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Efficacy and Safety of E6011, an Anti‐Fractalkine Monoclonal Antibody, in Patients With Active Rheumatoid Arthritis With Inadequate Response to Methotrexate: Results of a Randomized, Double‐Blind, Placebo‐Controlled Phase II Study

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 m...

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Autores principales: Tanaka, Yoshiya, Takeuchi, Tsutomu, Yamanaka, Hisashi, Nanki, Toshihiro, Umehara, Hisanori, Yasuda, Nobuyuki, Tago, Fumitoshi, Kitahara, Yasumi, Kawakubo, Makoto, Torii, Kentaro, Hojo, Seiichiro, Kawano, Tetsu, Imai, Toshio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048525/
https://www.ncbi.nlm.nih.gov/pubmed/33038062
http://dx.doi.org/10.1002/art.41555
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author Tanaka, Yoshiya
Takeuchi, Tsutomu
Yamanaka, Hisashi
Nanki, Toshihiro
Umehara, Hisanori
Yasuda, Nobuyuki
Tago, Fumitoshi
Kitahara, Yasumi
Kawakubo, Makoto
Torii, Kentaro
Hojo, Seiichiro
Kawano, Tetsu
Imai, Toshio
author_facet Tanaka, Yoshiya
Takeuchi, Tsutomu
Yamanaka, Hisashi
Nanki, Toshihiro
Umehara, Hisanori
Yasuda, Nobuyuki
Tago, Fumitoshi
Kitahara, Yasumi
Kawakubo, Makoto
Torii, Kentaro
Hojo, Seiichiro
Kawano, Tetsu
Imai, Toshio
author_sort Tanaka, Yoshiya
collection PubMed
description 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–CX(3)CR1 interaction, is modestly effective with 24 weeks of treatment in RA patients, although the primary end point was not met.
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spelling pubmed-80485252021-04-16 Efficacy and Safety of E6011, an Anti‐Fractalkine Monoclonal Antibody, in Patients With Active Rheumatoid Arthritis With Inadequate Response to Methotrexate: Results of a Randomized, Double‐Blind, Placebo‐Controlled Phase II Study Tanaka, Yoshiya Takeuchi, Tsutomu Yamanaka, Hisashi Nanki, Toshihiro Umehara, Hisanori Yasuda, Nobuyuki Tago, Fumitoshi Kitahara, Yasumi Kawakubo, Makoto Torii, Kentaro Hojo, Seiichiro Kawano, Tetsu Imai, Toshio Arthritis Rheumatol Rheumatoid Arthritis 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–CX(3)CR1 interaction, is modestly effective with 24 weeks of treatment in RA patients, although the primary end point was not met. John Wiley and Sons Inc. 2021-02-18 2021-04 /pmc/articles/PMC8048525/ /pubmed/33038062 http://dx.doi.org/10.1002/art.41555 Text en © 2020 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Rheumatoid Arthritis
Tanaka, Yoshiya
Takeuchi, Tsutomu
Yamanaka, Hisashi
Nanki, Toshihiro
Umehara, Hisanori
Yasuda, Nobuyuki
Tago, Fumitoshi
Kitahara, Yasumi
Kawakubo, Makoto
Torii, Kentaro
Hojo, Seiichiro
Kawano, Tetsu
Imai, Toshio
Efficacy and Safety of E6011, an Anti‐Fractalkine Monoclonal Antibody, in Patients With Active Rheumatoid Arthritis With Inadequate Response to Methotrexate: Results of a Randomized, Double‐Blind, Placebo‐Controlled Phase II Study
title Efficacy and Safety of E6011, an Anti‐Fractalkine Monoclonal Antibody, in Patients With Active Rheumatoid Arthritis With Inadequate Response to Methotrexate: Results of a Randomized, Double‐Blind, Placebo‐Controlled Phase II Study
title_full Efficacy and Safety of E6011, an Anti‐Fractalkine Monoclonal Antibody, in Patients With Active Rheumatoid Arthritis With Inadequate Response to Methotrexate: Results of a Randomized, Double‐Blind, Placebo‐Controlled Phase II Study
title_fullStr Efficacy and Safety of E6011, an Anti‐Fractalkine Monoclonal Antibody, in Patients With Active Rheumatoid Arthritis With Inadequate Response to Methotrexate: Results of a Randomized, Double‐Blind, Placebo‐Controlled Phase II Study
title_full_unstemmed Efficacy and Safety of E6011, an Anti‐Fractalkine Monoclonal Antibody, in Patients With Active Rheumatoid Arthritis With Inadequate Response to Methotrexate: Results of a Randomized, Double‐Blind, Placebo‐Controlled Phase II Study
title_short Efficacy and Safety of E6011, an Anti‐Fractalkine Monoclonal Antibody, in Patients With Active Rheumatoid Arthritis With Inadequate Response to Methotrexate: Results of a Randomized, Double‐Blind, Placebo‐Controlled Phase II Study
title_sort efficacy and safety of e6011, an anti‐fractalkine monoclonal antibody, in patients with active rheumatoid arthritis with inadequate response to methotrexate: results of a randomized, double‐blind, placebo‐controlled phase ii study
topic Rheumatoid Arthritis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048525/
https://www.ncbi.nlm.nih.gov/pubmed/33038062
http://dx.doi.org/10.1002/art.41555
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