S810 Efficacy Outcomes by Symptom-Based Response Status After Induction: Week-48 Results from the GALAXI 1 Trial of Guselkumab in Crohn’s Disease

Introduction: The GALAXI 1 study evaluated the efficacy and safety of guselkumab (GUS) in patients (pts) with moderate to severe Crohn’s disease (CD). The study employed a “treat-through" design in which all pts randomized to active treatment continued that treatment through week (Wk) 48, regardless of response to intravenous (IV) induction. Here, we report a post hoc analysis of clinical and endoscopic efficacy outcomes to GUS maintenance treatment in pts with symptom-based response to induction treatment. Methods: Pts were randomized 1:1:1:1:1 to induction with GUS 200, 600, or 1200mg IV, ustekinumab (UST) ∼6mg/kg IV, or PBO IV. At Wk12, pts transitioned to maintenance dosing as follows: GUS 200mg IVà100mg SC q8w, GUS 600mg IVà200mg SC q4w, GUS 1200mg IVà200mg SC q4w, UST ∼6mg/kg IVà90mg SC q8w, PBO CDAI clinical non-respondersàUST ∼6mg/kg IVà90mg SC q8w, and PBO CDAI clinical responders àPBO SC q4w. Response to induction was defined as ≥30% decrease from baseline to Wk12 in average daily stool frequency and/or abdominal pain score and both not worse than baseline. Analyses of Wk48 endpoints were prespecified but not controlled for multiplicity. The study was not powered to evaluate differences in efficacy among treatment groups at Wk48 and UST was used as a reference arm. Results: Of pts in the primary efficacy analysis set, 43/61 (70%), 46/63 (73%), and 41/61 (67%) in the respective GUS 200, 600, and 1200mg groups, 45/63 (71%) in the UST group, and 23/61 (38%) in the PBO group exhibited response to induction. Percentages of pts in response after induction who achieved clinical remission at Wk48 ranged from 63% to 89% among GUS dose groups compared with 57% to 73% in the overall population (Table). Most pts in clinical remission at Wk48 were also in corticosteroid-free remission. PRO-2 remission rates at Wk48 among pts in response after induction ranged from 59% to 80%, and CDAI clinical response rates ranged from 73% to 96%. Endoscopic response rates ranged from 49% to 56%. Conclusion: This post hoc analysis of a study with a “treat-through” design showed that pts randomized to GUS who were in symptom-based response after induction were more likely to achieve clinical and endoscopic outcomes at Wk48 compared with the overall population, regardless of the induction dose received. The “treat-through” study design allows for the evaluation of outcomes during maintenance in all pts randomized to treatment, rather than only induction responders. Table 1. - Efficacy Outcomes at Week 48 Overall and in Patients with Symptom-based Response to Induction Treatment Guselkumab 200 mg IVà100 mg SC 600 mg IVà 200 mg SC 1200 mg IVà200 mg SC Ustekinumab∼6 mg/kg IVà90 mg SC q8w Overall a Resp a Overall a Resp a Overall a Resp a Overall a Resp a N 61 43 63 46 61 41 63 45 CDAI clinical remission (CDAI score < 150) b, c 64% 72% 73% 89% 57% 63% 59% 69% Corticosteroid-free CDAI clinical remission (CDAI score < 150 at Wk 48 and not receiving corticosteroids at Wk 48) b, c 59% 67% 71% 87% 56% 61% 59% 69% PRO-2 remission (unweighted CDAI component of daily average AP score ≤1 AND the unweighted CDAI component of daily average SF ≤3, and no worsening of AP or SF from baseline) b, c 57% 63% 70% 80% 51% 59% 46% 51% CDAI clinical response (≥100-point reduction from baseline in CDAI score or CDAI score < 150) b, c 74% 81% 84% 96% 67% 73% 68% 78% Endoscopic response (≥50% improvement from baseline in SES-CD or SES-CD ≤2) b, c 44% 49% 46% 54% 44% 56% 30% 31% AP=Abdominal pain; CDAI=Crohn’s disease activity index; IV=Intravenous; PRO-2=Patient-reported CDAI components of abdominal pain and stool frequency; SC=subcutaneous; SES-CD=Simple Endoscopic Score for Crohn’s Disease; Wk=week.a“Overall” defined as all randomized patients who were in the primary efficacy analysis set of the treat-through study; “Resp” defined as ≥30% decrease from baseline at Wk12 in average daily SF and/or AP score and both not worse than baseline.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.

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