The Association of Endoscopic Outcomes With Improvement in Long-Term Clinical Outcomes in Patients With Moderate to Severe Crohn’s Disease Treated With Risankizumab: Results from the Phase 3 FORTIFY Open-Label Extension Trial

Background:
Endoscopic healing is an important long-term treatment goal in Crohn’s disease (CD) per STRIDE II consensus recommendations. Here, the relationship between endoscopic healing and long-term outcomes were assessed in patients with CD who received risankizumab (RZB) maintenance treatment.
Methods:
In this analysis, patients who achieved clinical outcomes at week 104 of the FORTIFY maintenance study (NCT03105102), which included CD activity index (CDAI) remission (CDAI < 150), CDAI response (reduction of CDAI ≥100 points from induction baseline [BL]), stool frequency (SF)/abdominal pain score (APS) remission (average [avg] daily SF ≤2.8 and avg daily APS ≤1, neither worse than BL of induction), SF remission (avg daily SF ≤2.8 and not worse than induction BL), AP remission (avg daily APS ≤1, and not worse than induction BL), and steroid-free SF/APS remission (ie, not receiving corticosteroids at the corresponding visit and in clinical remission) were compared based upon achievement of week 52 endoscopic response (decrease in the Simple Endoscopic Score for CD [SES-CD] >50% from induction BL [or for patients with isolated ileal disease and a BL SES-CD=4, ≥2 point reduction from induction BL]) vs not, endoscopic remission (SES-CD ≤4, ≥2 point reduction from BL, and no subscore >1 in any individual variable) vs not, or ulcer-free endoscopy (SES-CD ulcerated surface subscore of 0 in patients with SES-CD ulcerated surface subscore ≥1 at induction BL) vs not. Briefly, in the ADVANCE and MOTIVATE induction trials, patients who achieved clinical response to intravenous RZB at week 12 were eligible to enter the FORTIFY maintenance trial; patients were rerandomized to receive subcutaneous RZB 180/360 mg or placebo (PBO) every 8 weeks for 52 weeks. An endoscopy was performed at week 52. Patients who completed the maintenance study could receive open-label RZB as per their treatment assignment. SF score and APS, as well as the composite CDAI score, were collected every 24 weeks. Patients with missing clinical outcomes at week 104 were imputed as nonresponders. The proportions of patients who achieved clinical outcomes at week 104 were evaluated using chi-square tests. Patients who received PBO during maintenance were excluded from this analysis. Endoscopies were scored by a central reviewer.
Results:
Of the 257 patients included in the analyses, 134 (52.1%), 99 (38.5%), and 79 (30.7%) patients achieved endoscopic response, endoscopic remission, and ulcer-free endoscopy, respectively, at week 52. Significantly more patients who achieved week 52 endoscopic response also achieved CDAI remission, CDAI response, SF/AP remission, SF remission, AP remission, and steroid-free SF/APS remission at week 104 (P≤.01 for all comparisons). Likewise, significantly more patients who achieved week 52 endoscopic remission achieved CDAI remission, SF/AP remission, SF remission, and steroid-free SF/APS remission at week 104 (P≤.01) and attained CDAI response and AP remission at week 104 (P≤.05). Lastly, among patients who achieved week 52 ulcer-free endoscopy, significantly more patients achieved CDAI remission (P≤.05), SF/APS remission (P≤.05), SF remission (P≤.05), and steroid-free SF/APS remission (P≤.01) at week 104.
Conclusions:
A significantly higher proportion of patients achieved long-term improvement in clinical outcomes when they achieved endoscopic outcomes at the end of RZB maintenance treatment.