Guselkumab de-escalation maintains psoriasis control in patients with early skin clearance

Key takeaways:

• Guselkumab dosing every 16 weeks was noninferior to dosing every 8 weeks for maintaining psoriasis disease control.
• From baseline, guselkumab treatment decreased psoriasis biomarkers in both dosing groups.

In patients with early and complete clearance of psoriasis, extending the guselkumab dosing interval to every 16 weeks maintained disease control as well as an 8-week interval, according to a study published in JAMA Dermatology.

Because long-term treatment is required for psoriasis, “the timing of targeted intervention plays a crucial role in the ensuing response to therapy,” Kilian Eyerich, MD, full professor and medical director in the department of dermatology at Medical Center, University of Freiburg in Germany, and colleagues wrote. “Though treatment de-escalation of biologic therapies for psoriasis is commonly applied in daily practice, evidence-based treatment guidelines and algorithms are lacking.”

The GUIDE clinical trial, an ongoing phase 3b, randomized, double-blinded, parallel group, multicenter study of treatment de-escalation among patients with moderate to severe plaque psoriasis, consists of three parts. The current analysis focuses on part 2 of the study,

which included 297 patients (mean age, 39.4 years; 68% men) with psoriasis who achieved PASI 0 at both week 20 and week 28 — indicating early and complete skin clearance — following the receipt of 100 mg guselkumab (Tremfya, Janssen) weeks 0, 4, 12 and 20 of part 1 of the study.

To evaluate the effect of prolonging the dosing interval for guselkumab, Eyerich and colleagues randomly assigned 149 of the patients to receive guselkumab 100 mg every 16 weeks (group 2b) and 148 to receive guselkumab 100 mg every 8 weeks (group 2a).

The primary endpoint of the study was the percentage of patients achieving absolute PASI lower than 3 at week 68 to demonstrate noninferiority of guselkumab dosing every 16 weeks vs. every 8 weeks regarding maintenance of disease control, according to the researchers. Researchers used a 10% margin to define noninferiority.

This endpoint was met (P = .001), with 91.9% (90% CI, 87.3%-95.3%) of patients from group 2b and 92.6% (90% CI, 88%-95.8%) of patients from group 2a achieving PASI lower than 3 at week 68 (OR = 0.92; 90% CI, 0.45-1.87).

Researchers also conducted exploratory substudies which showed that skin CD8-positive tissue-resident memory T-cell count continued to decrease from baseline with guselkumab treatment up to week 68 in both groups.

Additionally, guselkumab treatment decreased serum IL-17A, IL-17F, IL-22 and BD-2 levels from baseline to week 28, with these biomarkers remaining low in both dosing groups up to week 68.

The researchers noted that guselkumab was well tolerated and showed no new safety signals.

“Our current findings suggest that early intervention with guselkumab increases the likelihood of achieving super response and thus subsequently may be important to accommodate therapeutic strategies through dosing interval flexibility,” the researchers wrote. “The GUIDE clinical trial contributes critical prospective data to help address individual patient needs in everyday practice and potentially improve long-term disease management and patient compliance with treatment.

“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 added.