Guselkumab Demonstrates Rapid and Lasting Results in Crohn Disease

Guselkumab delivered subcutaneously showed strong and sustained benefits in achieving both clinical remission and endoscopic response, without added safety concerns, in adults with moderate to severe Crohn disease, according to new data.1

The data, collected through a phase 3 double-blind, placebo-controlled, treat-through GRAVITI study (NCT05197049), helps to clarify support the May 2025 approval of subcutaneous guselkumab (Tremfya; Johnson & Johnson) for Crohn disease. | Image credit: New Africa - stock.adobe.com

The data, collected through a phase 3 double-blind, placebo-controlled, treat-through GRAVITI study (NCT05197049), help to support the May 2025 approval of subcutaneous guselkumab (Tremfya; Johnson & Johnson) for Crohn disease.1,2 The study was conducted to address the ongoing need for more effective, safer, and more convenient treatment options for Crohn disease by evaluating whether a fully subcutaneous guselkumab regimen, reducing the need for intravenous induction, could offer a patient-friendly alternative without compromising efficacy or safety.1

Adults aged 18 or older with active disease confirmed by radiologic, histologic, or endoscopic criteria and meeting specific symptom severity thresholds (eg, Crohn Disease Activity Index [CDAI] score between 220-450, stool frequency, and abdominal pain) were eligible for inclusion. All participants also needed to have endoscopic evidence of active disease with ulceration and must have failed or been intolerant to conventional or biologic treatments, though prior exposure to interleukin (IL)-12/23 or IL-23 inhibitors excluded them.

Patients were randomized in a 1:1:1 ratio to receive guselkumab at different dosing regimens or placebo, with stratification based on baseline disease severity and biologic failure status. Blinding was maintained through matched placebo injections and sham rescue procedures.

Participants were followed through a 48-week blinded period, during which clinical, endoscopic, biomarker, quality-of-life, and safety data were collected. The primary efficacy end points were clinical remission (CDAI < 150) and endoscopic response (Simple Endoscopic Score for Crohn’s Disease [SES-CD] reduction ≥ 50%) at week 12, with additional outcomes measured through week 48, including biomarker changes, endoscopic remission, and patient-reported outcomes.

In a study of 347 participants with moderate to severe Crohn disease, patients were randomized to receive guselkumab 400 mg SC followed by either 100 mg every 8 weeks, 200 mg every 4 weeks, or placebo. By week 16, more placebo patients (37.6%) required rescue treatment compared with guselkumab groups (12.2%), and early discontinuation was more common with placebo (10.3% vs 1.3%). By week 48, treatment discontinuation remained highest in the placebo group (26.5%) vs guselkumab groups (4.3%-15.3%).

Baseline demographics were similar across groups: 58.5% male, mean age 37.5 years, disease duration 8 years. About 46.4% had prior biologic failure, mostly anti-TNF, while 46.4% were bionaive. Most had elevated C-reactive protein levels (54.8%) and fecal calprotectin (71.7%).

At week 12, guselkumab showed significantly higher clinical remission (56.1% vs 21.4%), endoscopic response (41.3% vs 21.4%), and remission according to patient-reported outcomes (49.1% vs 17.1%) compared with placebo (P < .001 for all). These improvements continued through week 48, with clinical remission of 60.0% to 66.1% and endoscopic response of 44.3% to 51.3% in guselkumab groups vs 17.1% and 6.8% with placebo, respectively (P < .001). Endoscopic remission and deep remission were also significantly higher in both guselkumab groups.

“In conclusion, SC induction followed by SC maintenance treatment with guselkumab resulted in superior clinical and endoscopic improvements in participants with moderately to severely active Crohn’s disease through 48 weeks compared with placebo,” the authors concluded.

References

1. Hart A. Panaccione R, Steinwurz F, et al. Efficacy and safety of guselkumab subcutaneous induction and maintenance in participants with moderately to severely active Crohn’s disease: results from the phase 3 GRAVITI study. Gastroenterology. Published online March 18, 2025. doi:10.1053/j.gastro.2025.02.033

2. Santoro C. FDA approves guselkumab for adult patients with Crohn disease. March 21, 2025. Accessed May 22, 2025. https://www.ajmc.com/view/fda-approves-guselkumab-for-adult-patients-with-crohn-disease