Efficacy and Safety of Guselkumab for Crohn's Disease Through 3 Years: GALAXI-1 Long-Term Extension

Introduction: GALAXI-1 (NCT03466411) is a phase 2b study that evaluated guselkumab (GUS) in patients with moderate-to-severe Crohn’s disease (CD). We assessed clinical, endoscopic, and safety outcomes through 3 years in patients receiving GUS maintenance therapy in the GALAXI-1 long-term extension (LTE). Methods: Upon completing the treat-through Week (Wk)-48 study, patients continued in the LTE receiving maintenance regimens that were assigned at randomization: GUS 100 mg subcutaneous (SC) every 8 wks (q8w), GUS 200 mg SC q4w, or ustekinumab (UST) 90 mg SC q8w. Key efficacy endpoints assessed at Wk 144 included CD Activity Index (CDAI) clinical remission, patient-reported outcome (PRO)-2 remission, and endoscopic response. Efficacy analysis sets are defined in Table 1. Safety analyses included all treated patients. Results: Average duration of follow-up from baseline through Wk 152 was 100.9 wks in the combined GUS group (n=220) and 102.7 wks in the UST group (n=114); 151 patients randomized to GUS and 48 patients randomized to UST were treated in the LTE. Study drug discontinuations in the combined GUS group from Wks 48 to 152 were due to adverse events (AE, n[%]: 6[4.0]), lack of efficacy (2[1.3]), CD-related surgery (1[0.7]), lost to follow-up (4[2.6]), protocol deviation (1[0.7]), pregnancy (1[0.7]), refusal (1[0.7]), and patient withdrawal (9[6.0]). Among all randomized patients in the combined GUS group (including those who did not enter the LTE; primary efficacy analysis set), 54.1% were in CDAI clinical remission, 51.4% were in PRO-2 remission, and 34.7% were in endoscopic response at Wk 144 (Table 1). Outcomes among those who entered the LTE and among those with available data at each visit are summarized in Table 1. In the combined GUS group, serious AEs (SAEs, n[%]: 35[15.9]) and serious infections (12[5.5]) were infrequent. Most infections were not serious, mild to moderate in severity, and resolved without drug withdrawal. No cases of active tuberculosis, opportunistic infections, anaphylactic/serum sickness reactions, major adverse cardiovascular events, or deaths occurred during the LTE. Conclusion: Durable clinical and endoscopic efficacy were maintained over time through Wk 144 of the LTE. The safety profile of GUS was consistent with that of the approved indications. Most infections were not serious and did not result in discontinuation, while incidences of SAEs and serious infections were generally low. Table 1. - Clinical efficacy and endoscopic outcomes at Week 144 Outcome Analysis Population Combined Guselkumaba Ustekinumabb Clinical remission (CDAI< 150), % (n/N) Primary efficacy analysis set (NRI)c 54.1 (100/185) 46.0 (29/63) LTE efficacy analysis set (NRI)d 68.2 (103/151) 64.6 (31/48) Observed case analysis sete 95.4 (103/108) 83.8 (31/37) PRO-2 remission (AP mean daily score ≤1 and SF mean daily score ≤3, and no worsening of AP or SF from baseline), % (n/N) Primary efficacy analysis set (NRI)c 51.4 (95/185) 39.7 (25/63) LTE efficacy analysis set (NRI)d 64.2 (97/151) 58.3 (28/48) Observed case analysis sete 89.8 (97/108) 75.7 (28/37) Endoscopic response (≥50% improvement from baseline in SES-CD or SES-CD ≤2), % (n/N) Primary efficacy analysis set (NRI)c 34.7 (61/176) 19.4 (12/62) LTE efficacy analysis set (NRI)d 43.0 (61/142) 25.5 (12/47) Observed case analysis sete 73.5 (61/83) 41.4 (12/29) AP, abdominal pain; CDAI, Crohn's Disease Activity Index; LTE, long-term extension; NRI, nonresponder imputation; PRO-2, patient-reported outcome components of the CDAI [AP and SF]; SES-CD, Simple Endoscopic Score for Crohn’s Disease; SF, stool frequency.aIncludes patients randomized to the following guselkumab induction/maintenance regimens: 200 mg IV q4w→100 mg SC q8w; 600 mg IV q4w→200 mg SC q4w; 1200 mg IV q4w→200 mg SC q4w.bPatients randomized to ustekinumab.cPrimary efficacy analysis set consists of randomized patients who received ≥1 dose of study medication, with NRI for patients with treatment failure or missing data, including those who did not enter the LTE.dLTE efficacy analysis set consists of randomized patients who entered the LTE and received ≥1 dose of study medication in the LTE, with NRI for patients with treatment failure or missing data.eObserved case analysis set consists of randomized patients who entered the LTE, received ≥1 dose of study medication in the LTE, and had available data at the outcome visit. Patients who received dose adjustment were excluded.