Study Highlights Guselkumab Effect on Psoriasis Patients with Early Skin Clearance

Disease activity among individuals with moderate to severe plaque psoriasis with early complete skin clearance can be controlled through an extended guselkumab dosing interval, according to recent findings.¹

The findings from the GUIDE randomized clinical trial represent the first to show that disease activity can be controlled following a dosing extension among those with early complete skin clearance. This research was led by Kilian Eyerich, MD, from the department of dermatology and venereology at the University of Freiburg Medical Center in Germany.

Eyerich and colleagues noted that guidelines for psoriasis therapy do not provide consistent counsel on patient stratification and de-escalation of treatment. GUIDE was conducted to allow for clinical and molecular insights into durable remission and modification of disease.²

“Herein, we present primary end point data, supported by other clinical and immunologic findings, to evaluate whether de-escalation of guselkumab treatment by dosing interval extension to every 16 weeks is noninferior to dosing every 8 weeks for maintaining clinical response in SRes,” Eyerich and colleagues wrote.¹

Study Design

There were 3 segments of the research team’s work: the assessment of early intervention, the prolonged dosing intervals, and the period of maintenance response following withdrawal from therapy. In GUIDE’s second part, the analysis described in this summary, the patient interactions took place from September 2019 - March 2022.

The investigators carried out this phase 3b, double-blind, randomized clinical trial across 80 centers located in Germany and France, seerking to evaluate guselkumab’s efficacy in terms of early intervention and extended dosing intervals. The drug itself is an IL-23 inhibitor which targets the p19 subunit among those with moderate to severe psoriasis.

Those who were participants in the first part of GUIDE, lasting from the 0 to 28-week mark, were given 100 mg of guselkumab at the 0, 4, 12, and 20-week marks. A classification was given to subjects who succeeded at reaching a Psoriasis Area and Severity Index (PASI) of 0 by the 20 and 28-week points, and this classification was ‘super responders’ (SRes).

In the second segment, lasting from the 28 to 68-week mark, those labeled as SRes were randomized to be treated with 100 mg either every 8 weeks or every 16 weeks. At the same time, those labeled as non-SRes would keep receiving guselkumab every 8 weeks on an open-label basis.

The conclusion that dosing guselkumab was not inferior in the maintenance of disease control on an every-16-week basis (within a 10% margin) versus every 8 weeks (PASI <3 at week 68) among subjects labeled as SRes was GUIDE’s primary aim. Biomarker substudies were also carried out to evaluate the immunologic impact of the therapy in both skin and blood.

Findings

Overall, there were 822 participants who had been treated with guselkumab in GUIDE’s second part. Among these individuals, 36.1% were labeled as SRes, with administration occurring every 8 weeks. A total of 63.9% were labeled as non-SRes, with treatment every 16 weeks.

Among the subjects featured in the SRes, the average age was noted as 39.4 years with 32.0% being labeled as female and 68.0% male. The research team reported that they had achieved the primary endpoint, finding the noninferiority of the drug administered every 16 weeks compared to every 8 weeks in SRes (P = .001).

The team also found at the 68-week mark that 91.9% (90% CI, 87.3%-95.3%) of SRes treated every 16 weeks and 92.6% (90% CI, 88.0%-95.8%) on the every-8-week treatment regimen reported a PASI score below 3. Such results aligned with immunologic shifts, given the rapid decrease in skin CD8-positive tissue-resident memory T (TRM) cells from baseline and that it had remained low in both dosing cohorts.

In a similar vein, serum levels of IL-17A, IL-17F, IL-22, and β-defensin 2 were shown to have dipped significantly from the point of baseline. Levels remained low through to the 68-week mark. They determined that guselkumab was well-tolerated among participants, adding that no new safety concerns had been seen.

“Future analyses from the GUIDE trial will assess the association between clinical response and biomarker and pharmacokinetic data, and further evaluate maintenance of long-term response after treatment withdrawal,” they wrote.

References

1. ^{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 Dermatol. Published online July 31, 2024. doi:10.1001/jamadermatol.2024.2463}
2. ^{Eyerich K, Weisenseel P, Pinter A, et al. IL-23 blockade with guselkumab potentially modifies psoriasis pathogenesis: rationale and study protocol of a phase 3b, randomised, double-blind, multicentre study in participants with moderate-to-severe plaque-type psoriasis (GUIDE). BMJ Open. 2021;11(9):e049822. doi:10.1136/bmjopen-2021-049822.}