Intravenous induction followed by subcutaneous maintenance therapy with guselkumab improved clinical and endoscopic outcomes in adults with moderately to severely active Crohn’s disease at 48 weeks, according to results from two phase 3 trials.
The combined analysis included 1021 participants from GALAXI-2 and GALAXI-3—randomized, double-blind, placebo- and active-controlled trials conducted at 257 sites across 40 countries. Participants were randomly assigned to receive guselkumab 200 mg, guselkumab 100 mg, ustekinumab, or placebo. All had Crohn’s disease for more than 3 months with endoscopic disease confirmed by SES-CD criteria.
The two coprimary composite endpoints were clinical response at week 12 and either clinical remission or endoscopic response at week 48. Clinical response was defined as a decrease of at least 100 points in the Crohn’s Disease Activity Index (CDAI) or a CDAI score less than 150.
In GALAXI-2, 54.8% (80/146) and 49.0% (70/143) of participants in the 200 mg and 100 mg guselkumab groups, respectively, met the response/remission endpoint, compared with 11.8% (9/76) in the placebo group. In GALAXI-3, these proportions were 48.0% (72/150) and 46.9% (67/143), versus 12.5% (9/72) for placebo.
For clinical response and endoscopic response, guselkumab again showed superiority. In GALAXI-2, 38.4% (56/146) and 39.2% (56/143) in the respective guselkumab groups achieved this outcome, compared with 5.3% (4/76) in the placebo group. In GALAXI-3, results were 36.0% (54/150) and 33.6% (48/143), versus 5.6% (4/72) for placebo.
Most participants who achieved clinical remission at week 48 were also corticosteroid-free for more than 90 days. This included 92.5% and 95.7% in the 200 mg and 100 mg groups, respectively, in GALAXI-2, and 93.1% and 97.0%, respectively, in GALAXI-3.
In prespecified head-to-head analyses, both guselkumab regimens were superior to ustekinumab for all endoscopic endpoints, including endoscopic response, endoscopic remission, and deep remission. However, no significant difference was observed between guselkumab and ustekinumab for clinical remission alone at week 48.
Serious adverse events occurred in 7.1% of participants in the guselkumab 200 mg group, 11.2% in the 100 mg group, 12.0% in the ustekinumab group, and 15.0% in the placebo group. No deaths were reported.
Subgroup analyses showed consistent efficacy among both biologic-naive patients and those with prior inadequate response or intolerance to biologics. Clinical benefit was observed as early as week 4 following the first intravenous dose.
Guselkumab demonstrated sustained efficacy and a favorable safety profile through 48 weeks in adults with moderately to severely active Crohn’s disease.
Full disclosures can be found in the published study.
Source: The Lancet