Guselkumab maintenance therapy achieved high efficacy rates in Crohn’s disease

Subcutaneous guselkumab maintenance therapy achieved high efficacy rates in participants with Crohn’s disease (CD) after 2 years of follow-up in the treat-through, phase 2 GALAXI-1 study. The safety profile was favourable in this population and consistent with the safety profile of guselkumab in approved indications. Phase 3 studies assessing guselkumab in CD are currently running.

The phase 2 GALAXI-1 trial (NCT03466411) randomised participants with moderately to severely active CD, who failed on prior conventional and/or biologic therapies, to 200 mg guselkumab, 600 mg guselkumab, 1,200 mg guselkumab, or placebo (intravenous, every 4 weeks). The results from the 12-week induction study demonstrated that guselkumab is associated with significantly improved clinical outcomes compared with placebo, according to Prof. Silvio Danese (Vita-Salute San Raffaele University, Italy) [1]. After week 12, participants in the 1,200 mg and 600 mg arms received 200 mg guselkumab, subcutaneous, every 4 weeks (n=61; n=63), whereas participants who were originally randomised to 200 mg guselkumab, received 100 mg guselkumab, subcutaneous, every 8 weeks (n=61). In addition, an ustekinumab reference arm was included (90 mg subcutaneous, every 8 weeks; n=63). At ECCO 2022 the 48-week results were presented, in which the placebo arm was not included.

Of the participants on guselkumab, 64.9% achieved clinical remission^a through week 48 (see Figure), as compared with 58.7% in participants treated with ustekinumab. In addition, corticosteroid-free clinical remission^b proportions ranged between 55.7% and 71.4% in the guselkumab arms and was 58.7% in the ustekinumab arm. Similarly, Patient Reported Outcome (PRO-2) remission^c at week 48 was achieved by 50.8%– 69.8% of the participants treated with guselkumab and 46.0% of the participants treated with ustekinumab.

Figure: Participants in clinical remission through week 48 [1]



 

 

 

 

 

The proportion of serious adverse events (AEs) was 7.3% for the combined guselkumab arms and 12.7% for the ustekinumab arm. No opportunistic infections, cases of tuberculosis, or deaths were reported in any study group.

Prof. Danese mentioned that the current study was not powered to directly compare the different guselkumab arms in terms of efficacy. He also emphasised that the ustekinumab arm was a reference arm only. He expects guselkumab to be superior to ustekinumab in patients with CD, since the mechanism of action of guselkumab is more specific. However, a direct comparison needs to be performed between the 2 agents to prove this.

a. Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) score <150.

b. Corticosteroid-free clinical remission is defined as a CDAI score <150 at week 48 and not receiving corticosteroids at week 48.

c. PRO-2 remission is defined as the unweighted CDAI component of daily abdominal pain score ≤1, and the unweighted CDAI component of daily average stool frequency score ≤3, and no worsening of abdominal pain or stool frequency from baseline.

1. Danese S, et al. Clinical efficacy and safety of guselkumab maintenance therapy in patients with moderately to severely active Crohn’s Disease: Week 48 analyses from the phase 2 GALAXI 1 study. OP24, ECCO 2022, 16–19 February.

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Posted on 12 April 20228 April 2024