‘Promise of lasting efficacy’: Guselkumab outperforms placebo, ustekinumab in Crohn’s
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Key takeaways:
- Guselkumab achieved primary and secondary endpoints in patients with Crohn’s disease.
- However, clinical remission at week 48 was not statistically significant when compared with ustekinumab.
WASHINGTON — In patients with active Crohn’s disease, guselkumab was superior to both placebo and standard-of-care ustekinumab after 48 weeks of treatment, according to late-breaking data from the phase 3 GALAXI program.
“When we think about developing new therapies, we need to reflect on what are goals should be for our patients,” Remo Panaccione, MD, professor of medicine and director of the Inflammatory Bowel Disease Unit at the University of Calgary, told Healio. “The ultimate goal of treatment is to heal the bowel so that patients may achieve sustained clinical remission. New therapies need to build on and exceed on current standard of care. Treatments must be able to deliver improvements on the current standard of care in order to have the most impact on patients’ lives.”
Induction with IV guselkumab (Tremfya, Janssen) followed by subcutaneous maintenance therapy was safe and demonstrated efficacy in patients with CD based on results from the phase 2 GALAXI 1 trial, Panaccione said at Digestive Disease Week, where he presented week 48 results from the phase 3 GALAXI 2 and 3 trials.
“The purpose of this program was to investigate the use of guselkumab, a novel anti-IL-23 therapy with dual action, and compare its efficacy and safety not only with placebo but also against the standard of care, ustekinumab,” he told Healio.
Guselkumab vs. placebo, ustekinumab
In a double-blind, treat-through design, Panaccione and colleagues enrolled more than 1,000 patients (GALAXI 2, n = 508; GALAXI 3, n = 513) with moderately to severely active CD who had inadequate response or intolerance to conventional or biologic therapy.
Participants were randomly assigned 2:2:2:1 to one of four protocols: IV guselkumab 200 mg every 4 weeks with a transition at week 12 or 16 to subcutaneous 200 mg every 4 weeks or 100 mg every 8 weeks, respectively; IV ustekinumab (Stelara, Janssen) followed by subcutaneous 90 mg every 8 weeks starting at week 8; or placebo. Baseline demographics and disease characteristics were generally balanced among groups.
The composite coprimary endpoints independently assessed in the two trials included clinical response at week 12 and clinical remission at week 48 and clinical response and endoscopic response at week 48. Secondary endpoints included clinical remission and endoscopic response at week 12 between guselkumab and placebo, and endoscopic response and remission, clinical remission and endoscopic response, and deep and clinical remission at week 48 between guselkumab and ustekinumab.
Guselkumab superior in all but one endpoint
After one dose of IV guselkumab, Panaccione noted a “rapid response,” with approximately 40% of patients experiencing at least a 100-point drop in Crohn’s Disease Activity Index (CDAI) score or achieving a CDAI of less than 150, which was sustained with subsequent dosing to week 12. Additionally, clinical remission at week 12 was achieved by nearly 50% of patients who received guselkumab vs. placebo in both trials, and approximately 40% of patients achieved endoscopic response.
For the first composite coprimary endpoint, approximately 50% of patients in both guselkumab groups and trials achieved clinical response at week 12 and remission at week 48 vs. placebo. Of those who achieved clinical remission at week 48, 93% to 97% were in corticosteroid-free remission for at least 90 days before the 48-week endpoint, Panaccione said.
Similarly, approximately 40% of patients in both guselkumab groups and trials achieved the second coprimary endpoint of clinical response at week 12 and endoscopic response at week 48.
In a prespecified pooled analysis of the GALAXI 2 and 3 trials, the subcutaneous guselkumab doses were “statistically superior to ustekinumab” in endoscopic response, Panaccione told attendees, with nearly 50% of patients in the guselkumab groups achieving the endpoint. Endoscopic remission ranged from 30% to 37% and also was statistically significant vs. ustekinumab.
In addition, Panaccione noted clinical remission and endoscopic response at week 48 were statistically significant for guselkumab vs. ustekinumab (41.6% and 47.3% vs. 33.7%). About one-third of patients achieved a statistically significant difference in deep remission vs. ustekinumab (29.7% and 33.8% vs. 22.3%).
However, clinical remission at week 48 was not statistically significant between the guselkumab doses and ustekinumab, as all groups achieved high rates (65.4% and 70.3% vs. 62.9%).
Guselkumab ‘raising the bar’
According to Panaccione, guselkumab and ustekinumab were well-tolerated. The five most frequent adverse events reported with guselkumab were COVID-19, upper respiratory tract infection, worsening of CD, arthralgia and headache.
“When it comes to treating Crohn’s disease, mucosal healing and remission are key focus areas,” Panaccione told Healio, noting the results of the GALAXI program “bring us one step closer to raising the bar in our ability to reach these goals and with that a promise for lasting efficacy in IBD with options that suit the patient’s needs.”
He added: “With many therapies available for patients with moderately to severely active Crohn’s disease, our colleagues often ask what therapies they should use first or second. In the absence of head-to-head trials, the answer may be difficult. However, with the GALAXI program, given the rigor of the trial design, the breadth of the patient population studied, the robustness of the endpoints and the comparison to ustekinumab, guselkumab has the ability to reach our toughest goals and transform patient lives. It should be considered as a preferred first-line advanced therapy when it becomes available.”
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Panaccione R, et al. Efficacy and safety of guselkumab therapy in patients with moderately to severely active Crohn’s disease: Results of the GALAXI 2 & 3 phase 3 studies. Presented at: Digestive Disease Week; May 18-21, 2024; Washington (hybrid).
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