GPP Therapies: Comparing Efficacy and Safety of Secukinumab and Ustekinumab

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While the disease’s mechanisms are not fully understood, several genetic factors are implicated in generalized pustular psoriasis (GPP), including mutations in IL36RN and CARD14.Treatment for GPP is complex due to its recurrent nature; Traditional therapies like acitretin and methotrexate have significant adverse events, making them less ideal for long-term use. Novel biologics, such as spesolimab, ustekinumab, and secukinumab, are showing promise, with recent studies indicating these biologics can lead to better outcomes, including fewer complications and lower mortality rates.¹

GPP involves both innate and adaptive immune responses, with key roles for the IL-1/IL-36 and IL-23/IL-17 pathways. Although spesolimab has recently entered the market, long-term data on its effectiveness is limited. Researchers have recognized ustekinumab and secukinumab as viable treatment options, particularly in China, though their comparative efficacy and safety remain under investigation.

A recent study aimed to explore the efficacy differences between the IL-17A inhibitor (secukinumab) and the IL-12/23p40 inhibitor (ustekinumab) in treating GPP, as well as whether CARD14 mutations influence treatment responses.²

“We found that both ustekinumab and secukinumab effectively reversed the systemic inflammation and skin symptoms of GPP, with sustained improvement observed for up to 48 weeks,” researchers reported.

Study Design and Patients

The study analyzed 65 patients with generalized pustular psoriasis (GPP), 33 children and 32 adults, admitted to the dermatology department between July 2019 and May 2022. Patients were treated with either ustekinumab (31 patients) or secukinumab (34 patients), with a follow-up duration of 48 weeks.

Genomic DNA was isolated from saliva samples, according to the study, and targeted re-sequencing identified mutations in GPP-associated genes (e.g., IL36RN, CARD14) at a clinical laboratory.Patients underwent routine assessments before receiving ustekinumab or secukinumab. Researchers stated that ustekinumab dosing was weight-adjusted, while secukinumab was given based on specific weight categories. 

Clinical Efficacy

Researchers found secukinumab demonstrated faster improvements in temperature, white blood cell counts, C-reactive protein (CRP), and serum albumin levels compared to ustekinumab. Notably, they found a significantly higher percentage of patients on secukinumab achieved GPPASI 75 and 90 responses at weeks 1 and 2. The mean time to pustule disappearance was shorter for secukinumab (3.00 days) versus ustekinumab (4.26 days), indicating its rapid action.

Quality of Life Improvements

Researchers found that both treatments improved health-related quality of life (HRQoL), but secukinumab showed quicker improvements in the pediatric quality of life inventory and the short form health survey scores at week 2. By week 48, researchers stated that 86.15% of patients achieved a children's dermatology life quality index/dermatology life quality index score of 0 or 1, with no significant differences between the 2 groups in the later follow-ups.

Genetic Mutations

Researchers found that mutations in the CARD14 gene were prevalent (44.61%), yet these did not correlate with improved treatment responses to either ustekinumab or secukinumab. This suggested the themthat the IL-23/IL-17A pathway is crucial in GPP pathogenesis, independent of genetic mutations.

Safety Profile

Both ustekinumab and secukinumab were well tolerated over 48 weeks, according to the study, with adverse effects comparable to prior data. Researchers stated that common reactions included nasopharyngitis, urticaria, and injection site reactions. They stated a notable incidence of eczema-like reactions (9.23%) was observed, primarily in patients with atopic histories.

Conclusion

The study found that secukinumab outperformed ustekinumab in achieving rapid skin clearance and improving HRQoL for GPP patients. Both treatments were found to be safe and effective, but further research in larger, controlled trials is needed to confirm these findings.

References

1. Fujita H, Terui T, Hayama K, et al. Japanese guidelines for the management and treatment of generalized pustular psoriasis: The new pathogenesis and treatment of GPP. J Dermatol. 2018;45(11):1235-1270. doi:10.1111/1346-8138.14523
2. Ruan SF, Su X, Xiao Z, et al. Comparative efficacy and safety of ustekinumab and secukinumab in the treatment of generalized pustular psoriasis: A 48-week retrospective cohort study with genetic background analysis. J Inflamm Res. 2024;17:6707-6721. 2024. doi:10.2147/JIR.S472338