New research indicates that secukinumab is more effective than ustekinumab in rapidly clearing skin in patients with generalized pustular psoriasis (GPP). The study, led by Shi-Fan Ruan from The First Affiliated Hospital of Fujian Medical University in China, compared the efficacy and safety of the two drugs, both approved in Japan for treating GPP in adults.
Study Details and Patient Population
The retrospective study included 65 patients with moderate to severe GPP, with 34 receiving secukinumab and 31 receiving ustekinumab. The participants, aged 2 to 83 years, were followed for 48 weeks. Inclusion criteria required patients to meet GPP diagnostic criteria, have an average GPPGA score ≥ 3, and have discontinued non-biologic treatments before starting ustekinumab or secukinumab. Nearly half of the participants (47.69%) had a prior diagnosis of psoriasis vulgaris.
Efficacy Comparison
The study assessed changes in body temperature, laboratory indices, skin lesion recovery, and quality of life. Secukinumab demonstrated faster improvements in temperature, WBC, CRP, and serum albumin levels. Most patients' temperatures normalized within 7 days of treatment. CRP levels showed a more significant reduction in the secukinumab group (P = .005). Serum albumin levels significantly increased in both groups by week 2, but the increase was more pronounced in the secukinumab group by week 3 (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%) compared to those taking ustekinumab (9.68%) (treatment difference, 31.50 percentage points; 95% confidence interval [CI], 1.67 – 25.78; P < .001). This trend continued at week 2, with 73.53% on secukinumab versus 51.61% on ustekinumab achieving a GPPASI 75 response (treatment difference, 21.92 percentage points; 95% CI, 0.92 – 7.35; P = .047). The mean time for pustule disappearance was significantly shorter for secukinumab (3.00±1.23 days) compared to ustekinumab (4.26±1.41 days) (P = .0003).
Genetic Influence
Approximately 44.62% of participants had gene mutations in either CARD14 (44.61%) or IL36RN (1.54%). However, CARD14 mutations did not correlate with greater response rates regarding GPPASI 90 at weeks 2, 4, 12, 24, and 48. This suggests that the CARD14 gene mutation is not linked to the clinical response to either ustekinumab or secukinumab.
Implications for GPP Treatment
"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," the 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."
