GUIDE: Guselkumab Dosing Every 16 Weeks Maintains Psoriasis Control

Results from the GUIDE clinical trial showed that an extended dosing interval of guselkumab was effective for the treatment of moderate-to-sever plaque psoriasis.

"Psoriasis is a chronic, systemic immune-mediated disease, predominately characterized by skin plaques, "the researchers wrote in JAMA Dermatology. "Owing to the chronic and often progressive nature of the disease, long-term treatment is required, and the timing of targeted intervention plays a crucial role in the ensuing response to therapy. Though treatment de-escalation of biologic therapies for psoriasis is commonly applied in daily practice, evidence-based treatment guidelines and algorithms are lacking."

The phase 3b, randomized, double-blinded, controlled trial, focused on a specific subset of patients termed "super responders" (SRes) and included 822 patients (of whom 297 were classified as SRes). SRes patients achieved a Psoriasis Area and Severity Index (PASI) score of 0 at two consecutive visits (weeks 20 and 28), indicating complete skin clearance. Patients were randomized to receive guselkumab either every eight weeks or every 16 weeks.

According to the researchers, the primary endpoint of interest was met, with 91.9% of patients in the 16-week group and 92.6% in the 8-week group maintaining PASI <3 at week 68, showing the noninferiority of the extended dosing regimen. Secondary outcomes also supported the primary findings, with high rates of PASI 75/90/100 achieved in both groups.  More than 81% of patients on the 8-week regimen and 69.1% on the 16-week regimen maintained a PASI of 0 at week 68. 

The authors also reported the immunological impact of guselkumab on tissue-resident memory T (TRM) cells implicated in the recurrence of psoriasis lesions. The results showed a sustained reduction of CD8-positive TRM cells in the lesional skin of SRes, regardless of dosing interval, supporting long-term disease control with extended dosing. Safety was acceptable, with a comparable incidence of treatment-emergent adverse events (TEAEs) across both dosing groups. The most common TEAEs included nasopharyngitis and headache, with no new safety signals identified.

"Data from the GUIDE trial add new insights into the concepts of disease modification and long-term maintenance of efficacy," the authors concluded. "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."

Source: Eyerich K. JAMA Dermatology. 2024. Doi:10.1001/jamadermatol.2024.2463