Efficacy and Safety of Ustekinumab Biosimilars in the Treatment of Moderate-to-Severe Plaque Psoriasis: A Systematic Review and Meta-analysis.

BACKGROUND AND

OBJECTIVES

Psoriasis is a chronic, debilitating disease affecting 1-3% of the global population. Ustekinumab has been established as an effective therapy for moderate-to-severe plaque psoriasis, but its high cost limits patient access. Biosimilars offer a promising avenue to reduce costs and improve availability. Therefore, this study aimed to assess the efficacy, safety, and immunogenicity of biosimilars in comparison with ustekinumab.

METHODS

We comprehensively searched PubMed, Cochrane Library, Embase, and clinical trial registries from their inception through August 2025 for phase III randomized controlled trials (RCTs) that directly compared ustekinumab biosimilars with the reference product in patients with moderate-to-severe plaque psoriasis. Data on efficacy, safety, and immunogenicity were extracted. The primary outcome was the mean percent change in Psoriasis Area and Severity Index (PASI) from baseline at 12 weeks. Secondary outcomes included mean percent change in PASI from baseline at 28 and 52 weeks, mean change in Dermatology Life Quality Index (DLQI) score from baseline at 12 and 28 weeks, proportion of participants achieving a Physician's Global Assessment (PGA) score of 0 or 1 at 12 and 28 weeks, proportion of participants developing anti-drug antibodies (ADAs), and proportion of participants experiencing treatment-related adverse events (TRAEs). Risk ratios (RRs) and mean differences (MDs) were calculated using the random-effects models.

RESULTS

The meta-analysis included nine RCTs reported across ten studies (nine publications and one trial registry record). Nine RCTs (n = 4,532 total; n = 2,169 experimental; n = 2,363 control) contributed data on the primary outcome. The pooled mean difference (MD) was 0.44 (95% CI - 0.99 to 1.88, p = 0.54), indicating no statistically significant difference in PASI at 12 weeks between biosimilars and ustekinumab. Across all efficacy and safety outcomes, biosimilars demonstrated no statistically significant differences from ustekinumab except for three outcomes: the mean percent change in PASI at 28 weeks, the mean change in DLQI score at 28 weeks, and the presence of ADAs. Although the differences in PASI and DLQI at 28 weeks reached statistical significance, they were not considered clinically meaningful. For ADA development, the pooled RR was 0.68 (95% CI 0.55-0.85; p = 0.0005). However, this finding was associated with substantial heterogeneity (I2 = 71%) and very low-certainty evidence, warranting cautious interpretation. Additionally, the relatively short follow-up duration (≤ 52 weeks) and industry funding of all included trials are important limitations of this review.

CONCLUSION

Ustekinumab biosimilars demonstrated no clinically meaningful differences across the outcomes and sustained comparable efficacy across all time points. These findings suggest that ustekinumab biosimilars offer a therapeutic profile comparable in safety and efficacy to that of the originator, providing evidence in favour of their adoption, which may result in wider patient access to biologics and reduced healthcare costs.

PROSPERO: CRD420251133225.