GALAXI: Long-term outcomes of guselkumab in Crohn’s disease following maintenance dose adjustment

touchIMMUNOLOGY coverage of DDW 2026

Where does guselkumab fit in the treatment paradigm for CD?

Guselkumab, a selective IL-23 inhibitor, is increasingly being used as a first-line treatment for moderate-to-severe Crohn’s disease in many parts of the world. This is a result of its strong efficacy across both symptomatic and objective endpoints, together with the favourable safety profile of this therapeutic class. As a result, guselkumab is becoming an important first-line option where available. That said, many patients have already been treated with other advanced therapies or may need to receive a biosimilar anti-TNF. Reassuringly, guselkumab has also been shown to be effective in these populations.

Could you provide a brief overview of the 48-week GALAXI studies? 

GALAXI 2 and 3 were identical phase 3 studies that evaluated guselkumab in patients with moderately to severely active Crohn’s disease who had failed or were intolerant to conventional therapies or biologic therapies, except for ustekinumab. They were global, randomized, double-blind, treat-through trials, and they compared guselkumab to placebo and also to a ustekinumab active comparator arm. Patients enrolled in the studies received either of the induction therapies followed by subcutaneous dosing.

Across the studies, guselkumab demonstrated significant improvements in clinical remission, endoscopic response, endoscopic remission, and the composite of deep remission, which is a clinical and endoscopic endpoint compared with placebo through Week 48. The pooled analysis of the two trials showed superiority of guselkumab over ustekinumab, which has been one of our cornerstones of therapy for endoscopic outcomes. GALAXI 2 and 3 were the first double-blind phase 3 trials to demonstrate superiority to ustekinumab on those pre-specified endoscopic endpoints. Furthermore, the efficacy was shown to be durable in both the biologic-naive and the biologic-experienced patients.

Could you describe the aims and design of the long-term extension study?

The long-term extension phase of the GALAXI 2 and 3 studies was designed to evaluate the long-term efficacy, safety, and durability of response. The long-term extension study aimed to assess the maintenance of clinical remission, steroid-free remission, symptomatic improvement and quality-of-life benefits, while evaluating sustained endoscopic response and deep remission over time. It’s an ongoing study which is slated to last approximately 5 years.

At the same time, extension studies are important to characterize the long-term safety and tolerability of drugs like guselkumab, and look at factors including serious adverse events (SAEs), infections, malignancies, and immunogenicity.

What was particularly unique about the data presented at DDW in Chicago was the further evaluation of maintenance dosing strategies, including dose adjustments or escalation in patients who had an inadequate response to the doses they received during the main maintenance period or early in the long-term extension.

Within the main trial period, there were two dosing groups: 100 mg every 8 weeks and 200 mg every 4 weeks. Participants who were receiving the guselkumab 100 mg every 8 weeks who met predefined inadequate response criteria entering into the long-term extensions between weeks 52 and 80 underwent a dose escalation to the guselkumab 200 mg every 4 weeks. However, the patients who had already been on 200 mg every 4 weeks, underwent a blinded sham adjustment.

How well were the clinical endpoints met in patients who received dose adjustment?

The study assessed clinical response, clinical remission, endoscopic response 16 weeks after dose adjustment, and then the clinical and endoscopic endpoints were also assessed at Week 96. Following the dose adjustment from 100 mg every 8 weeks to 200 mg every 4 weeks, we saw clinical response and remission rates improve over time, with approximately half of the patients achieving clinical remission or the endoscopic response endpoint by Week 96. Interestingly, similar efficacy trends were observed in the patients already on the 200 mg every 4 weeks who underwent the sham adjustment and that is something that we need to understand better.

What was the safety profile of guselkumab in these patients at Week 96?

The safety profile following the dose adjustment remained consistent with the established safety experience of guselkumab, and there were no new safety signals or deaths observed over the follow-up to Week 96.