Dados do Trabalho

Título

RISANKIZUMAB INDUCTION THERAPY IN PATIENTS WITH MODERATE-TO-SEVERE CROHN’S DISEASE: RESULTS FROM THE ADVANCE AND MOTIVATE PHASE 3 STUDIES

Introdução

Risankizumab (RZB) is a monoclonal antibody against interleukin-23, a key cytokine in the pathogenesis of Crohn’s disease (CD). Here we report results of ADVANCE (NCT03105128) and MOTIVATE (NCT03104413), two similar double-blind randomized placebo-controlled ph 3 studies evaluating efficacy and safety of RZB as induction therapy in patients (pts) with moderate to severe CD.

Objetivo

To evaluate efficacy and safety of RZB as induction in mod-to-severe CD.

Método

Eligible pts had a CDAI 220-450, average (avg) daily (liquid/very soft) stool frequency (SF) ≥4 and/or avg daily abdominal pain score (APS) ≥2, and SES-CD ≥6 (≥4 for isolated ileal disease) excluding the narrowing component, and demonstrated inadequate response (IR) or intolerance to biologic (bio-IR) and/or conventional treatment (non-bio-IR) (ADVANCE), or bio-IR only (MOTIVATE). Pts were randomized 2:2:1 (ADVANCE) or 1:1:1 (MOTIVATE) to receive IV RZB 600 mg, 1200 mg, or placebo (PBO) at Weeks 0, 4, and 8. Randomization was stratified by baseline (BL) corticosteroid use, BL SES-CD, and number of prior biologics failed. Co-primary endpoints (eps) were clinical remission and endoscopic response (defined in tables footnotes) at Week 12. Safety was assessed in pts receiving ≥1 dose of study drug.

Resultados

The primary ITT populations included 850 pts in ADVANCE and 569 in MOTIVATE. In both studies, significantly more pts in RZB 600 mg and 1200 mg groups vs PBO (P<0.001) achieved the co-primary eps (Tables 1 and 2). In ADVANCE, RZB showed efficacy regardless of biologic IR status by subgroup analysis; non-bio-IR pts had numerically higher rates of efficacy vs bio-IR pts (Table 1). Adverse event (AE) rates were similar in the RZB 600 mg and 1200 mg groups vs PBO. Serious AEs, AEs leading to discontinuation of study drug, and serious infections were numerically higher in the PBO group, due at least in part to AEs related to uncontrolled activity of CD (Table 3). No adjudicated MACE or adjudicated anaphylaxis were reported. Active TB was reported in 1 patient (pt) with history of active TB in the ADVANCE RZB 600 mg group. Two deaths were reported in the ADVANCE PBO group and 1 in the MOTIVATE RZB 1200 mg group (pt had squamous cell lung carcinoma).

Conclusão

RZB 600 mg and 1200 mg was more effective than placebo at inducing clinical remission and endoscopic response at Week 12 in pts with moderate-to-severe CD. Both RZB doses were generally well-tolerated, and AEs were consistent with the known safety profile of RZB.

Palavras-Chave

risankizumab, Crohn’s disease, efficacy, safety