Patients with moderately to severely active Crohn’s disease who experienced inadequate response to guselkumab maintenance therapy may benefit from dose escalation to 200 mg every 4 weeks, according to long-term extension data from the Phase 3 GALAXI 2 and 3 studies. Investigators reported sustained clinical and endoscopic improvements through Week 96, with safety outcomes remaining consistent with the established profile of the IL-23p19 inhibitor.

Study Findings From the GALAXI 2 and 3 Trials

The GALAXI 2 and 3 Phase 3 studies evaluated guselkumab, a dual-acting IL-23p19 subunit inhibitor, in patients with moderately to severely active Crohn’s disease. During the maintenance phase, participants received either guselkumab 100 mg subcutaneously every 8 weeks or 200 mg every 4 weeks.

In the long-term extension phase, patients with inadequate response between Weeks 52 and 80 were eligible for a one-time dose adjustment to guselkumab 200 mg every 4 weeks. Inadequate response was defined as failure to achieve clinical response, measured by at least a 100-point reduction in Crohn’s Disease Activity Index (CDAI) score from baseline or CDAI below 150, combined with CDAI of at least 220.

A total of 64 patients underwent dose adjustment or sham adjustment, including 36 patients who escalated from 100 mg every 8 weeks to 200 mg every 4 weeks. Among evaluable patients who switched dosing regimens, 41.4% achieved clinical response and 31.0% achieved clinical remission within 16 weeks of dose escalation.

By Week 96, outcomes further improved. Investigators reported that 58.6% of patients achieved clinical response, while 48.3% reached clinical remission. Endoscopic outcomes were similarly encouraging, with 48.3% achieving endoscopic response and 34.5% achieving endoscopic remission.

Patients already receiving 200 mg every 4 weeks who underwent sham dose adjustment demonstrated efficacy outcomes generally similar to those observed in dose-escalated patients. Adverse event rates before and after dose adjustment were comparable, suggesting no new safety concerns emerged during prolonged therapy.

Clinical Implications for Crohn’s Disease Management

The findings provide additional evidence supporting individualized maintenance strategies in Crohn’s disease, particularly for patients who lose response during biologic therapy. Dose optimization has become an increasingly important approach in inflammatory bowel disease management as clinicians attempt to maintain remission and avoid corticosteroid exposure or surgery.

The sustained remission and endoscopic improvement observed after escalation to guselkumab 200 mg every 4 weeks may offer clinicians another therapeutic option before switching to an alternative biologic class. Endoscopic remission is especially relevant because mucosal healing is associated with improved long-term outcomes, including reduced hospitalization and surgical risk.

Safety findings were consistent with prior guselkumab studies and approved indications, reinforcing confidence in long-term IL-23 inhibition. However, investigators cautioned that interpretation is limited by the relatively small sample size in the dose-adjustment subgroup.

The results may help inform real-world treatment algorithms as gastroenterologists increasingly adopt precision-based biologic optimization strategies for refractory Crohn’s disease.

Panaccione R, Hisamatsu T, Afzali A, et al. Efficacy and safety of guselkumab in participants with moderately to severely active Crohn’s disease who had maintenance dose adjustment: results from the phase 3 GALAXI 2 & 3 long-term extension. Presented at: Digestive Disease Week, May 2-5, 2026. Chicago, Illinois.