Data from the ongoing open-label long-term extension (OLE) of the phase III FORTIFY trial presented at AIBD 2024 support the role of risankizumab for the treatment of moderate-to-severe active Crohn’s disease (CD).

The OLE comprised participants who completed 52 weeks of risankizumab maintenance in the FORTIFY substudies or phase II OLE. Risankizumab was given subcutaneously at a dose of 180 mg Q8W. Those who had prior rescue therapy or received rescue therapy during OLE continued SC risankizumab 360 mg.

Sustained QoL improvements

At the end of the randomized double-blind withdrawal maintenance phase (week 52), most of the participants achieved the meaningful within-person change (MWPC) thresholds for IBDQ* response (≥16-point increase in total score; 75.5 percent), IBDQ remission (total score ≥170 points; 65 percent), SF-36 PCS (≥4.1 points; 67.7 percent) and MCS** (≥3.9 points; 60.7 percent) improvements, and FACIT-Fatigue*** response (≥9-point increase; 80.5 percent).

These improvements were sustained through week 104 (n=257), wherein most patients sustained MWPC thresholds for IBDQ response (70.8 percent), IBDQ remission (59.5 percent), SF-36 PCS (64.6 percent) and MCS (57.2 percent) improvements, and FACIT-Fatigue response (78.2 percent). [AIBD 2024, abstract S5]

The debilitating and progressive nature of CD impairs the health-related quality of life (HRQoL) of CD patients. “[These data show that] CD patients who completed risankizumab treatment in the FORTIFY maintenance study and had an additional 52 weeks of treatment in the OLE demonstrated sustained HRQoL improvements that were clinically meaningful,” said the researchers.

Endoscopic improvements

Another analysis explored the association between endoscopic healing and long-term outcomes in CD patients on risankizumab maintenance. Participants from the FORTIFY maintenance phase who achieved clinical outcomes at week 104 were evaluated based on the achievement of endoscopic response at week 52. [AIBD 2024, abstract S7]

Participants from the ADVANCE and MOTIVATE induction trials who achieved clinical response to IV risankizumab at week 12 were also eligible to enrol in the FORTIFY maintenance phase. They were rerandomized to SC risankizumab 180/360 mg or placebo Q8W for 52 weeks. Patients who completed the maintenance study could receive open-label risankizumab as per their treatment assignment.

At week 52, more than half of the 257 patients included in this analysis achieved endoscopic response (>50-percent reduction in SES-CD^# from induction baseline [BL]). Moreover, about 40 percent achieved endoscopic remission (SES-CD ≤4, ≥2-point reduction from BL, no subscore >1 in any individual variable), while 30.7 percent had ulcer-free endoscopy (SES-CD ulcerated surface subscore 0 in patients with subscore ≥1 at induction BL).

More patients who achieved endoscopic response at week 52 also achieved CD activity index (CDAI) response (≥100-point reduction from induction BL), CDAI remission (CDAI <150), SF/AP^## remission (average daily ≤2.8/≤1), SF remission, AP remission, and steroid-free SF/AP remission (not on corticosteroids at corresponding visit; in clinical remission; p≤0.01 for all) at week 104.

Similarly, more patients who achieved endoscopic remission at week 52 achieved CDAI response and AP remission (p≤0.05 for both), as well as CDAI, SF/AP, SF, and steroid-free SF/AP remission (p≤0.01 for all) at week 104.

Week 104 also saw more patients achieving CDAI, SF/AP, and SF remission (p≤0.05 for all), as well as steroid-free SF/AP remission (p≤0.01), among those who had ulcer-free endoscopy at week 52.

“Endoscopic healing is an important long-term treatment goal in CD per STRIDE II^### consensus recommendations … [In this analysis,] a significantly higher proportion of patients achieved long-term improvement in clinical outcomes when they achieved endoscopic outcomes at the end of risankizumab maintenance treatment,” the researchers said.

*IBDQ: Inflammatory Bowel Disease Questionnaire

**SF-36 PCS/MCS: 36-Item Short Form Survey physical component score/mental component score

***FACIT-Fatigue: Functional Assessment of Chronic Illness Therapy ? Fatigue

^#SES-CD: Simple Endoscopic Score for CD

^##SF/AP: Stool frequency/Abdominal pain

^###STRIDE II: An update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease