Low-Dose Secukinumab Shows Best PASI 90 in Pediatric Plaque Psoriasis

Among approved biologic regimens for pediatric patients with moderate to severe plaque psoriasis, low-dose secukinumab (SEC-L) may provide the most improvement in disease severity without increasing the risk for discontinuing treatment due to an adverse event, says a review of randomized controlled trials published in Journal of the German Society of Dermatology.

The analysis of 5 studies between 2004 and 2019 found that, compared with placebo, all biologic regimens improved Psoriasis Area and Severity Index 90 (PASI 90) response—considered a gold standard goal due to its correlation with quality of life.

Biologic regimens used in the studies included SEC-L, etanercept (ETN), ixekizumab (IXE), standard-dose ustekinumab (UST-SD), and high-dose adalimumab (ADA-H). By 12 to 16 weeks, the regimens demonstrated a significantly higher PASI 90 response vs placebo.

Surface under the cumulative ranking curve (SUCRA) showed that SEC-L had the strongest PASI 90 response (84.7%), followed by IXE (70.8%). Both treatments were significantly more efficient than ETN (risk ratio [RR], 2.59; 95% CI, 1.57-4.28; RR, 2.05, 95% CI, 1.34-3.14, respectively). UST-SD also showed improvement compared with ETN, although the difference was not significant.

“Potential variations in treatment efficacy between pediatric and adult psoriasis may originate from their different immunopathologic mechanisms. Despite the imbalance of regulatory and effector T cells in adult psoriasis, pediatric patients with psoriasis showed no elevation in the levels of regulatory T cells,” the study authors wrote. “Compared with adult psoriasis, the cutaneous infiltration of inflammatory cells and cytokines in the psoriatic lesions among pediatric patients was characterized by increased expression of IL [interleukin]-22 and less elevation of IL-17. In other words, the efficacy of biologic agents in treating pediatric psoriasis may differ from that in treating adult psoriasis, underscoring the importance of developing a potentially therapeutic target that is unique to pediatric psoriasis.”

The researchers also assessed Physician Global Assessment score (PGA) 0/1 and Children’s Dermatology Life Quality Index score (CDLQI) 0/1 among the regimens, finding that all biologic regimens showed significantly higher responses across both measures compared with placebo. Among biologics, UST-SD performed the best in PGA 0/1 (84.9%) and CDLQI 0/1 (81.9%) according to the SUCRA. The researchers noted that due to the small number of studies, comparisons between UST-SD and other biologic regimens were indirect comparisons, with placebo as a common baseline, and as a result, the potential intransitivity from the varying baseline disease severities in placebo groups should be considered.

At the same timepoint of 12 to 16 weeks, there were no significant differences in discontinuation rates for adverse events (DAE) between biologic regimens and placebo.

“Among all groups of treatment regimens, DAE appeared in only 2 participants, both from the placebo group—one participant from Bodemer et al and the other from Paller et al. Further specifications of the exact diagnosis of DAE are warranted to clarify the safety of biologic therapies,” the authors concluded. “The short time frame of the included RCTs may be speculated as a potential explanation for the low incidence of DAE. Therefore, studies with long-term follow-up are warranted.”

Reference

Huang I, Yu C, Tai C, Tu Y, Chi C. Biologics for pediatric moderate-to-severe plaque psoriasis: a systematic review and network meta-analysis. J Ger Soc Dermatol. Published online August 26, 2022. doi:10.1111/ddg.14832