New data from clinical trials indicate that guselkumab (Tremfya; Johnson & Johnson), an interleukin-23 (IL-23) inhibitor, is effective in treating plaque psoriasis affecting specific, often overlooked areas and in managing Crohn's disease. The phase 3b SPECTREM trial (NCT06039189) and phase 3 GRAVITI study (NCT05197049) highlight the drug's potential in addressing unmet needs in these conditions.
SPECTREM Trial: Guselkumab for Plaque Psoriasis in Special Sites
The SPECTREM trial, a prospective, large-scale, randomized-controlled study, evaluated guselkumab's efficacy in adults with moderate plaque psoriasis affecting sensitive or highly visible areas such as the face, scalp, skin folds, and genitals. These "special sites" often significantly impact patients' daily lives but are frequently undertreated. The primary endpoint was achieving an Investigator’s Global Assessment (IGA) score of 0 (cleared) or 1 (minimal disease) at week 16, compared to placebo.
The results showed that a significantly greater proportion of patients receiving guselkumab achieved optimal IGA scores (74.2%) compared to those on placebo (12.4%). Improvements were observed across all special sites, including the scalp (75.0% versus 14.5%), face (87.8% versus 28.6%), intertriginous areas (86.5% versus 28.8%), and genitals (78.0% versus 37.5%).
Linda Stein Gold, MD, a SPECTREM investigator, noted, "People who have special site plaque psoriasis with lesions that cover a smaller total area of their body are often only prescribed topical treatments and not considered candidates for advanced therapies, as treatment decisions are often driven by body surface area coverage and not symptomatic burden. Results of the SPECTREM study could represent a new approach to care for patients with low body surface area psoriasis."
GRAVITI Study: Guselkumab in Crohn's Disease
The GRAVITI study assessed the effects of subcutaneous induction and maintenance therapy with guselkumab in adults with moderately to severely active Crohn's disease. At the American College of Gastroenterology 2024 meeting, researchers presented data showing that over half of patients treated with guselkumab 400 mg (administered subcutaneously at weeks 0, 4, and 8) achieved clinical remission (56.1%) compared with those receiving placebo (21.4%). An endoscopic response was achieved in 41.3% of patients treated with guselkumab SC induction therapy, compared with 21.4% in the placebo group. Notably, improvements in clinical remission were seen as early as week 4 in some patients.
Longer-term follow-up data at week 48 revealed that clinical remission rates were more than three times higher with both maintenance doses of guselkumab versus placebo (60.0% for 100 mg SC every 8 weeks, 66.1% for 200 mg SC every 4 weeks, vs 17.1%). A robust endoscopic response was also observed in patients receiving both 100 mg and 200 mg guselkumab.
Implications of the Findings
These trial results follow guselkumab’s regulatory approval by the FDA for the treatment of moderate-to-severe ulcerative colitis in September 2024. The positive outcomes from the SPECTREM and GRAVITI studies suggest that guselkumab may soon be considered for regulatory approval to treat other conditions, including Crohn's disease and plaque psoriasis.
