Guselkumab Efficacy by Psoriasis Disease Severity and Treatment History: VOYAGE 1 and 2 Post Hoc Analyses
Guselkumab Efficacy by Psoriasis Disease Severity and Treatment History: VOYAGE 1 and 2 Post Hoc Analyses
Gordon KB, Merola JF, Foley P, Choi O, Chan D, Miller M, You Y, Shen YK, Patel HV, Blauvelt A. Guselkumab Efficacy by Psoriasis Disease Severity and Treatment History: VOYAGE 1 and 2 Post Hoc Analyses. J Drugs Dermatol. 2025;24(2):196-202. doi:10.36849/JDD.8344.
Introduction
Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by erythematous plaques and scaling, significantly impairing quality of life. Managing moderate-to-severe psoriasis poses a clinical challenge due to disease heterogeneity and varying patient treatment histories. Guselkumab, a monoclonal antibody targeting interleukin-23, has emerged as a potent treatment option demonstrating efficacy in skin clearance.
The pivotal Phase 3 VOYAGE 1 and VOYAGE 2 trials established guselkumab’s clinical benefit. This article presents post hoc analyses assessing the durability of guselkumab’s efficacy over 5 years (through week 252) across subgroups stratified by baseline disease severity characteristics and prior therapies, offering insights into long-term treatment effectiveness in routine clinical scenarios.
Study Overview
Study Type: Phase 3 randomized controlled trials with open-label extension and post hoc analyses
Population: Adult patients with moderate-to-severe psoriasis enrolled in VOYAGE 1 and 2 studies
Intervention: Guselkumab 100 mg every 8 weeks, with initial comparators placebo and adalimumab
Outcomes: Sustained Investigator’s Global Assessment (IGA 0/1) and PASI 90 responses from week 100 to week 252 across prespecified subgroups
Subgroups included stratification by baseline PASI (<20 vs ≥20), baseline IGA (=3 vs =4), baseline body surface area (BSA; <20% vs ≥20%), and prior treatment history, including phototherapy, nonbiologic systemic, and biologic therapy use. Analysis was conducted on observed data applying predefined treatment failure rules.
- Sustained response rates achieved between weeks 100 and 252 were consistent across baseline disease severity groups: IGA 0/1 rates ranged from 81.1% to 85.4%, PASI 90 rates from 78.6% to 83.8%.
- Baseline PASI stratification showed similar efficacy: IGA 0/1 at 82.0%-85.4% for PASI <20 and 81.1%-81.4% for PASI ≥20; PASI 90 at 78.6%-81.1% and 81.4%-83.8%, respectively.
- Baseline IGA levels also sustained efficacy: IGA 0/1 at 82.7%-85.4% for IGA=3 and 77.6%-79.0% for IGA=4; PASI 90 at 79.1%-82.7% and 79.7%-82.9% respectively.
- BSA stratification revealed similarly high response rates: IGA 0/1 82.5%-86.2% (<20%) vs 81.1%-82.6% (≥20%); PASI 90 80.4%-82.7% vs 79.1%-82.0%.
- Prior phototherapy and nonbiologic use subgroups maintained robust responses, with IGA 0/1 and PASI 90 rates exceeding 79% in all cases.
- Patients with prior biologic therapy exhibited somewhat reduced response rates: IGA 0/1 75.3%-79.5%, PASI 90 71.2%-76.3%, compared to biologic-naïve patients.
Evidence Synthesis
This post hoc pooled analysis by Gordon et al. (2025) affirms guselkumab’s sustained efficacy over 5 years across a wide spectrum of clinical presentations and treatment histories. Importantly, response durability was observed regardless of baseline severity measures or prior therapies, reinforcing guselkumab’s role as a versatile long-term treatment option.
Supporting Data from Related Research
- Lebwohl et al., 2023: Pooled analyses from seven trials including VOYAGE studies reported a favorable long-term safety profile for guselkumab with no new safety concerns over 8600+ patient-years (PMID: 37022762), a critical companion to efficacy data.
- Puig et al., 2024: Post hoc analysis of VOYAGE 1 patients achieving complete skin clearance (PASI=0) found higher early plasma guselkumab concentration predicted sustained clearance, highlighting pharmacokinetic predictors of durable response (PMID: 37804472).
