Guselkumab shows promise against Crohn’s disease

Guselkumab, a selective p19 interleukin-23 antagonist, induces better 12-week clinical and endoscopic improvements relative to placebo without triggering alarming side effects, reports a new phase II trial.

The double-blinded study randomized 309 Crohn’s disease patients 1:1:1:1 to receive 200-, 600-, or 1,200-mg intravenous guselkumab, or a placebo control, at weeks 0, 4, and 8. Concomitantly, participants received around 6 mg/kg of subcutaneous ustekinumab at week 0, followed by a 90-mg dose at week 8.

The main outcome of interest was the change in Crohn’s Disease Activity Index (CDAI) score from baseline. Other endpoints included clinical remission, clinical-biomarker response, endoscopic response, Patient Reported Outcomes-2 (PRO-2)-defined remission, and safety profile.

At week 12, least-squares mean reductions in baseline CDAI were significantly greater in the 200-, 600-, and 1,200-mg guselkumab doses relative to placebo (–160.4, –138.9, and –144.9 vs –36.2, respectively; p<0.05 for all comparisons).

Similarly, more than half (53.0 percent; n=98 of 185) of patients in the combined guselkumab group achieved clinical remission, as opposed to only 16.4 percent (n=10 of 61) in the placebo group (p<0.05). The same was true for clinical response, PRO-2 remission, and clinical-biomarker response. Notably, 12-week endoscopic response was likewise significantly higher in the combined guselkumab vs placebo group (35.7 percent vs 11.5 percent; nominal p<0.05).

In terms of safety, the proportion of patients developing at least one adverse event (AE) was comparable across all treatment groups. The researchers also reported no apparent link between guselkumab dose and AE incidence. All arms likewise showed low rates of serious AEs and discontinuation due to AEs.