosis, HBV infection, malignancies or severe underlying medical conditions.
2.3. Intervention
Patients were randomly assigned to receive subcutaneous injection of secukinumab (Cosentyx, Novartis Pharmaceuticals, Switzerland) at 0, 1, 2, 3, 4, and 8 weeks, with doses of either 300 mg or 150 mg. The conventional non-biologic treatment group includes oral methotrexate/cyclosporin/acitretin/traditional Chinese medicine, the dosage of non-biologic therapy is based on the instructions of the respective medication.
2.4. Efficacy evaluation
PASI, BSA, IGA, DLQI, and AEs were evaluated at 4 and 8 weeks after treatment. The PASI improvement rate = (total score before treatment − total score after treatment)/total score before treatment × 100%. PASI 75, PASI 90, and PASI 100 represented the achievement of improvement rates of 75%, 90%, and 100% of the total score, respectively.
2.5. Statistical methods
The measurement data were presented as mean ± standard deviation. The differences between groups were calculated with t-test, Fisher exact test, Wilcoxon test or chi-square test accordingly. Statistical analysis was performed using GraphPad Prism 8 software. P-value < .05 was considered statistically significant. * was used to denote significance levels in the figures as follows: *P < .05; **P < .01; ***P < .001; ****P < .0001.
3. Results
3.1. Baseline characters
A total of 33 patients were included in this study (Fig. 1). They were divided into secukinumab treatment group (N = 24) and conventional non-biologic treatment group (N = 9). The secukinumab group were further divided into 2 groups based on whether traditional systemic therapies were used before. Fifteen of them had no prior experience while the remaining 9 patients had. In both secukinumab with and without pre-traditional systemic treatment experience subgroups, 3 patients in each subgroup were assigned a dosage of 150 mg, and the rest received 300 mg. The demographics and baseline characteristic data were balanced and comparable between both groups (Table 1). Overall, 51.52% of the patients were male, with the mean age, weight, height, and body mass index being 13.52 years, 48.70 kg, 149.21 cm and 20.79 kg/m2, respectively. The mean baseline PASI score was 19.71, the mean baseline total BSA involvement was 36.17%, and the mean DLQI score was 9.39 in overall population. The baseline IGA score was classified as moderate (2/3) in 67% patients and severe (4) in 33% patients. There were no differences in age, gender, weight, height, body mass index, and severity of skin lesions among the groups (P > .05).
Figure 1.
Patient disposition.
Table 1.
Demographic and baseline disease characteristics.
| SEC group (N = 24) | SEC subgroup: without pre-traditional treatments (N = 15) | SEC subgroup: with pre-traditional treatments (N = 9) | P | ||
|---|---|---|---|---|---|
| Age (yr), mean ± SD | 13.42 ± 3.19 | 13.20 ± 3.32 | 13.78 ± 3.11 | .86 | |
| Sex, n (%) | |||||
| Male | 13 (52%) | 8 (53%) | 5 (56%) | .88 | |
| Female | 11 (48%) | 7 (47%) | 4 (44%) | ||
| Weight (kg), mean ± SD | 50.13 ± 25.68 | 47.73 ± 21.50 | 54.11 ± 32.54 | .70 | |
| Height (cm), mean ± SD | 150.25 ± 19.47 | 149.47 ± 19.47 | 151.56 ± 20.59 | .85 | |
| BMI (kg/m²), mean ± SD | 20.96 ± 7.41 | 20.48 ± 6.49 | 21.76 ± 9.11 | 0.89 | |
| Baseline total BSA, mean ± SD | 35.65 ± 26.25 | 32.97 ± 24.86 | 40.11 ± 29.40 | .67 | |
