TY - JOUR
T1 - Efficacy and Safety of E6011, an Anti-Fractalkine Monoclonal Antibody, in Patients With Active Rheumatoid Arthritis With Inadequate Response to Methotrexate
T2 - Results of a Randomized, Double-Blind, Placebo-Controlled Phase II Study
AU - Tanaka, Yoshiya
AU - Takeuchi, Tsutomu
AU - Yamanaka, Hisashi
AU - Nanki, Toshihiro
AU - Umehara, Hisanori
AU - Yasuda, Nobuyuki
AU - Tago, Fumitoshi
AU - Kitahara, Yasumi
AU - Kawakubo, Makoto
AU - Torii, Kentaro
AU - Hojo, Seiichiro
AU - Kawano, Tetsu
AU - Imai, Toshio
N1 - Funding Information:
This work was supported by funding from Eisai Company, Ltd. Eisai Company, Ltd. was involved in study design, data collection, analysis, and interpretation of data. The corresponding author had full access to all data and had responsibility for the decision to submit for publication. Publication of this article was not contingent upon approval by Eisai Company, Ltd.
Publisher Copyright:
© 2020 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.
PY - 2021/4
Y1 - 2021/4
N2 - Objective: To evaluate the efficacy and safety of E6011, a humanized IgG2 monoclonal antibody against human fractalkine (FKN), in a phase II, double-blind, placebo-controlled study in rheumatoid arthritis (RA) patients. Methods: Patients with moderate-to-severe RA who had an inadequate response to methotrexate were randomly assigned to a placebo group or to E6011 100-mg, 200-mg, or 400/200-mg groups at a 2:1:2:2 ratio. During the 24-week period, patients received the study drug subcutaneously at weeks 0, 1, and 2 and then once every 2 weeks. The primary end point was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 12. Results: Study drugs were administered to 190 patients (placebo, n = 54; E6011 100 mg, n = 28; E6011 200 mg, n = 54; E6011 400/200 mg, n = 54), and 169 patients completed treatment. A significant difference from placebo was not found in ACR20 response rates at week 12 (37.0% [placebo], 39.3% [100 mg], 48.1% [200 mg], and 46.3% [400/200 mg], using nonresponder imputation). As a secondary end point, ACR20 response rate in the 200-mg and 400/200-mg groups attained statistical significance at week 24 (35.2% [placebo], 39.3% [100 mg], 53.7% [200 mg], and 57.4% [400/200 mg]). Subsequent exploratory subgroup analysis revealed greater efficacy of E6011, particularly in patients with a higher baseline proportion of CD16+ monocytes; ACR20 response rates in this patient subgroup at week 24 were 30.0% (placebo), 46.7% (100 mg), 57.7% (200 mg), and 69.6% (400/200 mg). E6011 administered for 24 weeks was well tolerated. Conclusion: This is the first evidence that E6011, a novel cell trafficking inhibitor targeting the FKN–CX3CR1 interaction, is modestly effective with 24 weeks of treatment in RA patients, although the primary end point was not met.
AB - Objective: To evaluate the efficacy and safety of E6011, a humanized IgG2 monoclonal antibody against human fractalkine (FKN), in a phase II, double-blind, placebo-controlled study in rheumatoid arthritis (RA) patients. Methods: Patients with moderate-to-severe RA who had an inadequate response to methotrexate were randomly assigned to a placebo group or to E6011 100-mg, 200-mg, or 400/200-mg groups at a 2:1:2:2 ratio. During the 24-week period, patients received the study drug subcutaneously at weeks 0, 1, and 2 and then once every 2 weeks. The primary end point was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 12. Results: Study drugs were administered to 190 patients (placebo, n = 54; E6011 100 mg, n = 28; E6011 200 mg, n = 54; E6011 400/200 mg, n = 54), and 169 patients completed treatment. A significant difference from placebo was not found in ACR20 response rates at week 12 (37.0% [placebo], 39.3% [100 mg], 48.1% [200 mg], and 46.3% [400/200 mg], using nonresponder imputation). As a secondary end point, ACR20 response rate in the 200-mg and 400/200-mg groups attained statistical significance at week 24 (35.2% [placebo], 39.3% [100 mg], 53.7% [200 mg], and 57.4% [400/200 mg]). Subsequent exploratory subgroup analysis revealed greater efficacy of E6011, particularly in patients with a higher baseline proportion of CD16+ monocytes; ACR20 response rates in this patient subgroup at week 24 were 30.0% (placebo), 46.7% (100 mg), 57.7% (200 mg), and 69.6% (400/200 mg). E6011 administered for 24 weeks was well tolerated. Conclusion: This is the first evidence that E6011, a novel cell trafficking inhibitor targeting the FKN–CX3CR1 interaction, is modestly effective with 24 weeks of treatment in RA patients, although the primary end point was not met.
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U2 - 10.1002/art.41555
DO - 10.1002/art.41555
M3 - Article
C2 - 33038062
AN - SCOPUS:85101294047
SN - 2326-5191
VL - 73
SP - 587
EP - 595
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
IS - 4
ER -