- Kim et al., 2023: Subpopulation analysis in Asian patients demonstrated comparable sustained efficacy and safety through 5 years, confirming generalizability across geographic and ethnic populations (PMID: 37750995).
Summary Table: Key Evidence Comparison
| Study | Population | Duration | Findings | Relevance |
|---|---|---|---|---|
| Gordon et al., 2025 | Moderate-to-severe psoriasis patients VOYAGE 1 & 2 | 5 years (week 252) | Durable IGA 0/1 and PASI 90 response across severity & treatment history subgroups | Strong evidence for long-term efficacy regardless of baseline severity or prior therapy |
| Lebwohl et al., 2023 | Multiple trials pooled, 8600+ PY | Up to 5 years | Favorable safety profile without increased serious AEs or infections | Supports long-term treatment safety complementing efficacy data |
| Puig et al., 2024 | Subset of VOYAGE 1 patients with PASI=0 maintained | ~3 years continuous clearance | Early high plasma drug levels predict sustained skin clearance | Pharmacokinetic insight for optimizing durable responses |
| Kim et al., 2023 | Asian psoriasis patients VOYAGE 1 & 2 | 5 years | Sustained efficacy and consistent safety profile similar to global cohorts | Evidence for applicability across ethnic groups |
Clinical Implications
- Guselkumab provides sustained high-level skin clearance for moderate-to-severe psoriasis patients over 5 years, supporting its use as a durable long-term treatment.
- Response durability spans patients with varying baseline disease severity and prior treatment histories, including biologic-experienced subpopulations, indicating broad therapeutic applicability.
- Clinicians can counsel patients regarding likely sustained efficacy and favorable safety profile, aiding shared decision-making and adherence.
- Recognizing somewhat lower response rates in biologic-experienced patients may inform monitoring and therapy expectations.
Strengths & Limitations
| Strengths | Limitations |
|---|---|
| Large sample sizes pooled from two pivotal Phase 3 RCTs with extended long-term follow-up (5 years) | Post hoc nature of analyses; potential bias despite randomized baseline population |
| Comprehensive subgroup analyses by multiple clinically relevant stratifiers (PASI, IGA, BSA, prior treatment) | Open-label extension phase without active comparator after week 52, limiting comparative assessments beyond 1 year |
| Use of robust, validated efficacy endpoints (IGA 0/1, PASI 90) consistently measured over 5 years | Possible selection bias from treatment failure rules and observed data approach, may affect generalizability |
| Confirmation by related literature on safety and specific subpopulations strengthens interpretation | Limited ethnic diversity information outside Asian subgroup analysis |
Future Directions
Further prospective studies evaluating guselkumab treatment responses in diverse and biologic-experienced populations are warranted to optimize individualized treatment strategies. Exploring pharmacokinetic predictors and real-world safety monitoring will enhance personalized psoriasis care.
Conclusion
Guselkumab exhibits durable efficacy sustained through 5 years of treatment across varied psoriasis severities and treatment histories, underscoring its value as a long-term therapeutic option for moderate-to-severe psoriasis.
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References
- Gordon, K. B., Merola, J. F., Foley, P., et al. (2025). Guselkumab Efficacy by Psoriasis Disease Severity and Treatment History: VOYAGE 1 and 2 Post Hoc Analyses. J Drugs Dermatol, 24(2), 196–202. PMID: 39913230.
- Kim, B. S., Jo, S. J., Youn, S. W., et al. (2023). Five-year Maintenance of Clinical Response and Consistent Safety Profile for Guselkumab in Asian patients with Psoriasis from VOYAGE 1 and VOYAGE 2. Dermatol Ther, 13(11), 1026–1035. PMID: 37750995.
- Lebwohl, M. G., Merola, J. F., Rowland, K., et al. (2023). Safety of guselkumab treatment for up to 5 years in patients with moderate-to-severe psoriasis: pooled analyses across seven clinical trials with more than 8600 patient-years of exposure. Br J Dermatol, 189(1), 77–86. PMID: 37022762.
- Puig, L., Costanzo, A., de Jong, E. M., et al. (2024). Guselkumab-Treated Patients with Plaque Psoriasis Who Achieved Complete Skin Clearance for ≥ 156 Consecutive Weeks: A Post-Hoc Analysis From the VOYAGE 1 Clinical Trial. Am J Clin Dermatol, 25(2), 335–346. PMID: 37804472.
