⚡First 4-in-1 psoriasis trial in high impact sites

Good morning — it’s Saturday, September 6, and we’re covering the first trial of a biologic across four high-impact sites in low body surface area psoriasis, new data on rademikibart in atopic dermatitis, and more.

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The Phase 3b SPECTREM trial, published in the BJD, found guselkumab highly effective in patients with low body surface area psoriasis affecting high-impact sites (scalp, face, genitals, and intertriginous areas).

Most psoriasis involves a low body surface area. High-impact sites are also often involved, impair quality of life, and leave over 90% of patients with persistent symptoms despite topical therapy.

Investigators randomized 338 adults with moderate psoriasis involving 2–15% body surface area and at least one high-impact site to guselkumab or placebo. All patients had an inadequate response or intolerance to prior topical therapy.

The mean baseline DLQI was 12 (range 0–30), indicating a very large effect on quality of life despite treatment.

At Week 16, 53% of guselkumab-treated patients reached ≥90% reduction in psoriasis severity (PASI 90), compared to 6% on placebo (P<0.0001).

Patients achieved high rates of clear or almost clear skin (IGA or PGA 0/1) at all major sites: scalp (75% vs 15%), intertriginous areas (87% vs 29%), face (88% vs 29%), and genital region (78% vs 38%) (all P<0.001).

Notably, nearly half of all guselkumab-treated patients reported no impact on quality of life (DLQI 0/1: 49% vs 4% on placebo).

Safety was consistent with guselkumab’s known profile, with no discontinuations due to adverse events.

SPECTREM is the first study to apply a ‘4-in-1’ design, delivering statistically powered results across all four high-impact psoriasis sites with greater efficiency.

> Rademikibart reduces disease severity in atopic dermatitis and maintains efficacy with extended dosing: The SEASIDE CHINA Phase 2 trial, published in the BJD, found that rademikibart was effective in moderate-to-severe atopic dermatitis, with responses sustained or further improved after switching from every 2 weeks to monthly dosing. Rademikibart is a next-generation IL-4Rα antibody engineered for stronger binding than dupilumab, potentially enabling longer dosing intervals. In Stage 1 of the trial, 330 patients were randomized to subcutaneous rademikibart every 2 weeks or placebo. At Week 16, 59% of rademikibart-treated patients achieved a ≥75% reduction in disease severity (EASI-75) vs 23% on placebo (P<0.001). Those who reached EASI-50 were then re-randomized in Stage 2 to continue dosing every 2 weeks or switch to every 4 weeks. By Week 52, EASI-75 rates rose from 69–74% at Week 16 to 85% in both groups. Most patients who had achieved EASI-75 at Week 16 maintained their response (90–92%). Safety was favorable, with low rates of conjunctivitis (6% vs 3% placebo) and keratitis (<1%). The authors noted efficacy appeared similar or greater than that of other IL-4/IL-13 inhibitors but cautioned against cross-trial comparisons.

> First real-world meta-analysis of JAK inhibitors in atopic dermatitis: A meta-analysis in Clinical & Experimental Allergy is the first to evaluate real-world efficacy–safety of oral JAK inhibitors in moderate-to-severe atopic dermatitis. The analysis assessed abrocitinib, baricitinib, and upadacitinib in 50 observational studies. Across cohorts, the proportion of patients achieving EASI-75 was 44% at Week 4, rising to 73% at Week 16 and 86% at Week 52. Upadacitinib often showed numerically higher EASI-75 and EASI-90 rates than abrocitinib or baricitinib. Acne was the most frequent adverse event (16%), followed by elevated creatine phosphokinase (13%) and lipids (12%). Other laboratory findings included anemia (4%) and elevated transaminases (3%). Infections such as herpes simplex (6%), herpes zoster (2%), and respiratory infections (6%) were also reported. Serious adverse events were rare, with single cases of cutaneous lymphoma and anal cancer, and two venous thromboembolic events. Limitations include the absence of active comparators, follow-up restricted to 52 weeks, and the small number of studies and participants at later timepoints, which may have introduced attrition bias from patient dropout. Real-world outcomes with JAK inhibitors appear consistent with those seen in clinical trials.

> Bermekimab fails Phase 2 trial in hidradenitis suppurativa: Bermekimab, an anti–IL-1α monoclonal antibody, failed to show efficacy in a Phase 2 trial of adults with moderate–to–severe hidradenitis suppurativa. The study was terminated early after a futility analysis of the first 75 patients indicated lack of benefit. Investigators randomized 151 participants to bermekimab, adalimumab, or placebo, with placebo patients crossing over to bermekimab after Week 16. The primary endpoint was HiSCR50, defined as ≥50% reduction in abscess and nodule counts with no increase in abscesses or draining tunnels. In the Week 16 modified analysis, HiSCR50 was achieved by 37% of patients on placebo and 37% on bermekimab. Adalimumab had a higher response (57%), consistent with prior hidradenitis suppurativa trials, and also reduced inflammatory nodules and pain. Bermekimab was generally well tolerated, though treatment-emergent adverse events occurred more often than with placebo. While earlier small studies of bermekimab suggested benefit, these results do not support further development in hidradenitis suppurativa, marking a setback for a disease with few effective therapies.

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