Tremfya Achieves Significant Clinical Remission, Endoscopic Response in Moderate to Severe Crohn Disease at 48 Weeks

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Patients with moderate to severe Crohn disease (CD) administered treatment with subcutaneous (SC) Tremfya (guselkumab) achieved clinically significant remission and endoscopic response at 48 weeks, according to results from the Phase III GRAVITI trial (NCT05197049).^1,2 These findings, presented at the American College of Gastroenterology 2024 Annual Scientific Meeting, follow data released earlier this month from the Phase III GALAXI trial (NCT03466411) and the Phase III QUASAR maintenance trial (NCT04033445), which show that Tremfya produced high rates of endoscopic remission in patients with CD and ulcerative colitis (UC).³

“The GRAVITI results show that induction treatment with subcutaneous guselkumab is as rapid and robust as we have seen with the IV induction, which could offer a welcome new option for Crohn’s disease treatment,” study investigator Remo Panaccione, MD, FRCPC, professor of Medicine and director of the Inflammatory Bowel Disease Unit at the University of Calgary, said in a press release. “The one-year results of this study suggest that SC induction with guselkumab is a promising approach to help people with CD manage their symptoms and achieve meaningful endoscopic improvements.”¹

Tremfya was the first FDA-approved, fully-human, dual-acting monoclonal antibody to block interleukin (IL)-23—a significant driver of the pathogenesis of inflammatory diseases—by attaching to the p19 subunit of IL-23 and to CD64, a receptor on cells that produce IL-23. Tremfya is currently indicated to treat adult patients with moderate to severe plaque psoriasis who may benefit from systemic therapy or phototherapy; for adult patients with active psoriatic arthritis; and most recently for adult patients with moderately to severely active ulcerative colitis.⁴

The randomized, double-blind, placebo-controlled GRAVITI trial analyzed SC Tremfya induction treatment at a dose of 400 mg at weeks zero, four, and eight in patients with moderately to severely active CD who did achieve an adequate response or who failed to tolerate conventional therapy with corticosteroids or immunomodulators, or biologic therapy with tumor necrosis factor antagonists or Entyvio (vedolizumab).

Patients were administered SC Tremfya 400 mg every four weeks (q4w) followed by SC Tremfya 200 mg q4w; or SC Tremfya 400 mg q4w followed by Tremfya 100 mg SC every eight weeks (q8w); or placebo. The GRAVITI trial used a treat-through design similar to the GALAXI trial. In this design, patients were randomly assigned to receive Tremfya at week zero and remain on the regimen for the duration of the trial, regardless of the clinical response status achieved at the end of induction. Those randomly assigned to the placebo cohort were eligible to switch to SC Tremfya if rescue criteria were met at week 16.

Results from the 12-week induction period show that 56.1% of patients in the Tremfya cohort achieved clinical remission compared with 21.4% of patients administered placebo. An endoscopic response was achieved by 41.3% of patients in the Tremfya cohort compared with 21.4% of patients in the placebo cohort. Investigators noted a rapid onset of action with Tremfya, as greater improvements in clinical remission were observed as early as week four in this cohort.

Results from the 48-week induction period show rates of clinical remission with maintenance doses of SC Tremfya at 60.0% for 100 mg q8w and 66.1% for 200 mg q4w compared with 17.1% with placebo. Endoscopic response was achieved by 44.3% of patients with SC Tremfya 100 mg q8w and 51.3% for 200 mg q4w compared with 6.8% in the placebo cohort. Endoscopic remission was achieved by 30.4% of patients administered SC Tremfya 100 mg q8w and 38.3% of administered 200 mg q4w group compared with 6.0% in the placebo cohort.

In terms of safety, the results were consistent with prior trials of Tremfya and no new signals were reported.

“These results show that Tremfya has the potential to become the only IL-23 inhibitor to offer both SC and IV induction options for Crohn’s disease, and, if approved, will offer choice and flexibility for people living with CD,” Esi Lamousé-Smith, MD, PhD, vice president, Gastroenterology Disease Area Lead, Immunology, Johnson & Johnson Innovative Medicine, said in a press release. “The convenience of self-administration from the start of treatment is part of our commitment to delivering innovative therapeutic solutions to people with Crohn’s disease.”¹

References

1. TREMFYA® (guselkumab) is the first and only IL-23 inhibitor to demonstrate robust results with a fully subcutaneous regimen in both induction and maintenance in Crohn’s disease. News release. Johnson & Johnson. October 28, 2024. Accessed October 29, 2024. https://www.jnj.com/media-center/press-releases/tremfya-guselkumab-is-the-first-and-only-il-23-inhibitor-to-demonstrate-robust-results-with-a-fully-subcutaneous-regimen-in-both-induction-and-maintenance-in-crohns-disease

2. A Study of Guselkumab Subcutaneous Therapy in Participants With Moderately to Severely Active Crohn's Disease (GRAVITI). ClinicalTrials.gov. Updated October 29, 2024. Accessed October 29, 2024. https://clinicaltrials.gov/study/NCT05197049

3. TREMFYA® (guselkumab) demonstrates impressive results across biologic-naïve and biologic-refractory patients in Crohn’s disease and ulcerative colitis. News release. Johnson & Johnson. October 10, 2024. Accessed October 29, 2024. https://www.jnj.com/media-center/press-releases/tremfya-guselkumab-demonstrates-impressive-results-across-biologic-naive-and-biologic-refractory-patients-in-crohns-disease-and-ulcerative-colitis.

4. TREMFYA® (guselkumab) receives U.S. FDA approval for adults with moderately to severely active ulcerative colitis, strengthening Johnson & Johnson’s leadership in inflammatory bowel disease. J&J. September 11, 2024. Accessed October 29, 2024. https://www.jnj.com/media-center/press-releases/tremfya-guselkumab-receives-u-s-fda-approval-for-adults-with-moderately-to-severely-active-ulcerative-colitis-strengthening-johnson-johnsons-leadership-in-inflammatory-bowel-disease