Secukinumab Demonstrates High Efficacy and a Favorable Safety Profile Over 52 Weeks in Chinese Patients with Moderate to Severe Plaque Psoriasis
Introduction
Psoriasis, a chronic inflammatory skin disease, affects approximately 0.6% of the Chinese population. Characterized by erythematous, scaly plaques, the disease significantly impacts quality of life (QoL) and is associated with comorbidities such as psoriatic arthritis, cardiovascular diseases, and metabolic syndrome. In China, a nationwide study revealed that 57.3% of psoriasis patients have moderate to severe disease, yet conventional treatments—including topical agents, phototherapy, and traditional Chinese medicines (TCMs)—often fail to provide adequate control. This unmet need underscores the demand for targeted therapies with sustained efficacy and safety.
Secukinumab, a fully human monoclonal antibody targeting interleukin (IL)-17A, has demonstrated robust efficacy in global Phase 3 trials. IL-17A is a key driver of psoriasis pathogenesis, promoting keratinocyte proliferation and inflammatory responses. While previous studies included Asian subpopulations, dedicated trials in Chinese patients were limited. This Phase 3b study (NCT03066609) evaluated the efficacy and safety of secukinumab over 52 weeks in Chinese patients with moderate to severe plaque psoriasis.
Methods
Study Design and Participants
This multicenter, randomized, double-blind, placebo-controlled trial enrolled 441 Chinese adults (≥18 years) with moderate to severe plaque psoriasis (Psoriasis Area Severity Index [PASI] ≥12, Investigator’s Global Assessment [IGA] score ≥3, and body surface area [BSA] involvement ≥10%). Participants were randomized 2:1:1 to receive subcutaneous secukinumab 300 mg, 150 mg, or placebo at Baseline, Weeks 1–4, and every 4 weeks thereafter. At Week 12, placebo non-responders (PASI 75 non-achievers) were switched to secukinumab 300 mg.
Outcomes and Assessments
Co-primary endpoints were the proportion of patients achieving PASI 75 (≥75% reduction in baseline PASI) and IGA 0/1 (clear/almost clear skin) at Week 12. Key secondary endpoints included PASI 90/100 responses, absolute PASI scores, and Dermatology Life Quality Index (DLQI) 0/1 (no QoL impairment). Safety assessments monitored adverse events (AEs), serious AEs (SAEs), and immunogenicity (anti-drug antibodies [ADAs]).
Statistical Analysis
Sample size calculations assumed 10% placebo response rates for PASI 75 and IGA 0/1. Logistic regression models adjusted for baseline PASI, body weight, and region, with multiple imputation for missing data. Sensitivity analyses used non-responder imputation.
Results
Patient Characteristics
Baseline demographics were balanced across groups. Patients had severe disease burden: mean PASI 26.8, BSA 45.4%, and 44.7% classified as IGA 4 (severe). Mean disease duration was 15.3 years, and 18.1% had prior biologic exposure.
Efficacy Outcomes
Week 12 Responses
- PASI 75: Secukinumab 300 mg and 150 mg achieved 97.7% and 87.2% responses vs. 3.7% for placebo (P <0.001).
- IGA 0/1: Response rates were 82.3% (300 mg) and 69.7% (150 mg) vs. 2.7% (placebo) (P <0.001).
- PASI 90: Secukinumab 300 mg and 150 mg showed 81.0% and 65.7% responses vs. 0.9% for placebo (P <0.001).
- PASI 100: Complete clearance rates were 32.9% (300 mg) and 20.0% (150 mg) vs. 0% (placebo).
Sustained Efficacy Through Week 52
- PASI 75/90/100: Responses remained high at Week 52: 95.4%, 82.1%, and 42.1% (300 mg); 85.0%, 66.7%, and 31.5% (150 mg).
- Absolute PASI: Mean scores dropped from 26.8 at baseline to 1.4 (300 mg) and 3.0 (150 mg) by Week 52.
- DLQI 0/1: By Week 52, 47.5% (300 mg) and 34.5% (150 mg) reported no QoL impairment vs. 1.8% (placebo at Week 12).
Placebo non-responders switched to secukinumab 300 mg at Week 12 achieved response rates comparable to the original 300 mg group by Week 28.
Safety Profile
- Overall AEs: Exposure-adjusted incidence rates (EAIRs) were 345.5/100 patient-years (secukinumab) vs. 536.9/100 patient-years (placebo), indicating no increased risk with active treatment.
- Infections: Most common AEs (e.g., nasopharyngitis, upper respiratory infections) occurred at comparable rates (secukinumab: 107.4/100 patient-years; placebo: 110.9/100 patient-years).
- SAEs: Low incidence (3.0/100 patient-years secukinumab vs. 3.5/100 patient-years placebo). Four SAEs led to discontinuation (Crohn’s disease, pyrexia, pemphigus, mouth ulceration).
- Immunogenicity: ADAs were detected in 12 patients (4 transient; no impact on efficacy or safety).
Discussion
This trial confirms secukinumab’s superior efficacy and safety in Chinese patients, aligning with global studies while addressing unique population characteristics. Notably, baseline disease severity in this cohort exceeded that of Western trials (mean PASI 26.8 vs. 22.1–23.7 in ERASURE/FIXTURE), yet secukinumab achieved higher response rates—97.7% PASI 75 vs. 77.7–81.6% in prior studies. Potential contributors include lower body weight (73.0 kg vs. 83.3–88.5 kg in Western cohorts) and fewer smokers (62.6% vs. 41.9–58.1%), factors associated with improved therapeutic responses.
The rapid onset of action (median time to PASI 75: 52 days for 300 mg) and sustained efficacy through 52 weeks highlight secukinumab’s value as a long-term therapy. Importantly, the 300 mg dose consistently outperformed 150 mg, supporting its use in severe cases. Safety findings mirrored global data, with no new signals, reinforcing secukinumab’s favorable risk-benefit profile.
Compared to other biologics in Chinese populations, secukinumab demonstrated higher efficacy than adalimumab (77.8% PASI 75) and ustekinumab (82.5% PASI 75), with comparable safety.
Conclusion
Secukinumab 300 mg and 150 mg provided rapid, durable efficacy and acceptable safety over 52 weeks in Chinese patients with moderate to severe plaque psoriasis. The 300 mg dose is recommended for optimal outcomes, particularly in severe disease. These results address critical gaps in psoriasis management for Chinese patients, offering a transformative therapeutic option.
doi.org/10.1097/CM9.0000000000001163
Was this helpful?
0 / 0