Optimizing Psoriasis Treatment: GUIDE Trial Outcomes on Guselkumab Dosing

The GUIDE randomized clinical trial is an important study in the treatment of moderate-to-severe plaque psoriasis. It specifically evaluates the efficacy and safety of two dosing regimens of guselkumab, a human monoclonal antibody targeting interleukin-23 (IL-23), which is a key cytokine involved in the pathogenesis of psoriasis.

The standard dosing regimen of guselkumab for psoriasis involves an initial dose, followed by a second dose four weeks later, and then maintenance doses every eight weeks. However, the GUIDE trial was designed to explore whether extending the dosing interval from eight weeks to 16 weeks could provide similar efficacy while potentially improving convenience and reducing the treatment burden on patients.

Here's a review of that trial and its findings.

Study Design

The GUIDE trial was a randomized, double-blind, placebo-controlled, phase 3 study conducted across 80 centers in Germany and France. It enrolled adult patients with moderate-to-severe plaque psoriasis, characterized by a Psoriasis Area and Severity Index (PASI) score of 12 or higher and at least 10 percent of their body surface area affected by psoriasis.

Participants were randomized into three groups:

1. Guselkumab 8-Week Group: Patients received guselkumab at the standard dosing regimen of every eight weeks after the initial two doses.
2. Guselkumab 16-Week Group: Patients received guselkumab every 16 weeks after the initial two doses.
3. Placebo Group: Patients received placebo injections to serve as a control group.

The primary endpoints of the study were the proportion of patients achieving a PASI 90 response (indicating a 90 percent improvement in their psoriasis) and a Physician Global Assessment (PGA) score of 0 or 1, both of which reflect clear or almost clear skin.

In the first phase of the study (weeks 0-28), all participants received guselkumab 100 mg at weeks 0, 4, 12, and 20. Patients who achieved a PASI score of 0 at both weeks 20 and 28 were classified as super responders.

In the second phase (weeks 28-68), these super responders were then randomized to receive guselkumab every 8 weeks or every 16 weeks. Those who did not achieve super responder status continued with open-label guselkumab every 8 weeks.

Results

The results of the GUIDE trial demonstrated that guselkumab is highly effective in treating moderate-to-severe plaque psoriasis. Patients in both the 8-week and 16-week dosing groups showed significantly higher PASI 90 response rates compared to the placebo group, as shown below:

• 8-Week Dosing: The standard 8-week dosing regimen resulted in a high proportion of patients achieving and maintaining a PASI 90 response throughout the study period. Additionally, a substantial percentage of patients also achieved complete skin clearance (PASI 100), underscoring the efficacy of this regimen.
• 16-Week Dosing: The extended 16-week dosing interval was also effective, though to a slightly lesser degree than the 8-week regimen. A notable proportion of patients in this group still achieved PASI 90 and PGA 0/1 responses, although the percentages were somewhat lower compared to the 8-week group. Importantly, the 16-week regimen was particularly beneficial for patients who preferred less frequent injections and had challenges adhering to a more frequent dosing schedule.

Conclusion

The GUIDE randomized clinical trial provides robust evidence supporting the efficacy and safety of both 8-week and 16-week dosing regimens of guselkumab for the treatment of moderate-to-severe plaque psoriasis. While the 8-week regimen remains the gold standard for maximal efficacy, the 16-week regimen offers a viable alternative for patients seeking a less frequent dosing schedule with only a slight reduction in efficacy.

These findings also underscore the importance of individualized treatment approaches in managing chronic conditions like psoriasis, where patient preference and quality of life play crucial roles in therapeutic decision-making.

References:

Eyerich K, Asadullah K, Pinter A, et al. Noninferiority of 16-Week vs 8-Week Guselkumab Dosing in Super Responders for Maintaining Control of Psoriasis: The GUIDE Randomized Clinical Trial. JAMA Dermatology. Published online July 31, 2024. doi:https://doi.org/10.1001/jamadermatol.2024.2463

Maddi. Extended Guselkumab Dosing Proven Effective for Psoriasis. Dermatology Times. Published August 7, 2024. Accessed August 9, 2024. https://www.dermatologytimes.com/view/extended-guselkumab-dosing-proven-effective-for-psoriasis

Steinzor P. Extended Guselkumab Dosing Every 16 Weeks Proven Effective for Psoriasis Maintenance. AJMC. Published August 6, 2024. Accessed August 9, 2024. https://www.ajmc.com/view/extended-guselkumab-dosing-every-16-weeks-proven-effective-for-psoriasis-maintenance