Intraarticular Sprifermin (Recombinant Human Fibroblast Growth Factor 18) in Knee Osteoarthritis: A Randomized, Double‐Blind, Placebo‐Controlled Trial

Arthritis and Rheumatology - Tập 66 Số 7 - Trang 1820-1831 - 2014
Stefan Lohmander1,2, Scarlett Hellot3, Don Dreher4, Eduard F. W. Krantz5, Dawie Kruger6, Ali Guermazi7, F. Eckstein8,9
1Lund University, Lund, Sweden
2University of Southern Denmark, Odense, Denmark
3Merck Serono, Geneva, Switzerland
4Totzke & Dreher Scientific Geneva Switzerland
5Farmovs‐Parexel Bloemfontein South Africa
6Parexel Early Phase George South Africa
7Boston University School of Medicine and Boston Imaging Core Lab Boston Massachusetts
8Chondrometrics Ainring Germany
9Paracelsus Medical University, Salzburg, Austria

Tóm tắt

ObjectiveTo evaluate the efficacy and safety of intraarticular sprifermin (recombinant human fibroblast growth factor 18) in the treatment of symptomatic knee osteoarthritis (OA).MethodsThe study was a randomized, double‐blind, placebo‐controlled, proof‐of‐concept trial. Intraarticular sprifermin was evaluated at doses of 10 μg, 30 μg, and 100 μg. The primary efficacy end point was change in central medial femorotibial compartment cartilage thickness at 6 months and 12 months as determined using quantitative magnetic resonance imaging (qMRI). The primary safety end points were nature, incidence, and severity of local and systemic treatment‐emergent adverse events (AEs) and acute inflammatory reactions, as well as results of laboratory assessments. Secondary end points included changes in total and compartment femorotibial cartilage thickness and volume as assessed by qMRI, changes in joint space width (JSW) seen on radiographs, and pain scores on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).ResultsOne hundred ninety‐two patients were randomized and evaluated for safety, 180 completed the trial, and 168 were evaluated for the primary efficacy end point. We found no statistically significant dose response in change in central medial femorotibial compartment cartilage thickness. Sprifermin was associated with statistically significant, dose‐dependent reductions in loss of total and lateral femorotibial cartilage thickness and volume and in JSW narrowing in the lateral femorotibial compartment. All groups had improved WOMAC pain scores, with statistically significantly less improvement at 12 months in patients receiving the 100‐μg dose of sprifermin as compared with those receiving placebo. There was no significant difference in serious AEs, treatment‐emergent AEs, or acute inflammatory reactions between sprifermin and placebo groups.ConclusionNo statistically significant relationship between treatment group and reduction in central medial femorotibial compartment cartilage thickness was observed; however, prespecified structural secondary end points showed statistically significant dose‐dependent reductions after sprifermin treatment. Sprifermin was not associated with any local or systemic safety concerns.

Từ khóa


Tài liệu tham khảo

10.1016/S0140-6736(12)61729-2

10.1186/ar2531

10.1002/acr.21898

10.1016/j.joca.2010.01.013

10.1002/acr.21596

10.1002/1529-0131(200111)44:11<2539::AID-ART434>3.0.CO;2-T

10.1016/S0140-6736(00)03610-2

10.1001/archinte.162.18.2113

10.1002/art.21122

10.1002/art.22160

10.1002/art.24255

10.1136/annrheumdis-2012-202231

10.1136/annrheumdis-2012-202239

10.1038/nrrheum.2010.178

10.1053/joca.2002.0514

10.1016/j.joca.2005.03.003

Gigout A, 2012, Intermittent but not continuous exposure to recombinant human fibroblast growth factor‐18 (rhFGF18) promotes chondrocyte anabolism and phenotype in 3D culture, Cartilage, 3, 167

10.1016/j.joca.2012.02.182

10.1016/S1063-4584(11)60336-1

10.1038/nrrheum.2012.113

10.1002/art.1780290816

10.1136/ard.16.4.494

Bellamy N, 1988, Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee, J Rheumatol, 15, 1833

10.1016/j.joca.2008.07.008

10.1002/acr.20370

10.1136/annrheumdis-2011-201164

10.1007/s00330-004-2312-6

10.1016/j.joca.2003.11.003

10.1016/j.joca.2012.07.012

10.1002/1529-0131(200109)44:9<2072::AID-ART357>3.0.CO;2-3

10.1002/art.20191

10.1136/ard.2007.076919

10.1016/j.joca.2006.03.005

10.1109/TMI.2007.907323

10.1002/art.21348

10.1016/j.joca.2006.11.009

10.1016/j.joca.2010.10.022

10.1016/j.joca.2010.10.029

10.1016/j.joca.2010.10.030

10.1136/ard.2008.088732

10.1136/ard.2010.140848

10.1136/ard.2008.089904

10.1016/j.joca.2012.09.012

10.1136/ard.2010.142364

10.1002/art.24208

10.1002/art.37987

10.1002/1529-0131(200108)45:4<384::AID-ART352>3.0.CO;2-0

10.1016/j.joca.2006.09.001

10.1016/j.joca.2009.04.009

Thông tin
Thông tin xuất bản

Arthritis and Rheumatology

Tập 66 Số 7

1820-1831

Thông tin tác giả