Efficacy of Guselkumab in Patients With Moderately to Severely Active Crohn's Disease Not in Clinical Response at Week 12: Results From the GALAXI 1 Study

Introduction: The Phase 2 GALAXI 1 study evaluated the efficacy and safety of guselkumab (GUS), a human selective IL-23p19 subunit antagonist, in patients (pts) with moderate to severe Crohn’s disease (CD). Pts were randomized to GUS, ustekinumab (UST), or placebo (PBO) through Week (Wk) 48 without rerandomization after IV induction. Previously, we reported that pts who were in clinical response after IV induction had higher rates of clinical and endoscopic outcomes at Wk48 than the overall study population.1 In this post hoc analysis, we report outcomes for pts who did not achieve Wk12 clinical response based on CD activity index (CDAI) after IV induction. Methods: Pts were randomized 1:1:1:1:1 to induction with GUS 200, 600, or 1200mg IV, UST ∼6mg/kg IV, or PBO IV. At Wk12 (Wk8 for UST), pts were transitioned to maintenance dosing: GUS 200mg IV→100mg subcutaneous (SC) q8w, GUS 600mg IV→200mg SC q4w, GUS 1200mg IV→200mg SC q4w, UST ∼6mg/kg IV→90mg SC q8w, PBO nonresponders→UST ∼6mg/kg IV→90mg SC q8w, and PBO responders→PBO SC q4w. Clinical response (all time points) was defined as ≥100-point reduction from baseline in CDAI or CDAI < 150. Other endpoints included clinical remission (CDAI < 150), pt-reported outcome (PRO)-2 remission (unweighted CDAI components of average daily abdominal pain score ≤1 and average daily stool frequency ≤3, and no worsening from baseline), and endoscopic response (≥50% improvement from baseline in simple endoscopic score [SES]-CD or SES-CD ≤2). The study was not powered to evaluate between-group efficacy differences at Wk48; UST was used for reference. Results: At Wk12, 63/185 (34.1%) GUS pts and 21/63 (33.3%) UST did not achieve CDAI clinical response. Among GUS Wk12 nonresponders, 46.0% were in clinical response by Wk24 (Table 1). Percentages of Wk12 nonresponders who went on to achieve outcomes at Wk48 in the GUS and UST groups, respectively, were as follows: clinical response, 58.7% and 47.6%; clinical remission, 41.3% and 33.3%; PRO-2 remission, 42.9% and 23.8%; and endoscopic response, 31.7% and 23.8% (Table 1). Conclusion: Among pts who were not in clinical response at Wk12, continued treatment with GUS SC may result in clinical response and, ultimately, clinical or PRO-2 remission and/or endoscopic response. 1. Panés J, et al. UEG Journal 2022; 10 (Suppl 8). Table 1. - Efficacy Outcomes Among Patients Not in Clinical Response(a) at Week 12 Outcome, %b c Combined Guselkumab (N=63) Ustekinumab (N=21) Clinical responsea Week 16 36.5 42.9 Week 20 47.6 52.4 Week 24 46.0 52.4 Week 28 47.6 42.9 Week 32 54.0 47.6 Week 36 50.8 57.1 Week 40 54.0 52.4 Week 44 52.4 47.6 Week 48 58.7 47.6 Clinical remission at Week 48d 41.3 33.3 PRO-2 remission at Week 48e 42.9 23.8 Endoscopic response at Week 48f 31.7 23.8 AP=abdominal pain; CD=Crohn’s disease; CDAI=Crohn’s disease activity index; PRO-2=Patient-reported CDAI components of AP and SF; SES-CD=Simple Endoscopic Score for CD; SF=stool frequency.aClinical response was defined as ≥100-point reduction from baseline in CDAI or CDAI < 150.bPatients who had a prohibited change in concomitant CD medication, a CD-related surgery, or discontinued study agent due to lack of efficacy, or an adverse event of worsening CD prior to the designated analysis timepoint, were considered not to have achieved the endpoint.cPatients who had insufficient data to calculate the outcome measure at the designated analysis timepoint were considered not to have achieved the endpoint.dClinical remission was defined as a CDAI < 150.ePRO-2 remission was defined as unweighted CDAI component of average daily AP ≤1 and the unweighted CDAI component of average daily SF ≤3, and no worsening of AP or SF from baseline.fEndoscopic response was defined as ≥50% improvement from baseline in SES-CD or SES-CD ≤2.