P0917 Corticosteroid sparing effects of treatment with guselkumab in patients with moderate to severely active Crohn’s disease: Phase 3 GALAXI 2/3 results through week 48

Background

GALAXI 2 & GALAXI 3 (G2 & G3) are identical 48-week (Wk), randomized, double-blind, head-to-head, placebo- and active-comparator (ustekinumab; UST) treat-through trials assessing the efficacy and safety of guselkumab (GUS), a dual-acting IL-23p19 subunit inhibitor, in participants (pts) with Crohn’s disease (CD). Here we report the corticosteroid (CS)-sparing effects of treatment with GUS vs UST from the pooled G2 & G3 studies through Wk48.

Methods

Pts with moderately to severely active CD (based on CDAI and SES-CD scoring) and inadequate response or intolerance to conventional or biologic (BIO-IR) therapy were eligible. Pts were randomized 2:2:2:1 to GUS 200mg IV q4w(x3)→200mg SC q4w, GUS 200mg IV q4w(x3)→100mg SC q8w, UST ~6mg/kg IV(x1)→90mg SC q8w, or placebo. Pts receiving oral CS upon entry (up to 40mg/day of prednisone-equivalent dose) were required to begin tapering their daily CS dose at Wk12, unless not medically feasible. CS use and 90-day CS-free clinical outcomes at Wk48 were assessed vs UST.

Results

The primary analysis (all pts) included 508 (G2) and 513 (G3) pts. Baseline (BL) characteristics were similar across trials: mean [SD] CDAI (G2: 295.0 [52.0], G3: 294.7 [53.8]), mean [SD] SES-CD (13.1 [7.3], 12.8 [7.3]), BIO-IR history (52.8%, 51.9%), BIO-naïve (41.9%, 41.5%), and oral CS use (37.4%, 36.1%). In analyses of pooled data (G2+G3), the proportion of pts receiving oral CS at BL was similar across treatment groups (GUS 100mg q8w: 38.1%; GUS 200mg q4w: 35.8%; UST: 37.5%). Greater proportions of pts receiving both GUS doses achieved 90-day CS-free Wk-48 outcomes of endoscopic response vs UST (100 mg q8w vs UST: ∆11.2%; 200 mg q4w vs UST: ∆14.5%), endoscopic remission (∆9.5%, ∆11.9%), the composite endpoint of clinical remission + endoscopic response (∆8.1%, ∆12.4%), the composite endpoint of clinical remission + endoscopic remission (∆8.0%, ∆10.9%), and clinical remission (∆4.1%, ∆5.3%) (Table 1). The 90-day CS-free outcomes vs UST in BIO-IR and BIO-naïve pts in the primary analysis were also assessed at Wk48 (Table 1).

Among all pts receiving oral CS at BL, greater proportions of GUS-treated pts (100mg q8w: 71.6%; 200mg q4w: 75.5%) were not receiving CS at Wk 48 vs UST (67.0%). Also, among all pts receiving oral CS at BL, greater proportions of GUS-treated pts achieved 90-day CS-free outcomes at Wk48 vs UST, including endoscopic response (41.3%, 42.5% vs 31.2%) and endoscopic remission (30.3%, 28.3% vs 20.2%), and similar proportions for clinical remission (52.3%, 54.7% vs 53.2%).

Conclusion

In CD, greater proportions of GUS-treated pts achieved CS-free endoscopic-based efficacy outcomes through Wk48 vs UST, regardless of prior biologic exposure status.