| Baseline PASI, mean ± SD | 21.40 ± 10.83 | 20.49 ± 8.89 | 22.93 ± 13.96 | .09 | |
| Baseline IGA score, n (%) | |||||
| 2/3 = moderate | 14 (58.33%) | 9 (60%) | 5 (55.56%) | .25 | |
| 4 = severe | 10 (41.67%) | 6 (40%) | 4 (44.44%) | ||
| DLQI score, mean ± SD | 10.33 ± 6.94 | 10.33 ± 7.51 | 10.33 ± 6.32 | .48 | |
| SEC subgroup: without pre-traditional treatments (N = 15) | SEC subgroup: with pre-traditional treatments (N = 9) | P | |||
|---|---|---|---|---|---|
| Age (yr), mean ± SD | 13.20 ± 3.32 | 13.78 ± 3.11 | .68 | ||
| Sex, n (%) | |||||
| Male | 8 (53%) | 5 (56%) | 1.00 | ||
| Female | 7 (47%) | 4 (44%) | |||
| Weight (kg), mean ± SD | 47.73 ± 21.50 | 54.11 ± 32.54 | .57 | ||
| Height (cm), mean ± SD | 149.47 ± 19.47 | 151.56 ± 20.59 | .81 | ||
| BMI (kg/m²), mean ± SD | 20.48 ± 6.49 | 21.76 ± 9.11 | 1.00 | ||
| Baseline total BSA, mean ± SD | 32.97 ± 24.86 | 40.11 ± 29.40 | .53 | ||
| Baseline PASI, mean ± SD | 20.49 ± 8.89 | 22.93 ± 13.96 | .91 | ||
| Baseline IGA score, n (%) | |||||
| 2/3 = moderate | 9 (60%) | 5 (55.56%) | 1.00 | ||
| 4 = severe | 6 (40%) | 4 (44.44%s) | |||
| DLQI score, mean ± SD | 10.33 ± 7.51 | 10.33 ± 6.32 | 1.00 | ||
| SEC group (N = 24) |
Conventional non-biologic treatments group (N = 9) | P | |||
|---|---|---|---|---|---|
| Age (yr), mean ± SD | 13.42 ± 3.19 | 13.78 ± 2.22 | .95 | ||
| Sex, n (%) | |||||
| Male | 13 (52%) | 4 (44%) | .71 | ||
| Female | 11 (48%) | 5 (56%) | |||
| Weight (kg), mean ± SD | 50.13 ± 25.68 | 44.89 ± 16.43 | .82 | ||
| Height (cm), mean ± SD | 150.25 ± 19.47 | 146.44 ± 15.61 | .60 | ||
| BMI (kg/m²), mean ± SD | 20.96 ± 7.41 | 20.34 ± 4.41 | .63 | ||
| Baseline total BSA, mean ± SD | 35.65 ± 26.25 | 37.56 ± 27.34 | .69 | ||
| Baseline PASI, mean ± SD | 21.40 ± 10.83 | 15.18 ± 16.06 | .03 | ||
| logPASI | 2.95 ± 0.48 | 2.34 ± 0.89 | .08 | ||
| Baseline IGA score, n (%) | |||||
| 2/3 = moderate | 14 (58.33%) | 8 (88.89%) | .21 | ||
| 4 = severe | 10 (41.67%) | 1 (11.11%) | |||
| DLQI score, mean ± SD | 10.33 ± 6.94 | 6.89 ± 7.57 | .23 | ||
P values were calculated with t-test, Fisher exact test, Wilcoxon test or chi-square test.
BMI = body mass index, BSA = body surface area, DLQI = Dermatology Life Quality Index, IGA = Investigator’s Global Assessment, PASI = psoriasis area and severity index, SD = standard deviation, SEC = secukinumab.
3.2. Efficacy: BSA and PASI changes
The results of BSA score, BSA decrease rate, PASI scores and PASI decrease rate data in different groups were summarized in Table 2. The BSA of patients in the conventional non-biologic treatment group and secukinumab group (overall, without and with pre-traditional treatment) was lower at week 4 and 8 than that in their respective groups at week 0 (Fig. 2a). The BSA of the secukinumab group was lower than that of the conventional group (P < .05), and the BSA of the secukinumab without pre-traditional treatment group was lower than that of both the conventional and secukinumab with pre-traditional treatment group (P < .01 and P < .05) at week 4. The BSA of the secukinumab group and the subgroup without pre-traditional treatment were lower than that of the conventional non-biologic group at week 8 (P < .01). The BSA score of the secukinumab without pre-traditional treatment group was also lower than that of the subgroup with pre-traditional treatment (P < .01).
Table 2.
