RPC4046, a Monoclonal Antibody Against IL13, Reduces Histologic and Endoscopic Activity in Patients With Eosinophilic Esophagitis GASTROENTEROLOGY Hirano, I., Collins, M. H., Assouline-Dayan, Y., Evans, L., Gupta, S., Schoepfer, A. M., Straumann, A., Safroneeva, E., Grimm, M., Smith, H., Tompkins, C., Woo, A., Peach, R., Frohna, P., Gujrathi, S., Penenberg, D. N., Li, C., Opiteck, G. J., Olson, A., Aranda, R., Rothenberg, M. E., Dellon, E. S., Donnellan, F., Iacucci, M., Paterson, W., Schoepfer, A., Abonia, P., Ayub, K., Coates, A., Cohen, S., Dellon, E., Desta, T., Falk, G., Fein, S., Fernandez-Becker, N., Fleischer, D., Friedenberg, K., Ghishan, F., Glover, S., Goldstein, G., Gopal, V., Gross, C., Nardi, R., Kugathasan, S., Lacy, B., Lewis, J., Menard-Katcher, P., Mitlyng, B., Moawad, F., Perez, R., Peterson, K., Ramirez, F., Reeves-Darby, V., Schey, R., Shad, J., Vaezi, M., Wo, J., Zakko, S., HEROES Study Grp 2019; 156 (3): 592-+


Eosinophilic esophagitis (EoE) is a chronic, esophageal, type 2 inflammatory response associated with increased serum levels of interleukin 13 (IL13), which might contribute to its pathogenesis. RPC4046, a recombinant humanized monoclonal antibody against IL13, prevents its binding to the receptor subunits IL13RA1 and IL13RA2. We performed a phase 2 trial to evaluate the efficacy and safety of RPC4046 in patients with EoE.We performed a multicenter, double-blind trial of 99 adults with active EoE randomly assigned (1:1:1) to groups given RPC4046 (180 or 360 mg) or placebo once weekly for 16 weeks, from September 2014 through December 2015. Patients were seen at day 1 (baseline) and weeks 2, 4, 8, 12, and 16. They underwent esophagogastroduodenoscopy and biopsies were collected at baseline and week 16. Patients completed a daily dysphagia symptom diary through week 16 and patient-reported outcome data were collected. The primary outcome was change in mean esophageal eosinophil count in the 5 high-power fields (hpfs) with the highest level of inflammation.At week 16, mean changes in esophageal eosinophil count per hpf were a reduction of 94.8 ± 67.3 in patients who received 180 mg RPC4046 (P < .0001) and a reduction of 99.9 ± 79.5 in patients who received 360 mg RPC4046 (P < .0001) compared with a reduction of 4.4 ± 59.9 in patients who received placebo. The 360-mg RPC4046 group, compared with the placebo group, showed significant reductions in validated endoscopic severity score at all esophageal locations (P < .0001), validated histologic grade and stage scores (both P < .0001), and clinician's global assessment of disease severity (P = .0352); they had a numerical reduction in scores from the dysphagia symptom diary (P = .0733). Significant reductions in esophageal eosinophil counts and histologic and endoscopic features were observed in patients with steroid-refractory EoE who received RPC4046. The most common adverse events were headache and upper respiratory tract infection.In a phase 2 trial of patients with EoE, we found RPC4046 (a monoclonal antibody against IL13) to reduce histologic and endoscopic features compared with placebo. RPC4046 was well tolerated. ClinicalTrials.gov no: NCT02098473.

View details for DOI 10.1053/j.gastro.2018.10.051

View details for Web of Science ID 000457714300022

View details for PubMedID 30395812