Daily Literature Update
A Randomised, Double-Blind Trial to Compare the Efficacy, Safety, and Immunogenicity of the Biosimilar Ustekinumab FYB202 with Reference Ustekinumab in Patients with Moderate-to-Severe Plaque Psoriasis
Papp K, Balser S, Nopora K, et al. A Randomised, Double-Blind Trial to Compare the Efficacy, Safety, and Immunogenicity of the Biosimilar Ustekinumab FYB202 with Reference Ustekinumab in Patients with Moderate-to-Severe Plaque Psoriasis. Adv Ther. 2025;42(5):2135-2149. doi:10.1007/s12325-025-03138-2.
📖 Introduction
Moderate-to-severe plaque psoriasis is a chronic inflammatory skin condition that significantly impacts patients’ quality of life and often requires systemic biologic therapies for effective management. Ustekinumab, a monoclonal antibody targeting interleukin-12 and interleukin-23, has established efficacy and safety in this population. Biosimilars like FYB202 offer potential cost-effective alternatives to reference biologics, aiming to improve patient access and reduce healthcare expenditure.
This multicentre, randomised, double-blind trial evaluated whether the biosimilar ustekinumab FYB202 demonstrates therapeutic equivalence to the reference ustekinumab in terms of efficacy, safety, and immunogenicity in patients with moderate-to-severe plaque psoriasis.
📊 Study Design & Methodology
Study Type: Multicentre, randomised, double-blind equivalence trial
Population: 392 adults (≥18 years) with stable moderate-to-severe plaque psoriasis ≥6 months, inadequate response or intolerance to ≥1 systemic treatment
Intervention: FYB202 biosimilar vs reference ustekinumab, 1:1 randomisation; re-randomisation at week 28 for responders in reference group
Primary Endpoint: Percent improvement in PASI score from baseline to week 12; equivalence margins ±11% (95% CI) and ±10% (90% CI)
Additional Assessments: Safety and immunogenicity profiles; impact of switching from reference to FYB202
🔍 Key Findings
- 392 patients randomised: 197 to FYB202, 195 to reference ustekinumab; baseline characteristics well balanced
- Mean percent improvement in PASI at week 12 was equivalent: least-squares mean difference 3.27% (95% CI: -0.90%, 7.44%; 90% CI: -0.22%, 6.77%) within equivalence margins
- Safety and immunogenicity profiles comparable between FYB202 and reference groups
- Switching from reference ustekinumab to FYB202 did not affect efficacy, safety, or immunogenicity
🔬 Comprehensive Evidence Synthesis & Clinical Context
The findings of this trial are strongly supported by a consistent body of evidence from three rigorous Phase III clinical trials evaluating other ustekinumab biosimilars, which similarly demonstrated therapeutic equivalence and comparable safety and immunogenicity profiles.
🏛️ Parallel Phase III Trials
- Papp et al., 2024 (PMID: 37991693): CT-P43 biosimilar showed equivalent PASI improvement at week 12 and comparable safety versus reference ustekinumab.
- Feldman et al., 2024 (PMID: 38685404): SB17 biosimilar confirmed therapeutic equivalence and similar immunogenicity in moderate-to-severe plaque psoriasis.
- Blauvelt et al., 2025 (PMID: 39442018): ABP 654 biosimilar demonstrated sustained efficacy, safety, and immunogenicity through 52 weeks, including after switching from reference product.
🧩 Evidence Integration
Collectively, these studies validate the principle of ustekinumab biosimilarity, reinforcing the source study’s conclusions that FYB202 is an effective and safe alternative to reference ustekinumab. The safety of switching from reference to biosimilar is also well supported.
⚕️ Clinical Implications & Practice Recommendations
- FYB202 can be considered a therapeutically equivalent and safe biosimilar alternative to reference ustekinumab for moderate-to-severe plaque psoriasis.
- Switching patients from reference ustekinumab to FYB202 is clinically safe without loss of efficacy or increased immunogenicity.
- Use of biosimilars like FYB202 may improve patient access and reduce healthcare costs.
📝 Strengths & Limitations
| Strengths | Limitations |
|---|---|
| Robust multicentre, double-blind randomised design | Relatively short primary endpoint assessment at 12 weeks |
| Well-balanced baseline characteristics and adequate sample size (n=392) | Limited long-term efficacy and safety data beyond 28 weeks |
| Inclusion of switching analysis from reference to biosimilar | Generalizability to real-world populations requires further study |
🔮 Future Directions
Further research is needed to evaluate long-term efficacy and safety beyond 52 weeks, generate large-scale real-world evidence on biosimilar use, and conduct direct head-to-head comparisons between different ustekinumab biosimilars.
✅ Clinical Bottom Line
FYB202 demonstrated therapeutic equivalence to reference ustekinumab in moderate-to-severe plaque psoriasis, with comparable safety and immunogenicity, supporting its use as a cost-effective alternative.
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References
- Papp KA, Lebwohl MG, Thaçi D, et al. Efficacy and Safety of Candidate Biosimilar CT-P43 Versus Originator Ustekinumab in Moderate to Severe Plaque Psoriasis: 28-Week Results of a Randomised, Active-Controlled, Double-Blind, Phase III Study. BioDrugs. 2024;38(1):121-131. doi:10.1007/s40259-023-00637-z. PMID: 37991693.
- Feldman SR, Narbutt J, Girolomoni G, et al. A randomized, double-blind, phase III study assessing clinical similarity of SB17 (proposed ustekinumab biosimilar) to reference ustekinumab in subjects with moderate-to-severe plaque psoriasis. J Am Acad Dermatol. 2024;91(3):440-447. doi:10.1016/j.jaad.2024.04.038. PMID: 38685404.
- Blauvelt A, Papp K, Trivedi M, et al. Efficacy and safety of the ustekinumab biosimilar ABP 654 in patients with moderate-to-severe plaque psoriasis: a randomized double-blinded active-controlled comparative clinical study over 52 weeks. Br J Dermatol. 2025;192(5):826-836. doi:10.1093/bjd/ljae219. PMID: 39442018.
