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The selective p19 interleukin (IL)-23 blocker guselkumab (Tremfya) was safe and reduced disease activity in adults with moderate to severe Crohn's disease who had an inadequate response to prior therapies, a randomized phase II trial found.

For the primary endpoint in GALAXI-1, three dose levels of intravenous guselkumab each demonstrated significantly greater reductions in Crohn's disease activity index (CDAI) scores at week 12 versus placebo (P<0.05 for all), with a least squares (LS) mean change from baseline of:

• -160.4 with guselkumab 200 mg
• -138.9 with guselkumab 600 mg
• -144.9 with guselkumab 1,200 mg
• -36.2 with placebo

At this time point, clinical remissions -- CDAI below 150 -- occurred more often with each of the three guselkumab doses (57.4%, 55.6%, 45.9%, respectively) than with placebo (16.4%; P<0.05 for all), reported William Sandborn, MD, of the University of California San Diego, and colleagues.

"All three doses of guselkumab evaluated induced clinically meaningful improvements in patients with moderately to severely active Crohn's disease, with a favorable safety profile," the group wrote in .

When looking at the guselkumab groups combined, more of these patients achieved clinical response, clinical-biomarker response, endoscopic response, and patient-reported remissions compared with the placebo group (P<0.05 for all):

• Clinical response: 65.9% vs 24.6%
• Clinical-biomarker response: 47% vs 6.6%
• Endoscopic response: 35.7% vs 11.5%
• Patient-reported remissions: 42.7% vs 16.4%

Conventional first-line Crohn's therapies such as methotrexate, corticosteroids, or thiopurines often fail at providing long-term clinical remission and have high toxicity, noted Sandborn and colleagues. Biologics can be beneficial, but lead to intolerance, treatment failure, and reduced long-term efficacy in severe disease.

Guselkumab selectively inhibits the p19 subunit of IL-23 and is an approved option in plaque psoriasis and psoriatic arthritis. In , sponsor Janssen said clinical remissions were observed in 65% of patients treated with guselkumab at week 48, and noted that phase III trials are currently enrolling.

was a five-arm, double-blind, phase II trial that randomized 360 adults with Crohn's disease to guselkumab doses of 200 mg, 600 mg, and 1,200 mg; a reference arm of ustekinumab (Stelara); or to placebo across 128 sites in 32 countries. Guselkumab was administered intravenously at baseline, week 4, and week 8. Overall, 309 patients were available for the efficacy analysis after 51 patients had their treatment paused following an event of hepatitis in a patient assigned to the 1,200 mg guselkumab arm.

A post-hoc analysis showed that ustekinumab -- an approved IL-12/23 blocker approved for Crohn's disease -- was superior to placebo at week 12.

Patients in the trial needed to have moderate to severe Crohn's disease with an "inadequate response or intolerance" to biologics or conventional therapies. Average follow-up was 12.2 weeks.

Average patient age was 39 years and their mean disease duration was 8.8 years. About three-fourths were on Crohn's medication at baseline: corticosteroids in 37%, immunomodulators in 36%. More than half (54%) had disease refractory to biologics.

For safety, 46% of the patients in the guselkumab groups experienced an adverse event (AE), as compared to 60% in the placebo group and 51% of the ustekinumab group. Common AEs included upper respiratory infections, abdominal pain, and arthralgia (each 6%). Rates of infection were low among groups (15%, 21%, and 13%, respectively), and there were no deaths in the trial.

Three serious AEs were observed with guselkumab -- viral gastroenteritis and enterovesical fistula in the 600 mg group, and anal abscess in the 200 mg group. One serious abdominal infection occurred in the ustekinumab group.

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