Secukinumab Surpasses Ustekinumab in Clearing Skin for Generalized Pustular Psoriasis

New research found secukinumab is superior to ustekinumab in rapidly clearing the skin for patients with generalized pustular psoriasis (GPP).¹

“Our study demonstrated that secukinumab acted rapidly, as a significantly higher proportion of patients receiving secukinumab achieved efficacy responses at week 1 and 2 compared to those receiving ustekinumab,” wrote investigators, led by Shi-Fan Ruan, from The First Affiliated Hospital of Fujian Medical University in China.

Ustekinumab and secukinumab are both approved in Japan for treating GPP in adult patients. Although studies have shown both drugs provide significant clinical benefits for this skin condition, it was unknown how the two drugs compared in efficacy and safety.²

In a recent retrospective study, investigators sought to compare the efficacy and safety of secukinumab and ustekinumab in patients with GPP.¹ The trial included patients with moderate to severe GPP who were treated with ustekinumab (n =31) or secukinumab (n = 34) at the department of dermatology in the First Affiliated Hospital of Fujian Medical University from July 2019 to May 2022. Participants were followed up for 48 weeks.

The sample had 65 patients, with 33 children and 32 adults. Participants were aged 2 – 83 years, with a mean age of 36.00±18.97 years in the ustekinumab group and 22.92±21.07 years in the secukinumab group. Participants were included if they met the diagnostic criteria for GPP, had a moderate to severe disease defined as an average GPPGA score of ≥ 3, and discontinued the treatment with non-biologic agents before they started the treatment with ustekinumab or secukinumab.

Nearly half of the sample (47.69%) had been diagnosed with psoriasis vulgaris before GPP. Participants in the ustekinumab and secukinumab groups had a mean GPPASI score of 25.16±7.64 and 22.92±21.07, respectively.

The team compared the efficacy of the drugs by assessing body temperature changes, laboratory indices, recovery of skin lesions, and quality of life changes. Investigators also collected patients’ saliva for genotyping and explored whether CARD14 genetic mutations influenced the response to ustekinumab or secukinumab.

Participants on secukinumab had faster improvement in temperature, WBC, CRP, and serum albumin than those on ustekinumab. Most patients’ temperatures returned to normal 7 days after treatment.

In both groups, WBC counts were restored in the first week. The CRP levels, which had no observed differences between groups before treatment (P > .05) had a more significant reduction in those who were on secukinumab (P = .005). As for serum albumin, it was significantly increased and returned to normal levels by week 2 in both groups, but by week 3, the increase was more noticeable in the secukinumab group than the ustekinumab group (at week 1, P = .041; at week 2, P < .0001; at week 3, P < .0001).

A significantly greater proportion of participants taking secukinumab achieved a GPPASI 75 response at week 1 (41.8%) vs those taking ustekinumab (9.68%) (treatment difference, 31.50 percentage points; 95% confidence interval [CI], 1.67 – 25.78; P < .001), and this was also seen at week 2 (73.53% vs 51.61) (treatment difference, 21.92 percentage points; 95% CI, 0.92 – 7.35; P = .047).

Furthermore, 35% on secukinumab vs 6.45% on ustekinumab achieved a GPPASI response at week 2 (treatment difference, 28.55 percentage points; 95% CI, 1.60 – 39.03; P = .012). However, after week 4, the number of participants achieving GPPASI 75 and 90 responses was also similar between groups.

During the 48-week follow-up period, more patients on secukinumab achieved a GPPASI 100 response but there was no statistical significance. Ultimately, the mean time of disappearance of pustules was 4.26±1.41 days for patients on ustekinumab and 3.00±1.23 days for those on secukinumab—and the difference was statistically significant (P = .0003).

In total, 44.62% had gene mutations, either in CARD14 (44.61%) or IL36RN (1.54%), and 55.38% did not. Investigators saw patients with CARD14 mutations did not have greater response rates than those without mutations regarding GPPASI 90 at weeks 2, 4, 12, 24, and 48. The results indicate the CARD14 gene mutation is not linked to the clinical response to ustekinumab or secukinumab.

“The observation that ustekinumab and secukinumab demonstrated efficacy in patients with and without CARD14 genetic mutations suggests that the IL-23/IL-17A immune pathway plays a key role in GPP pathogenesis, regardless of the presence of genetic alterations,” investigators wrote. “This immune pathway serves as a bridge between innate and adaptive immunity, involving the activation of IL-36 and promoting the chemotaxis and aggregation of inflammatory cells (eg, neutrophils) at sites of inflammation.”

References

1. ^{Ruan SF, Su X, Xiao Z, Zhang Y, Lin T, Luo R, Xiang N, Cheng B, Gong T, Ji C. 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;17:6707-6721https://doi.org/10.2147/JIR.S472338}
2. ^{Samotij D, Szczęch J, Reich A. Generalized pustular psoriasis: divergence of innate and adaptive immunity. Int J Mol Sci. 2021;22(16):9048. doi:10.3390/ijms22169048}