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LY2439821, a humanized anti-interleukin-17 monoclonal antibody, in the treatment of patients with rheumatoid arthritis a phase I randomized, double-blind, placebo-controlled, proof-of-concept study

MC Genovese, Filip Van den Bosch UGent, SA Roberson, S Bojin, IM Biagini, Peter Ryan and J Sloan-Lancaster (2010) ARTHRITIS AND RHEUMATISM. 62(4). p.929-939
abstract
Objective. We undertook this study to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of LY2439821, a humanized anti-interleukin-17 (anti-IL-17) monoclonal antibody, in a first in-human trial in rheumatoid arthritis (RA) patients taking oral disease-modifying antirheumatic drugs (DMARDs). Methods. This randomized, double-blind, placebo-controlled study consisted of 2 parts. In part A, 20 patients received 1 intravenous (IV) dose of LY2439821 (0.06, 0.2, 0.6, or 2.0 mg/kg, escalating) or placebo followed by 8 weeks of evaluation. End points included safety, tolerability, and pharmacokinetics. In part B, 77 patients received 1 IV dose of LY2439821 (0.2, 0.6, or 2.0 mg/kg) or placebo every 2 weeks for a total of 5 doses, with a total evaluation period of 16 weeks. End points included safety, tolerability, pharmacokinetics/pharmacodynamics, and efficacy (Disease Activity Score in 28 joints [DAS28] and percentages of patients meeting American College of Rheumatology 20%, 50%, or 70% improvement criteria [achieving an ACR20, ACR50, or ACR70 response]). The primary efficacy end point was the DAS28 at week 10. Results. Baseline characteristics were similar across all groups. Changes in the DAS28 were significantly greater in the 0.2 mg/kg, 2.0 mg/kg, and all-LY2439821-combined groups (-2.3, -2.4, and -2.3, respectively) than in the placebo group (-1.7) at week 10 (P <= 0.05), and these differences were significant as early as week 1. Percentages of ACR20, ACR50, and ACR70 responses as well as improvements in the ACR core set of measures were greater in LY2439821-treated patients than in placebo-treated patients at multiple time points. There was no apparent dose-response relationship in treatment-emergent adverse events. Conclusion. LY2439821 added to oral DMARDs improved signs and symptoms of RA, with no strong adverse safety signal noted. This first evaluation of LY2439821 supports neutralization of IL-17 as a potential novel goal for the treatment of RA.
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author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
INTERLEUKIN-17, EXPRESSION, T-CELLS, REVISED CRITERIA, COLONY-STIMULATING FACTOR, CLASSIFICATION, INFLAMMATION, ASSOCIATION, REQUIREMENT
journal title
ARTHRITIS AND RHEUMATISM
Arthritis Rheum.
volume
62
issue
4
pages
929 - 939
Web of Science type
Article
Web of Science id
000279432300003
JCR category
RHEUMATOLOGY
JCR impact factor
8.435 (2010)
JCR rank
2/29 (2010)
JCR quartile
1 (2010)
ISSN
0004-3591
DOI
10.1002/art.27334
language
English
UGent publication?
yes
classification
A1
id
1095406
handle
http://hdl.handle.net/1854/LU-1095406
date created
2011-01-07 09:32:07
date last changed
2016-12-19 15:41:27
@article{1095406,
  abstract     = {Objective. We undertook this study to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of LY2439821, a humanized anti-interleukin-17 (anti-IL-17) monoclonal antibody, in a first in-human trial in rheumatoid arthritis (RA) patients taking oral disease-modifying antirheumatic drugs (DMARDs).
