Guselkumab was associated with greater clinical and endoscopic improvements compared with placebo at week 12 in patients with Crohn disease, according to a study in Gastroenterology.

Investigators reported results from the induction portion of the phase 2, international, randomized, double-blind GALAXI-1 study (ClinicalTrials.gov Identifier: NCT03466411), which evaluated the efficacy and safety of guselkumab in patients with moderately to severely active Crohn disease.

Study participants were aged 18 years and older and had active Crohn disease for at least 3 months. The patients were randomly assigned 1:1:1:1:1 to receive intravenous (IV) guselkumab 200 mg, 600 mg, or 1200 mg at weeks 0, 4, and 8; ustekinumab approximately 6 mg/kg IV at week 0 and subcutaneous 90 mg at week 8; or placebo. The primary endpoint was the change in Crohn Disease Activity Index (CDAI) score at week 12.


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A total of 309 patients (mean age, 38.8±13.36 years; 59.2% men; mean disease duration, 8.8±8.70 years) were included in the primary efficacy analysis. In the combined guselkumab group, 54.6% of patients had an inadequate response or intolerance to prior biologic therapy and 45.4% to conventional therapy.

At week 12, the guselkumab 200-mg (-160.4), 600-mg (-138.9), and 1200-mg (-144.9) groups had significantly greater least squares mean reductions from baseline in CDAI score compared with the placebo group (-36.2); P <.05 for all comparisons. No apparent dose response was found among the doses.

In the combined guselkumab group, 53.0% of patients were in clinical remission compared with 16.4% in the placebo group (P <.05). In addition, 65.9% of patients in the combined guselkumab group and 24.6% of participants in the placebo group had a clinical response at week 12 (nominal P <.05).

In the combined guselkumab group at week 12, Patient Reported Outcome-2 remission and clinical biomarker response were achieved in 42.7% and 47.0% of patients, respectively, vs 16.4% and 6.6% of those in the placebo group, respectively (nominal P <.05). Endoscopic response was observed in 35.7% of participants in the combined guselkumab group and in 11.5% of those in the placebo group (nominal P <.05).

In a subgroup of patients who had an inadequate response or intolerance to previous biologic therapy, 47.5% of patients in the combined guselkumab group and 10.0% of those in the placebo group had clinical remission at week 12.

The investigators observed no exposure-response between systemic guselkumab exposure and change in CDAI, clinical remission, or endoscopic response at week 12. Among 360 patients in the safety analysis group, the rates of those with 1 or more adverse events were similar among the treatment groups (placebo, 60.0%; combined guselkumab, 45.7%; and ustekinumab, 50.7%).

Among several limitations, the results are based on a limited number of patients who received 12 weeks of induction therapy. Also, ustekinumab was used as a reference arm, and the study was not designed to compare the 2 agents with adequate statistical power.

“IL-23p19 inhibition with guselkumab resulted in clinical and endoscopic improvement in Crohn disease patients with an inadequate response or intolerance to prior conventional or biologic therapy supporting initiation of pivotal induction and maintenance studies in Crohn disease,” the investigators stated.

Disclosure: This research was supported by Janssen Research & Development, LLC. Please see the original reference for a full list of disclosures.

Reference

Sandborn WJ, D’Haens GR, Reinisch W, et al. Guselkumab for the treatment of Crohn’s disease: induction results from the phase 2 GALAXI-1 study. Gastroenterology. Published online February 5, 2022. doi: 10.1053/j.gastro.2022.01.047