BSA score, BSA decrease rate, PASI scores, and PASI decrease rate in different groups.
| 4w CON | 4w SEC | 4w SEC wo tra | 4w SEC w tra | 8w CON | 8w SEC | 8w SEC wo tra | 8w SEC w tra | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Total | 150 mg | 300 mg | Total | 150 mg | 300 mg | Total | 150 mg | 300 mg | Total | 150 mg | 300 mg | |||||
| BSA | 15.10 ± 13.90 | 8.60 ± 18.20 | 2.90 ± 3.00 | 18.10 ± 27.70 | 18.90 ± 30.00 | 3.00 ± 8.20 | 0.90 ± 1.30 | 6.60 ± 12.90 | ||||||||
| P (BSA vs baseline) | 4.83e-2* | 1.06e-07**** | 2.37e-05**** | 3.62e-3** | 8.45e-3** | 2.25e-13**** | 3.96e-08**** | 6.00e-06**** | ||||||||
| P (BSA 4w vs 8w) | - | - | - | - | 1.00 | 8.48e-4*** | 0.06 | 0.01* | ||||||||
| P (BSA vs CON) | - | 0.03* | 5.40e-3** | 0.48 | - | 4.62e-3** | 1.17e-3** | 0.18 | ||||||||
| 0.03*(w-tra vs wo-tra) | 8.69e-3**(w-tra vs wo-tra) | |||||||||||||||
| PASI | 4.50 ± 4.20 | 3.50 ± 4.30 | 1.70 ± 1.60 | 6.50 ± 5.70 | 8.50 ± 16.60 | 0.90 ± 1.40 | 0.70 ± 1.50 | 1.20 ± 1.10 | ||||||||
| P (PASI vs baseline) | 0.11 | 3.49e-07**** | 4.95e-05**** | 5.91e-3** | 5.27e-3** | 1.91e-13**** | 1.32e-08**** | 2.27e-05**** | ||||||||
| P (PASI 4w vs 8w) | - | - | - | - | 0.49 | 2.43e-4*** | 1.13e-2* | 0.04* | ||||||||
| P (PASI vs CON) | - | 0.24 | 0.03* | 0.57 | - | 6.77e-3** | 1.40e-3** | 0.23 | ||||||||
| 0.03*(w-tra vs wo-tra) | 0.04*(w-tra vs wo-tra) | |||||||||||||||
| BSA decrease rate | 49.50 ± 39.90 | 69.40 ± 32.10 | 74.60 ± 30.80 | 92.30 ± 6.70 | 70.20 ± 33.00 | 60.70 ± 34.30 | 63.20 ± 28.40 | 59.40 ± 39.40 | 60.20 ± 33.00 | 91.20 ± 12.50 | 94.10 ± 9.30 | 99.50 ± 0.80 | 92.80 ± 10.00 | 86.40 ± 16.00 | 85.40 ± 16.30 | 86.80 ± 17.40 |
| P (BSA d-rate 4w vs 8w) | - | - | - | - | - | - | - | - | 0.43 | 0.00**** | 7.00e-3** | 0.25 | 0.03* | 1.4e-2* | 0.27 | 3.6e-2* |
| P (vs CON) | - | 0.15 | 0.10 | 1 (150 vs 300 mg) | 0.53 | 0.80 (150 vs 300 mg) | - | 5.13e-3** | 2.18e-3** | 0.18 (150 vs 300 mg) | 0.11 | 0.60 (150 vs 300 mg) | ||||
| 0.12 (w-tra vs wo-tra) | 0.02*(w-tra vs wo-tra) | |||||||||||||||
| PASI decrease rate | 47.74 ± 51.96 | 83.61 ± 19.68 | 91.70 ± 6.82 | 94.37 ± 1.82 | 90.95 ± 7.49 | 70.13 ± 26.55 | 69.85 ± 33.27 | 70.27 ± 26.18 | 56.16 ± 47.62 | 95.27 ± 7.41 | 96.84 ± 5.73 | 99.53 ± 0.82 | 96.16 ± 6.26 | 92.66 ± 9.40 | 92.70 ± 0.95 | 92.65 ± 11.87 |
| P (PASI d-rate 4w vs 8w) | - | - | - | - | - | - | - | - | 0.43 | 0.00**** | 7.00e-3** | 0.25 | 0.03* | 1.4e-2* | 0.27 | 3.6e-2* |
| P (vs CON) | - | 0.15 | 0.10 | 1 (150 vs 300 mg) | 0.53 | 0.80 (150 vs 300 mg) | - | 5.13e-3** | 2.18e-3** | 0.18 (150 vs 300 mg) | 0.11 | 0.60 (150 vs 300 mg) | ||||
| 0.12 (w-tra vs wo-tra) | 0.02*(w-tra vs wo-tra) | |||||||||||||||
*P < .05.
