Translational strategies in drug development for knee osteoarthritis

被引：11

作者：

Cowan, Kyra J. ^{[1
]}

Kleinschmidt-Doerr, Kerstin ^{[1
]}

Gigout, Anne ^{[1
]}

Moreau, Flavie ^{[2
]}

Kraines, Jeff ^{[2
]}

Townsend, Robert ^{[2
]}

Dolgos, Hugues ^{[3
]}

DeMartino, Julie ^{[2
]}

机构：

[1] Merck KGaA, Darmstadt, Germany

[2] EMD Serono Res & Dev Inst, Billerica, MA USA

[3] Servier, Suresnes, France

来源：

DRUG DISCOVERY TODAY | 2020年 / 25卷 / 06期

关键词：

FIBROBLAST-GROWTH-FACTOR; POST-HOC ANALYSIS; INTRAARTICULAR SPRIFERMIN; CARTILAGE THICKNESS; CLINICAL PHENOTYPES; BIOCHEMICAL MARKERS; PLACEBO; HIP; METABOLISM; MANAGEMENT;

D O I：

10.1016/j.drudis.2020.03.015

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Osteoarthritis (OA) is a common disease worldwide with large unmet medical needs. To bring innovative treatments to OA patients, we at Merck have implemented a comprehensive strategy for drug candidate evaluation. We have a clear framework for decision-making in our preclinical pipeline, to design our clinical proof-of-concept trials for OA patients. We have qualified our strategy to define and refine dose and dosing regimen, for treatments administered either systemically or intra-articularly (IA). We do this through preclinical in vitro and in vivo studies, and by back-translating results from clinical studies in OA patients.

引用

页码：1054 / 1064

页数：11

共 67 条

[1] Leptin in the interplay of inflammation, metabolism and immune system disorders
Abella, Vanessa
Scotece, Morena
Conde, Javier
Pino, Jesus
Angel Gonzalez-Gay, Miguel
Gomez-Reino, Juan J.
Mera, Antonio
Lago, Francisca
Gomez, Rodolfo
Gualillo, Oreste
[J]. NATURE REVIEWS RHEUMATOLOGY, 2017, 13 (02) : 100 - 109
[2] A randomised controlled trial of tidal irrigation vs corticosteroid injection in knee osteoarthritis: the KIVIS Study
Arden, N. K.
Reading, I. C.
Jordan, K. M.
Thomas, L.
Platten, H.
Hassan, A.
Ledingham, J.
[J]. OSTEOARTHRITIS AND CARTILAGE, 2008, 16 (06) : 733 - 739
[3] Arthritis Foundation, 2017, 2017 PAT FOC DRUG DE
[4] OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis
Bannuru, R. R.
Osani, M. C.
Vaysbrot, E. E.
Arden, N. K.
Bennell, K.
Bierma-Zeinstra, S. M. A.
Kraus, V. B.
Lohmander, L. S.
Abbott, J. H.
Bhandari, M.
Blanco, F. J.
Espinosa, R.
Haugen, I. K.
Lin, J.
Mandl, L. A.
Moilanen, E.
Nakamura, N.
Snyder-Mackler, L.
Trojian, T.
Underwood, M.
McAlindon, T. E.
[J]. OSTEOARTHRITIS AND CARTILAGE, 2019, 27 (11) : 1578 - 1589
[5] Biochemical markers of type II collagen breakdown and synthesis are positioned at specific sites in human osteoarthritic knee cartilage
Bay-Jensen, A. -C.
Andersen, T. L.
Tabassi, N. Charni-Ben
Kristensen, P. W.
Kjaersgaard-Andersen, P.
Sandell, L.
Garnero, P.
Delaisse, J. -M.
[J]. OSTEOARTHRITIS AND CARTILAGE, 2008, 16 (05) : 615 - 623
[6] Biochemical marker discovery, testing and evaluation for facilitating OA drug discovery and development
Bay-Jensen, Anne-Christine
Thudium, Christian S.
Gualillo, Oreste
Molasheri, Ali
[J]. DRUG DISCOVERY TODAY, 2018, 23 (02) : 349 - 358
[7] SPONTANEOUS HOME CAGE ACTIVITY IS SENSITIVE TO ANTI-NGF TREATMENT OR CAN BE LINKED TO JOINT STIFFNESS IN DIFFERENT MODELS OF SURGERY-INDUCED OSTEOARTHRITIS
Brenneis, C.
Westhof, A.
Duschek, J.
Chang, Y. -M.
Pitsillides, A. A.
Michaelis, M.
Kleinschmidt, K.
Guehring, H.
[J]. OSTEOARTHRITIS AND CARTILAGE, 2016, 24 : S498 - S499
[8] Brenneis C, 2017, J AM ASSOC LAB ANIM, V56, P18
[9] Characterization of synovial fluid metabolomic phenotypes of cartilage morphological changes associated with osteoarthritis
Carlson, A. K.
Rawle, R. A.
Wallace, C. W.
Brooks, E. G.
Adams, E.
Greenwood, M. C.
Olmer, M.
Lotz, M. K.
Bothner, B.
June, R. K.
[J]. OSTEOARTHRITIS AND CARTILAGE, 2019, 27 (08) : 1174 - 1184
[10] PENALIZED LINEAR DISCRIMINANT ANALYSIS REVEALS DIVERGENT GAIT PATTERNS IN THREE SURGICALLY-INDUCED OA MODELS
Chang, Y-M.
Marsh-Dougerthy, J.
Brenneis, C.
Kleinschmidt, K.
Michaelis, M.
Guehring, H.
Piles, M.
Pitsillides, A. A.
[J]. OSTEOARTHRITIS AND CARTILAGE, 2016, 24 : S107 - S108

← 1 2 3 4 5 6 7 →