Methods. This randomized, double-blind, placebo-controlled study consisted of 2 parts. In part A, 20 patients received 1 intravenous (IV) dose of LY2439821 (0.06, 0.2, 0.6, or 2.0 mg/kg, escalating) or placebo followed by 8 weeks of evaluation. End points included safety, tolerability, and pharmacokinetics. In part B, 77 patients received 1 IV dose of LY2439821 (0.2, 0.6, or 2.0 mg/kg) or placebo every 2 weeks for a total of 5 doses, with a total evaluation period of 16 weeks. End points included safety, tolerability, pharmacokinetics/pharmacodynamics, and efficacy (Disease Activity Score in 28 joints [DAS28] and percentages of patients meeting American College of Rheumatology 20\%, 50\%, or 70\% improvement criteria [achieving an ACR20, ACR50, or ACR70 response]). The primary efficacy end point was the DAS28 at week 10.
Results. Baseline characteristics were similar across all groups. Changes in the DAS28 were significantly greater in the 0.2 mg/kg, 2.0 mg/kg, and all-LY2439821-combined groups (-2.3, -2.4, and -2.3, respectively) than in the placebo group (-1.7) at week 10 (P {\textlangle}= 0.05), and these differences were significant as early as week 1. Percentages of ACR20, ACR50, and ACR70 responses as well as improvements in the ACR core set of measures were greater in LY2439821-treated patients than in placebo-treated patients at multiple time points. There was no apparent dose-response relationship in treatment-emergent adverse events.
Conclusion. LY2439821 added to oral DMARDs improved signs and symptoms of RA, with no strong adverse safety signal noted. This first evaluation of LY2439821 supports neutralization of IL-17 as a potential novel goal for the treatment of RA.},
  author       = {Genovese, MC and Van den Bosch, Filip and Roberson, SA and Bojin, S and Biagini, IM and Ryan, Peter and Sloan-Lancaster, J},
  issn         = {0004-3591},
  journal      = {ARTHRITIS AND RHEUMATISM},
  keyword      = {INTERLEUKIN-17,EXPRESSION,T-CELLS,REVISED CRITERIA,COLONY-STIMULATING FACTOR,CLASSIFICATION,INFLAMMATION,ASSOCIATION,REQUIREMENT},
  language     = {eng},
  number       = {4},
  pages        = {929--939},
  title        = {LY2439821, a humanized anti-interleukin-17 monoclonal antibody, in the treatment of patients with rheumatoid arthritis a phase I randomized, double-blind, placebo-controlled, proof-of-concept study},
  url          = {http://dx.doi.org/10.1002/art.27334},
  volume       = {62},
  year         = {2010},
}

Chicago
Genovese, MC, Filip Van den Bosch, SA Roberson, S Bojin, IM Biagini, Peter Ryan, and J Sloan-Lancaster. 2010. “LY2439821, a Humanized Anti-interleukin-17 Monoclonal Antibody, in the Treatment of Patients with Rheumatoid Arthritis a Phase I Randomized, Double-blind, Placebo-controlled, Proof-of-concept Study.” Arthritis and Rheumatism 62 (4): 929–939.
APA
Genovese, M., Van den Bosch, F., Roberson, S., Bojin, S., Biagini, I., Ryan, P., & Sloan-Lancaster, J. (2010). LY2439821, a humanized anti-interleukin-17 monoclonal antibody, in the treatment of patients with rheumatoid arthritis a phase I randomized, double-blind, placebo-controlled, proof-of-concept study. ARTHRITIS AND RHEUMATISM, 62(4), 929–939.
Vancouver
1.
Genovese M, Van den Bosch F, Roberson S, Bojin S, Biagini I, Ryan P, et al. LY2439821, a humanized anti-interleukin-17 monoclonal antibody, in the treatment of patients with rheumatoid arthritis a phase I randomized, double-blind, placebo-controlled, proof-of-concept study. ARTHRITIS AND RHEUMATISM. 2010;62(4):929–39.
MLA
Genovese, MC, Filip Van den Bosch, SA Roberson, et al. “LY2439821, a Humanized Anti-interleukin-17 Monoclonal Antibody, in the Treatment of Patients with Rheumatoid Arthritis a Phase I Randomized, Double-blind, Placebo-controlled, Proof-of-concept Study.” ARTHRITIS AND RHEUMATISM 62.4 (2010): 929–939. Print.