Document Detail

Theoretical analysis of efficacy of biological agent for rheumatoid arthritis based on target molecular binding occupancy.
MedLine Citation:
PMID:  23300004     Owner:  NLM     Status:  Publisher    
Recently, biological agents have been used for treatment of rheumatoid arthritis (RA), though the standard therapeutic doses vary among the agents utilized. To investigate the mechanisms related to those differences, we theoretically analyzed the target molecular binding occupancies of 4 biological agents: tocilizumab, infliximab, adalimumab, and etanercept. The average binding occupancy to the target molecule (Φ(ss)) was estimated to be 99.50 ± 0.44 % in a steady state after administration of the standard therapeutic dose of each agent. Furthermore, achieved American College of Rheumatology (ACR) 20, used as an index of clinical efficacy, increased in correlation with the value for Φ(ss). These results suggest that clinical effects are achieved with a high value of target molecular binding occupancy. Thus, we considered that all of the agents examined in this study are antagonists and elicit clinical efficacy by inhibiting the signaling of biologically active substances that are not necessary for life maintenance and are secreted or released specifically in pathological conditions. In addition, target molecular binding occupancy can be used as an appropriate index for evaluating the standard therapeutic dose of biological agent for RA.
Kanae Tani; Risa Takayanagi; Haruko Yokoyama; Yasuhiko Yamada
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-9
Journal Detail:
Title:  Rheumatology international     Volume:  -     ISSN:  1437-160X     ISO Abbreviation:  Rheumatol. Int.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8206885     Medline TA:  Rheumatol Int     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Clinical Evaluation of Drug Efficacy, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.
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