麻豆传媒

Response-guided maintenance treatment for psoriasis allowed patients with exceptional early responses to double the treatment interval with guselkumab (Tremfya) with no loss in disease control, a randomized trial showed.

More than 90% of patients had a psoriasis area and severity index (PASI) score <3 at 68 weeks regardless of whether they received the interleukin (IL)-23 inhibitor every 8 or 16 weeks. Clinical signs and symptoms declined in parallel to immunologic changes, and skin CD8+ tissue-resident memory T (TRM)-cell count decreased quickly in both treatment groups. Laboratory studies showed that levels of inflammatory cytokines decreased significantly regardless of dosing interval.

Overall, more than a third of 822 patients enrolled in the GUIDE trial met criteria for super responders and qualified for the randomized phase comparing the two dosing intervals, reported Kilian Eyerich, MD, of the University of Freiburg in Germany, and colleagues in .

"Psoriasis treatment guidelines lack or provide inconsistent advice on patient stratification and treatment de-escalation," the authors noted. "We present the first randomized trial providing evidence that, in patients with early complete skin clearance at two consecutive visits ... extending the guselkumab dosing interval may control disease activity."

"Of note, disease control in the GUIDE trial was defined as PASI lower than 3, similar to treat-to-target goals proposed by national treatment guidelines," they added.

The results are consistent with those of the study, which showed that about a fourth of patients could extend the dosing interval for ustekinumab (Stelara) from 12 to 24 weeks with no loss in disease control, noted authors of an .

In the GUIDE trial, "among these super responders, 69% maintained a PASI score of 0 (or clear skin) with a dosing interval of 16 weeks compared to 81% of patients receiving guselkumab every 8 weeks," stated Andrew Blauvelt, MD, of Blauvelt Consulting in Lake Oswego, Oregon, and colleagues. "In other words, most patients achieving clear skin at week 28 do not need to continue on regular dosing. Injections can be spaced out in these patients deemed super responders, resulting in half as many injections over time, without losing efficacy."

The study of immunologic effects added key information to the primary findings.

"[The investigators] found that CD8+ TRM decreased rapidly following guselkumab treatment and remained low in patients treated with maintenance dosing either every 8 weeks or every 16 weeks," Blauvelt's group added. "Indeed, understanding drug effects of TRM is important, and decreased TRM cells have been shown to be a feature of drugs with long-term remission rates following withdrawal."

Eyerich and co-authors reported findings from the second part of the . The overall objective was to stratify patients with moderate/severe psoriasis on the basis of early and complete skin clearance (PASI 0) at two consecutive visits, weeks 20 and 28, with standard dosing at 8-week intervals. Deemed super responders, patients who met the criteria continued to a randomized phase, wherein they received guselkumab every 8 or 16 weeks and were followed to week 68. Patients who required retreatment in part two will be followed to week 220 in a .

During the initial treatment phase, 297 (36.1%) patients had PASI 0 scores at weeks 20 and 28 and were randomized to continue treatment with 8- or 16-week dosing intervals. The primary objective was to demonstrate the non-inferiority (with a 10% margin) of 16-week dosing with respect to maintaining psoriasis control (PASI <3) at week 68.

The primary results showed that 91.9% of patients randomized to 16-week dosing had PASI <3 at 68 weeks as compared with 92.6% with 8-week dosing (P<0.001 for non-inferiority).

Cytokine levels and skin effector T-cell subsets were exploratory analyses. Guselkumab treatment was associated with decreased serum levels of IL-17A, IL-17F, IL-22, and B Defensin-2 from baseline to week 28 and was maintained to week 68 in patients randomized to 8- or 16-week dosing.

CD8+ TRM count was elevated in lesional versus nonlesional skin at baseline and decreased to week 28 with guselkumab treatment. The effect was maintained through week 28, regardless of dosing interval, the authors reported.

About 70% of patients in each group had one or more adverse events, the most common of which were nasopharyngitis (15-18%) and headache (5-6%).

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