**P < .01.
***P < .001.
****P < .0001.
BSA = body surface area, CON = conventional non-biologic treatment group, PASI = Psoriasis Area and Severity Index, SEC w tra = secukinumab with traditional treatment group, SEC wo tra = secukinumab without traditional treatment group, SEC = secukinumab group.
Figure 2.
BSA, BSA decrease rate, PASI and PASI decrease rate in each group. *: P < .05; **: P < .01; ***: P < .001; ****: P < .0001. con = conventional non-biologic treatment group, SEC = secukinumab group, SEC wo tra = secukinumab without pre-traditional treatment group, SEC w tra = secukinumab with pre-traditional treatment group, BSA = body surface area, PASI = Psoriasis Area and Severity Index.
For the BSA decrease rate, we compared the intra-group and inter-group differences at week 4 and 8 (Fig. 2b). In terms of the inter-group differences, the secukinumab, secukinumab without pre-traditional treatment, 300 mg secukinumab without pre-traditional treatment, 300 mg secukinumab with pre-traditional treatment all showed increases at week 8 compared to their respective week 4 groups (P < .0001, P < .01, P < .05, P < .05, respectively). As for the intra-group differences, the BSA decrease rates of the secukinumab group and the subgroup without pre-traditional treatment were higher than that of conventional non-biologic treatment group (P < .01). The analysis of the secukinumab subgroup showed that the BSA decrease rate in the subgroup without pre-traditional treatment was higher compared to the subgroup with pre-traditional treatment (P < .05). There were no differences between the groups receiving secukinumab with 150 mg and 300 mg dosage at both week 4 and 8 (P < .05).
In Figure 2c, the PASI scores of secukinumab group, secukinumab without and with pre-traditional treatment were lower than their respective week 0 groups at both 4 and 8 weeks. Only the conventional non-biologic treatment group at week 8 showed a decrease compared with week 0 (P < .01). The PASI scores of the secukinumab group, secukinumab without pre-traditional group and secukinumab with pre-traditional group at week 8 were lower than those at week 4 (P < .001, P < .05, P < .05, respectively). For the intra-group comparisons, we used the logPASI (normal distribution transformation) value to evaluate the differences between the secukinumab and conventional group. At week 4, the secukinumab without pre-traditional treatment group showed a reduction compared to both the conventional and secukinumab with pre-traditional treatment group (P < .05). At week 8, the logPASI value of secukinumab group showed lower score than that of the conventional non-biologic treatment group (P < .01). The PASI score in secukinumab without pre-traditional treatment group also showed decrease compared to the conventional group and secukinumab with pre-traditional treatment group (P < .01 and P < .05, respectively). The improvement rate of PASI, shown in Figure 2d, displayed differences between each group. The secukinumab, secukinumab without pre-traditional treatment (total and 300 mg dose), secukinumab with pre-traditional treatment group (total and 300 mg dose) exhibited increase at week 8 compared to week 4 (P < .0001, P < .01, P < .05, P < .05, P < .05, respectively). For the intra-group of week 4 treatment, there were no differences between each group. After 8 weeks treatment, the PASI improvement rates of the intra-group results showed that both the secukinumab and secukinumab without pre-traditional treatment had higher improvement rates than conventional non-biologic treatment group (P < .01). Furthermore, the PASI improvement rate of the secukinumab without pre-traditional treatment group was also higher than that of the secukinumab with pre-traditional treatment group (P < .05). Like the BSA decrease rate results, there were no differences between 150 and 300mg doses at both week 4 and 8 (P > .05).
3.3. Efficacy: response rates (IGA, DLQI, PASI)
The number of responses rates of IGA, DLQI and PASI in patients between different groups are shown in Table 3, therapeutic efficacy of secukinumab was evaluated at week 4 and 8 of treatment (Fig. 3). In Figure 4a, at week 4 and 8, secukinumab group patients generally had higher PASI 75, 90, 100 rates than the conventional non-biologic treatment group. At week 4, the rate of PASI 75 responders in the secukinumab without pre-traditional treatment group were higher than the conventional non-biologic treatment and secukinumab with pre-traditional treatment group (P < .05). For the PASI 75 at week 8 and PASI 90 at week 4, both the secukinumab and secukinumab without pre-traditional treatment groups were higher than the conventional group (P < .05). Differences were observed only in the PASI 90 response rates between all secukinumab groups and the conventional non-biologic treatment group at week 8. The secukinumab without pre-traditional treatment group had generally higher rates than secukinumab with pre-traditional treatment group, while only PASI 75 at week 4 showed difference between 2 subgroups (P < .05).
