P516 Serological biomarkers of tissue remodeling are associated with endoscopic remission in Crohn’s disease patients treated with GED-0301 (mongersen)

Abstract Background In Crohn’s disease (CD) Smad7 is overexpressed in the intestinal mucosa, where it contributes to a sustained production of inflammatory cytokines, increased matrix metalloproteinase (MMP) activity and chronic inflammation through inhibition anti-inflammatory actions TGF-beta. GED-0301, an anti-sense oligodeoxynucleaotide complementary mRNA Smad7, inhibits translation synthesis protein. We investigated exploratory biomarkers collagen degradation by MMPs (C1M, C3M, C4M) formation (PRO-C3, PRO-C4 PRO-C5) their association with endoscopic remission CD patients treated GED-0301. Methods 63 were randomized (1:1:1) 4, 8 or 12 weeks oral, blinded GED-0301 160 mg daily (ClinicalTrials.gov no: NCT02367183). Simple score for (SES-CD) (centrally read) was used evaluate activity. Remission defined as SES-CD≤4 at week 12. 54 completed 12-week induction phase. Serum measured competitive ELISA se included C1M, C4M, PRO-C3, PRO-C4, PRO-C5 baseline, Spearman rho correlation applied SES-CD score. Results Seven (11%) achieved At baseline biomarkers, C1M (baseline: r=0.36, P=0.005; wk12: r=0.47, P=0.0007), C3M r=0.46, P=0.0002; r=0.28, P=0.047), C4M r=0.40, P=0.002; P=0.011) P=0.004; r=0.35, P=0.013), r=0.30, P=0.022) correlated (table 1). Remitters showed numerically lower serum levels (54ng/mL vs. 65ng/mL), (14.7ng/mL 16.5ng/mL), (241ng/mL 299ng/mL) (442ng/mL 660ng/mL) compared non-remitters. The (P<0.05), (P<0.05) significantly suppressed remitters non-remitters (figure same also demonstrated suppression concentrations (C1M: 21.6% decrease from 12; C4M: 15% PRO-C5: 26.6% 12) Conclusion Biomarkers tissue remodeling scores mongersen. Patients s who based on criteria showing greater these relative Collectively, data suggest that may be useful monitoring mucosal changes patients.