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Background

Endoscopic healing has become a critical treatment target in Crohn’s disease (CD). Risankizumab (RZB), a humanized immunoglobulin G1 monoclonal antibody against the p19 subunit of interleukin 23, is being investigated as a treatment for moderate-to-severe CD. This analysis assessed different endoscopic endpoints in patients treated with RZB induction therapy in twodouble-blind, randomised, placebo (PBO)-controlled studies (ADVANCE [NCT03104413] and MOTIVATE [NCT03105128]).

Methods

Patients with moderate-to-severe CD (CD Activity Index [CDAI] of 220–450, Simple Endoscopic Score for CD [SES‑CD] ≥ 6 [≥ 4 for isolated ileal disease] excluding the narrowing component, and average daily [liquid/very soft] stool frequency [SF] ≥ 4 and/or average daily abdominal pain [AP] score ≥ 2) who had demonstrated prior inadequate response or intolerance to conventional and/or biologic treatment (ADVANCE) or to biologic treatment (MOTIVATE) were randomised 2:2:1 (ADVANCE) or 1:1:1 (MOTIVATE) to receive intravenous (IV) RZB 600 mg, RZB 1200 mg, or PBO at weeks 0, 4, and 8. This analysis evaluated the proportion of patients who achieved endoscopic remission ulcer-free endoscopy (ie, absence of ulcers), and composite endpoints of CDAI clinical response and endoscopic response, and enhanced clinical response and endoscopic response at week 12 (endpoints defined in Figure 1 footnotes). All endoscopies were centrally read by a blinded reviewer. Safety was assessed throughout the studies.

Results

In ADVANCE and MOTIVATE, 850 and 569 patients, respectively, were randomised and included in the intent-to-treat population for this analysis. At week 12 greater proportions of RZB- vs PBO-treated patients in both studies achieved endoscopic remission (P ≤ .001), ulcer-free endoscopy (P ≤ .01), CDAI clinical response and endoscopic response (P ≤ .001), and enhanced clinical response and endoscopic response (P ≤ .001; Figure 1). Treatment with RZB 600 mg or 1200 mg was well tolerated, and no new safety risks were identified.1,2

1.  D’Haens G et al. ADVANCE study. Abstract presented at Digestive Disease Week 2021; 21-23 May 2021; Virtual.

2.  AbbVie In. (7 Jan 2021). Risankizumab (SKYRIZI®) Demonstrates Significant Improvements in Clinical Remission and Endoscopic Response in Two Phase 3 Induction Studies in Patients with Crohn's Disease [Press release]. Retrieved from https://news.abbvie.com/news/press-releases/risankizumab-skyrizi-demonstrates-significant-improvements-in-clinical-remission-and-endoscopic-response-in-two-phase-3-induction-studies-in-patients-with-crohns-disease.htm

Conclusion

Induction therapy with IV RZB 600 mg or 1200 mg resulted in improved outcomes at week 12 compared with PBO as assessed by endoscopy and by composite endoscopic-clinical endpoints in patients with moderate-to-severe CD.

Filgotinib (FIL) is a preferential Janus kinase 1 inhibitor in development for the treatment of inflammatory bowel disease. SELECTION was a phase 2b/3 randomized, double-blind, placebo (PBO)-controlled trial to evaluate FIL for the treatment of moderately to severely active ulcerative colitis (UC) (NCT02914522). The aim of this post hoc analysis was to assess the speed of improvement in patient-reported outcomes (PROs) during FIL treatment.

Eligible patients who were biologic-naïve or -experienced were enrolled in induction study A or induction study B, respectively. In each study, patients were randomized 2:2:1 to receive FIL 100 mg, FIL 200 mg or PBO once daily orally for 10 weeks. In this post hoc analysis, data from daily patient diaries up to day 15 of induction, including Mayo stool frequency subscores (SF; range, 0 [normal] to 3 [≥5 stools/day more than normal]) and rectal bleeding subscores (RB; range, 0 [no blood] to 3 [passing blood alone]), were used to evaluate the proportion of patients achieving predefined subscores or subscore reductions.

Induction studies A and B comprised 659 and 689 patients, respectively. Baseline characteristics were similar across treatment groups within induction study A and within induction study B. In induction study A, more patients treated with FIL 200 mg vs PBO reported a reduction in SF of ≥1 from baseline as early as day 6 (FIL 200 mg, 35.8%; PBO, 20.6%, p<0.01) and every day from day 10 (Figure 1), and a reduction in RB of ≥1 from baseline as early as day 4 (FIL 200 mg, 36.9%; PBO, 23.7%; p<0.01) and every day from day 7 (Figure 2). In induction study B, more patients treated with FIL 200 mg vs PBO reported a reduction in SF of ≥1 from baseline as early as day 2 (FIL 200 mg, 21.6%; PBO, 12.1%; p<0.05) (Figure 3) and a reduction in RB of ≥1 from baseline as early as day 3 (FIL 200 mg, 29.5%; PBO, 17.6%; p<0.01) (Figure 4). More patients receiving FIL 200 mg vs PBO achieved the composite score of RB=0 and SF≤1 as early as day 9 in induction study A (FIL 200 mg, 18.8%; PBO, 9.5%, p<0.05). More patients receiving FIL 200 mg vs PBO achieved the composite score of RB=0 and SF≤1 as early as day 7 in induction study B (FIL 200 mg, 10.7%; PBO, 4.2%, p<0.05).

In this post hoc analysis of induction study data from SELECTION, improvements in SF and RB were observed within the first week of therapy with FIL 200 mg, compared with PBO, in patients with moderately to severely active UC. These data demonstrate that FIL 200 mg has rapid onset of action, as assessed by PROs, in both biologic-naïve and biologic-experienced patients.