Table 3.
Results of IGA, DLQI, and PASI responses of patients between different groups according to weeks.
| CON (N = 9) | SEC (N = 24) | SEC wo tra (N = 15) | SEC w tra (N = 9) | |
|---|---|---|---|---|
| PASI 75, n (%) | ||||
| W4 | 5 (60.00) | 20 (80.00) | 15 (100.00) | 5 (60.00) |
| W8 | 5 (60.00) | 23 (95.83) | 15 (100.00) | 8 (88.89) |
| PASI 90, n (%) | ||||
| W4 | 1 (11.11) | 14 (58.33) | 11 (73.33) | 3 (33.33) |
| W8 | 3 (33.33) | 22 (91.67) | 14 (93.33) | 8 (88.89) |
| PASI 100, n (%) | ||||
| W4 | 0 (0.00) | 2 (8.33) | 2 (13.33) | 0 (0.00) |
| W8 | 0 (0.00) | 7 (29.17) | 6 (40.00) | 1 (11.11) |
| IGA 0/1, n (%) | ||||
| W4 | 2 (22.22) | 11 (45.83) | 7 (46.67) | 4 (44.44) |
| W8 | 3 (33.33) | 21 (87.50) | 14 (93.33) | 7 (77.78) |
| DLQI 0/1, n (%) | ||||
| W4 | 2 (22.22) | 13 (54.17) | 10 (66.67) | 3 (33.33) |
| W8 | 2 (22.22) | 16 (66.67) | 11 (73.33) | 5 (55.55) |
CON = conventional non-biologic treatment group, DLQI = Dermatology Life Quality Index, IGA = Investigator’s Global Assessment revision 2011, PASI = Psoriasis Area and Severity Index, SEC w tra = secukinumab with traditional treatment group, SEC wo tra = secukinumab without traditional treatment group, SEC = secukinumab group, W = week.
Figure 3.
IGA 0/1 and PASI 75/90/100 responses at 4 and 8 weeks. CON = conventional non-biologic treatment group, SEC = secukinumab group; SEC without traditional: secukinumab without pre-traditional treatment group; SEC with traditional: secukinumab with pre-traditional treatment group. IGA = Investigator’s Global Assessment, PASI = Psoriasis Area and Severity Index.
Figure 4.
IGA 0/1, DLQI 0/1, PASI 75/90/100 responses at 4 and 8 weeks. *P < .05; **P < .01; ***P < .001; ****P < .0001. CON: conventional non-biologic treatment group; SEC: secukinumab group; SEC without traditional: secukinumab without pre-traditional treatment group; SEC with traditional: secukinumab with pre-traditional treatment group. DLQI = Dermatology Life Quality Index, IGA = Investigator’s Global Assessment, PASI = Psoriasis Area and Severity Index.
The IGA 0/1 response rates at week 4 and 8 (Fig. 3) indicated that the secukinumab group and secukinumab without pre-traditional treatment group were higher than the conventional group at week 8 (Fig. 4b) (P < .01). At week 4, the proportion of patients with IGA 0/1 was higher in the secukinumab (45.83%) than the conventional non-biologic treatment groups (22.22%), but it was similar in the secukinumab without pre-traditional treatment (46.67%) and secukinumab with pre-traditional treatment groups (44.44%). At week 8, the secukinumab group (87.5%) and secukinumab without pre-traditional treatment group (93.33%) had much higher rates than conventional group (33.33%). There were no differences between the secukinumab without pre-traditional treatment and secukinumab with pre-traditional treatment group. In addition, the IGA 0/1 response rates of both secukinumab group and secukinumab without pre-traditional treatment group at week 8 were higher than their corresponding group at week 4 (P < .01 and P < .05).
For the patients achieving the DLQI score of 0/1, we also found only secukinumab and secukinumab without pre-traditional treatment group had higher rates than the conventional group at week 8 (Fig. 4c) (P < .05). At week 4, the proportion of patients achieving the DLQI score of 0/1 was higher in secukinumab group (54.17%) than in conventional non-biologic treatment group (22.22%), and the secukinumab without pre-traditional treatment group(66.67%) was higher than secukinumab with pre-traditional treatment group (33.33%). At week 8, the percentage of the DLQI score of 0/1 in the secukinumab group (66.67%) and secukinumab without pre-traditional treatment group (73.33%) were higher than in the conventional group (22.22%). The secukinumab without pre-traditional treatment group (73.33%) and secukinumab with pre-traditional treatment (55.55%) group showed no difference.
3.4. Safety
In terms of safety, adverse events were evaluated including bacteria, tuberculosis, viral hepatitis virus, fungus, blood and lymphatic system diseases, nervous system diseases, cardiovascular disorders, respiratory or thoracic and mediastinal diseases, gastrointestinal diseases, allergic or other skin and subcutaneous tissue diseases, malignant tumors, and others. During the treatment and follow-up period, no patients experienced infections, malignant tumors, allergies, or serious adverse reactions. Detailed information about safety profile were listed in Table 4.
Table 4.
Overall safety profile.
| Patients with AEs, n (%) | CON (N = 9) | SEC wo tra (N = 15) | SEC w tra (N = 9) |
|---|---|---|---|
| Total | 0 (0%) | 0 (0%) | 0 (0%) |
| Infection and infestation: bacteria | 0 (0%) | 0 (0%) | 0 (0%) |
| Infection and infestation: tuberculosis | 0 (0%) | 0 (0%) | 0 (0%) |
| Infection and infestation: viral hepatitis virus | 0 (0%) | 0 (0%) | 0 (0%) |
| Fungus | 0 (0%) | 0 (0%) | 0 (0%) |
| Blood and lymphatic system diseases | 0 (0%) | 0 (0%) | 0 (0%) |
| Nervous system diseases | 0 (0%) | 0 (0%) | 0 (0%) |
| Cardiovascular disorders | 0 (0%) | 0 (0%) | 0 (0%) |
| Respiratory or thoracic and mediastinal diseases | 0 (0%) | 0 (0%) | 0 (0%) |
| Gastrointestinal diseases | 0 (0%) | 0 (0%) | 0 (0%) |
| Allergic or other skin and subcutaneous tissue diseases | 0 (0%) | 0 (0%) | 0 (0%) |
| Malignant tumors | 0 (0%) | 0 (0%) | 0 (0%) |
| Others | 0 (0%) | 0 (0%) | 0 (0%) |
AE = adverse events, CON = conventional non-biologic treatment group, SEC w tra = secukinumab with traditional treatment group, SEC wo tra = secukinumab without traditional treatment group, SEC = secukinumab group.
4. Discussion
Secukinumab was approved by the European Medicines Agency in 2020 and the U.S. Food and Drug Administration in 2021 for the treatment of moderate to severe plaque psoriasis in patients aged 6 years or older. In the “Expert Consensus on the Diagnosis and Treatment of Pediatric Psoriasis” published by the Pediatric Group of the Dermatology and STD Branch of the Chinese Medical Association in 2021, it also pointed out that secukinumab was effective and safe in the treatment of plaque psoriasis in children with fewer emergency adverse events. Our research design is reasonable and its effectiveness is also consistent with international research. Recent studies suggest that biological agents are more effective and safer than traditional nonspecific immunosuppressants in the treatment of pediatric psoriasis.[15] Although biological agents have been successfully used in the treatment of psoriasis in adults,[16,17] there is still limited research in children. The youngest reported case was a 3-month-old Filipino girl with excellent response to secukinumab,[18] further confirming its safety and reliability.
Generally, the dosage of secukinumab used for pediatric patients depends on their weight (75 mg for < 25 kg and 25 to < 50 kg; 150 mg/300 mg for≥ 50 kg), some patients may even benefit from higher doses. In our study, with the consent of the patients’ families, we took 300 mg for the treatment of psoriasis in children, and 3 patients in each secukinumab subgroup were randomly selected to receive 150 mg treatment. According to results of the BSA and PASI decrease rates between each intra-group in Figure 2b and 2d, there was no difference between 150 and 300 mg doses.
Compared to these internationally well-known 24 to 52 week randomized, double-blind, multicenter studies,[11,12,19] our study only involved 33 patients with a maximum follow-up of 8 weeks. The reason is that the number of patients who can complete the follow-up was limited, and many parents in China wished to discontinue the treatment when their child’s condition improved. In Thaci research,[20] about 80% of patients achieved PASI 90 at Week 16. From the data of Table 3, more than 88% of patients achieved PASI 90 at 8 weeks in secukinumab group, which shows a follow-up of 8 weeks is sufficient in our dataset, The sample size and follow-up duration can be further improved in the future.
