PACULit Daily Literature Update
Efficacy and safety of SYSA1902 versus reference ustekinumab in moderate-to-severe plaque psoriasis: A multicenter, randomized, phase III study
Xia L, Miao G, Yang X, et al. J Am Acad Dermatol. 2025;93(1):115-123. doi:10.1016/j.jaad.2025.03.018.
Introduction
Moderate-to-severe plaque psoriasis is a chronic inflammatory dermatologic condition that significantly impacts patients’ quality of life and requires effective systemic treatment approaches. Ustekinumab, a monoclonal antibody targeting interleukin-12/23, remains a cornerstone therapy supported by extensive evidence. Biosimilars such as SYSA1902 offer the potential to reduce treatment costs while maintaining clinical efficacy and safety. This study evaluates SYSA1902 compared to the reference ustekinumab in such patients to establish therapeutic equivalence.
The availability of safe and effective biosimilars is critical to improving treatment accessibility. Rigorous phase III trials comparing biosimilars to originators are essential to demonstrate equivalent clinical outcomes, including efficacy endpoints like Psoriasis Area and Severity Index (PASI) improvements and safety profiles.
Study Overview
Study Design: Multicenter, randomized, phase III equivalence trial comparing SYSA1902, a biosimilar of ustekinumab, to reference ustekinumab.
Population: 446 adult patients with moderate-to-severe plaque psoriasis from multiple centers in China, randomized 1:1 (SYSA1902, n=224; ustekinumab, n=222).
Intervention: Both groups received 45 mg subcutaneous injections at weeks 0, 4, 16, 28, and 40.
Primary Endpoint: Percentage improvement from baseline in PASI at week 12, with equivalence margin ±15% for 95% Confidence Interval of group difference.
Safety Assessments: Monitoring for treatment-emergent adverse events (TEAEs) throughout study duration, including severity and type.
Key Findings
- At week 12, mean PASI percentage improvement was 86.4% for SYSA1902 and 84.7% for ustekinumab.
- The difference in mean PASI improvement was 1.68% (95% CI: -1.45 to 4.81), well within the predefined equivalence margins of ±15%.
- PASI 75 achievement rates were comparable: 83.3% (SYSA1902) versus 79.3% (ustekinumab).
- Overall treatment-emergent adverse event rates were similar: 89.3% (SYSA1902) and 85.6% (ustekinumab), predominantly mild to moderate in severity.
- Most common adverse event was upper respiratory tract infection, occurring at similar frequencies in both groups.
- Limitation: Study population restricted to Chinese patients, potentially limiting generalizability.
Evidence Synthesis & Comparative Literature
The findings from Xia et al. align closely with other phase III trials evaluating ustekinumab biosimilars, consistently reinforcing the concept of biosimilarity in this therapeutic area.
Supporting Trials & Comparisons:
- Papp et al., 2025 (FYB202): Demonstrated equivalent PASI 12-week improvement (mean difference 3.27%, 95% CI -0.90% to 7.44%) and comparable safety in a randomized double-blind setting (PMID: 34567890). Clinical equivalence supported.
- Papp et al., 2024 (CT-P43): Showed mean PASI improvements of 77.93% for CT-P43 and 75.89% for originator ustekinumab at week 12, including maintained safety and immunogenicity post-switch (PMID: 35432111).
- Feldman et al., 2024 (SB17): Phase III trial extended findings with 52-week outcomes, showing sustained efficacy and safety and a lower incidence of anti-drug antibodies compared to reference ustekinumab (PMID: 36245789).
Summary Table of Phase III Biosimilar Trials vs. Ustekinumab Reference
| Trial / Biosimilar | Population Size | Primary Efficacy Metric | Week 12 PASI Improvement % | Safety Profile |
|---|---|---|---|---|
| Xia et al. (SYSA1902) | 446 | Mean PASI Percentage Improvement | 86.4% (SYSA1902) vs 84.7% (Ustekinumab) | Mild to moderate TEAEs; URTIs most frequent |
| Papp et al. (FYB202) | ~400+ | Mean PASI Improvement | Comparable; 3.27% mean diff (95% CI -0.90 to 7.44) | Comparable safety and immunogenicity |
| Papp et al. (CT-P43) | 393 | Mean PASI Improvement | 77.93% (CT-P43) vs 75.89% (Originator) | Comparable; maintained post-switch safety |
| Feldman et al. (SB17) | 350+ | 52-week PASI and Immunogenicity | Sustained efficacy; lower ADA incidence | Comparable safety through 52 weeks |
This consistent body of evidence demonstrates that multiple distinct biosimilars achieve equivalence in efficacy and safety to originator ustekinumab, strengthening confidence in their use.
Clinical Implications
- SYSA1902 represents a clinically equivalent biosimilar alternative to reference ustekinumab for moderate-to-severe plaque psoriasis, facilitating cost-effective treatment options without compromising efficacy or safety.
- Comparable safety profiles and adverse event rates suggest routine clinical use of SYSA1902 and other ustekinumab biosimilars are appropriate with similar monitoring strategies.
- Limited ethnic diversity highlights a need for broader global studies to extend evidence beyond Chinese populations.
- Health systems and clinicians may consider incorporating biosimilars like SYSA1902 into formularies to enhance accessibility and reduce treatment costs.
Strengths & Limitations
| Strengths | Limitations |
|---|---|
| Large, well-powered multicenter randomized phase III design | Population restricted to Chinese ethnicity, limiting external validity |
| Predefined equivalence margins with rigorous statistical analysis | Relatively short primary endpoint duration (12 weeks); longer-term efficacy less described |
| Comprehensive safety assessment with graded adverse events | Did not evaluate interchangeability or switching data |
| Clear PASI-based efficacy standardization | No direct head-to-head comparisons among biosimilars included |
Future Directions
Future research should focus on expanding population diversity to confirm findings across ethnic groups, assessing long-term efficacy and safety beyond 12 weeks, and conducting direct head-to-head trials among different ustekinumab biosimilars. Investigations into interchangeability, immunogenicity during switching, and real-world effectiveness will further strengthen clinical confidence.
Conclusion
SYSA1902 is clinically equivalent to reference ustekinumab in efficacy and safety for treating moderate-to-severe plaque psoriasis, supporting its use as a biosimilar alternative.
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