OP25 Patients with moderate to severe Crohn’s Disease with and without prior biologic failure demonstrate improved endoscopic outcomes with risankizumab: Results from phase 3 induction and maintenance trials

Abstract

Background Risankizumab (RZB), a selective interleukin-23 inhibitor, demonstrated clinically meaningful improvements in endoscopic outcomes in patients with moderate to severe Crohn’s disease (CD) during two phase 3 induction trials (ADVANCE and MOTIVATE) and the maintenance study (FORTIFY). Here, we compared the efficacy of RZB in inducing and maintaining improvements in endoscopic outcomes in patients with CD who demonstrated intolerance and/or inadequate response (IR) to biologic therapies (with prior bio-failure) versus those who demonstrated IR to conventional therapies only (without prior bio-failure). Methods Data included in this subgroup analysis included pooled data from patients randomized to receive intravenous (IV) RZB 600mg (N=527) or placebo (PBO) IV (N=362) every 4 weeks (wks) for 12wks during induction (ADVANCE+MOTIVATE), and data from patients receiving subcutaneous (SC) RZB 360mg (N=141) or withdrawn from RZB IV to receive PBO SC (withdrawal [PBO SC], N=164) every 8wks for 52-wks during maintenance. At Wks 12 and 52, endoscopic response, endoscopic remission, ulcer-free endoscopy (absence of ulceration), and deep remission (Wk52 only) were evaluated both in the overall population and in subpopulations of patients with and without prior bio-failure. (Endpoints are defined in Table footnotes). Safety was assessed throughout the studies. Results Approximately three-quarters of randomized patients included in this subgroup analysis had prior bio-failure (ADVANCE+MOTIVATE: 75.4%; FORTIFY: 73.8%). Higher rates of endoscopic response, endoscopic remission, and ulcer-free endoscopy were observed at Wk12 among patients receiving induction with RZB IV versus PBO IV. Subgroup analysis demonstrated treatment effects with risankizumab in patient subpopulations with and without prior bio-failure, with greater adjusted differences versus PBO in patients without prior bio-failure (Figure). At Wk52, endoscopic response, endoscopic remission, ulcer-free endoscopy, and deep remission rates favored RZB SC compared to withdrawal (PBO SC). Again, treatment effects were observed in patients with and without prior bio-failure, with greater adjusted differences versus withdrawal (PBO SC) in patients without prior bio-failure. RZB maintenance treatment was well-tolerated and no new safety signals were observed. The safety profile of RZB has been reported previously.1,2 Conclusion Induction and maintenance therapy with risankizumab achieved higher rates for endoscopic endpoints in patients with moderate to severe Crohn’s disease versus placebo, regardless of prior bio-failure status. However, numerically higher efficacy rates were observed in patients without prior bio-failure. 1 D’Haens, G. et al. in DDW 2021 2 Ferrante, M. et al. in UEGW 2021

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“…Risankizumab was also able to achieve higher rate of patients with clinical response, endoscopic remission, 21 corticosteroids ,CS‐free remission, 22 higher improvement of biomarkers (hs‐CRP and fecal calprotectin), 23 and reductions in hospitalizations and surgeries at week 52 compared to withdrawal/PBO 21,24 . Patients without prior bio‐failure (53.8% of patients with endoscopic response at week 52 compared to 43.7% of patients with a biologic experience), with any colonic involvement ( p < 0.001) and with short CD duration seemed to be the best responders 25–28 . Only one real‐world study from a Belgian multicentric cohort of multi‐refractory CD patients (95% had been exposed to more than 3 biologicals) has been published to date 29 .…”

“…5-ASA, 5aminosalicylic acid; CSF-1R, Colony Stimulating Factor-1 Receptor; DNA, deoxyribonucleic acid; FKN, fractalkine; HDAC, Histone deacetylase inhibitor; IFX, infliximab; IL, interleukin; Inhib., inhibitor; LANCL2, Lanthionine synthetase C-like 2; MAP, mycobacterium avium subspecies paratuberculosis; NLRX1, nucleotide-binding oligomerization domain, leucine rich repeat containing X1; R, receptor; SGLT2, sodium/glucose cotransporter 2; S1P, sphingosine-1-phosphate; SGLT2, sodium/glucose cotransporter 2; SIK, salt-inducible kinase; TLR, toll like receptor; UST, ustekinumab duration seemed to be the best responders. [25][26][27][28] Only one real-world study from a Belgian multicentric cohort of multi-refractory CD patients (95% had been exposed to more than 3 biologicals) has been published to date. 29 One third of these CD patients obtained a clinical remission and endoscopic response at week 24 with risankizumab and none of the patients experienced serious infections or intolerance.…”

“… 21 , 24 Patients without prior bio‐failure (53.8% of patients with endoscopic response at week 52 compared to 43.7% of patients with a biologic experience), with any colonic involvement ( p < 0.001) and with short CD duration seemed to be the best responders. 25 , 26 , 27 , 28 Only one real‐world study from a Belgian multicentric cohort of multi‐refractory CD patients (95% had been exposed to more than 3 biologicals) has been published to date. 29 One third of these CD patients obtained a clinical remission and endoscopic response at week 24 with risankizumab and none of the patients experienced serious infections or intolerance.…”