To our knowledge, there is limited research on the secukinumab used in Chinese pediatric patients with moderate to severe plaque psoriasis, and these studies mainly focused on the past 3 years. Miao et al reported 20 children treated with secukinumab recovered (Japanese Dermatological Association Severity Index score: 0/1) within 3 weeks.[21] Yu et al also reported the average time to achieve PASI 75 in 22 patients using secukinumab was 3.2 ± 1.8 weeks.[22] Furthermore, there are also some studies indicated successful treatment with secukinumab monotherapy for generalized pustular psoriasis and severe scalp and nail involvement caused by the IL36RN gene mutation.[23,24]
The PASI improvement rates of children with moderate to severe plaque psoriasis treated with secukinumab for 4 and 8 weeks were higher than those of children receiving conventional non-biologic treatments. The PASI 90 response rate was 58.33% at week 4 and 91.67% at week 8 in the secukinumab group. These results are consistent with data from the randomized phase III study of secukinumab conducted by Nina Magnolo in children with moderate to severe plaque psoriasis.[11]
Although conventional non-biologic therapy can alleviate the severity of skin lesions in children, the therapeutic outcome is not ideal, making it difficult to achieve the treatment goal of complete clearance of skin lesions. After 4 weeks of treatment, there was no difference in DLQI 0/1 response rate and IGA 0/1 response rate between the 2 groups. After 8 weeks of treatment, the 2 parameters in secukinumab group and secukinumab without pre-traditional treatment group were higher than those in the conventional group (P < .05), which showed secukinumab can improve the life quality and reduce the severity of skin lesions.
In addition, children with moderate to severe plaque psoriasis who had not been treated with traditional systemic therapies before had better early responses to secukinumab than those treated with conventional therapies before. At week 4, all children without traditional systemic therapies achieved PASI 75, and the improvement rate of PASI was higher in those patients who had not been treated with pre-traditional systemic therapies. The reason might be involving the nonspecific anti-inflammatory effects of traditional treatment drugs, which indirectly affects the immune types of psoriasis and their response to biological agents. At week 8, there were no differences in PASI improvement rate and IGA 0/1 response rate between the 2 subgroups, which further verified the reliable efficacy of secukinumab in treating children with moderate to severe plaque psoriasis. At the same time, there was no difference in DLQI 0/1 response rate at week 4 and week 8 in the treatment of children with psoriasis with or without pre-traditional systemic treatments, indicating that secukinumab could improve the life quality of patients.
Finally, no severe adverse effects were observed in the secukinumab treatment of pediatric patients with moderate to severe plaque psoriasis in China.
Acknowledgments
We thank all the participants in this study for their cooperation and support.
Author contributions
Conceptualization: Yuping Zhang, Long Wang.
Data curation: Xiji Lu.
Formal analysis: Ying Zhou, Ni Liang.
Investigation: Liqing Lei.
Methodology: Liqing Lei.
Supervision: Chen Li.
Writing – review & editing: Chen Li.
Abbreviations:
- AE
- adverse events
- BSA
- body surface area
- DLQI
- Dermatology Life Quality Index
- IGA
- Investigator’s Global Assessment
- IgG1
- immunoglobulin G1
- IL
- interleukin
- PASI
- Psoriasis Area and Severity Index
- TNF-α
- tumor necrosis factor-α
The ethics of this study was approved by Peking University First Hospital Biomedical Research Ethics Committee (NO.2020yan255-001-Amendment), and the Ethics Committee of Clinical Research and Laboratory Animals at Zhongshan City People’s Hospital (NO.K2022-275). Informed consent was written and obtained from participants (or their parents/legal guardians/next of kin). This study was conducted ethically in accordance with the World Medical Association Declaration of Helsinki.
The authors have no funding and conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
How to cite this article: Zhang Y, Lu X, Zhou Y, Lei L, Wang L, Liang N, Li C. Efficacy of secukinumab in pediatric patients with moderate to severe plaque psoriasis: A randomized study. Medicine 2025;104:46(e46058).
Contributor Information
Yuping Zhang, Email: zyping0820@163.com.
Xiji Lu, Email: 1012604614@qq.com.
Ying Zhou, Email: 1397068673@qq.com.
Liqing Lei, Email: knowking@qq.com.
Long Wang, Email: 414110094@qq.com.
Ni Liang, Email: nileong@qq.com.
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