Journal ArticleDOI
Intraarticular sprifermin (recombinant human fibroblast growth factor 18) in knee osteoarthritis: a randomized, double-blind, placebo-controlled trial.
L. Stefan Lohmander,L. Stefan Lohmander,Scarlett Hellot,Don Dreher,Eduard F. W. Krantz,Dawie S. Kruger,Ali Guermazi,Felix Eckstein +7 more
TLDR
To evaluate the efficacy and safety of intraarticular sprifermin (recombinant human fibroblast growth factor 18) in the treatment of symptomatic knee osteoarthritis (OA).Abstract:
Objective. We evaluated in a proof-of-concept double-blind placebo-controlled randomized trial the efficacy and safety of intra-articular sprifermin (recombinant human fibroblast growth factor 18) in patients with symptomatic knee OA. Methods. Sprifermin was evaluated as intra-articular injection at 10, 30, and 100μg. Primary efficacy endpoint was change in central medial femorotibial compartment (cMFTC) cartilage thickness at 6 and 12 months using quantitative MRI (qMRI). Primary safety endpoints were nature, incidence and severity of local and systemic treatment-emergent adverse events, acute inflammatory reactions and laboratory assessments. Secondary endpoints included changes in total and compartment femorotibial cartilage thickness and volume by qMRI, joint space width (JSW) from radiographs, and Western Ontario McMaster Universities (WOMAC) pain. Results. 192 patients were randomized and evaluated for safety, 180 completed the trial, 168 evaluated for primary efficacy endpoint. We found no statistically significant dose-response in change in cMFTC 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 improved in WOMAC pain, with statistically significant less improvement at 12 months in patients receiving 100μg sprifermin than placebo. There was no significant difference in SAEs, TEAEs, AIRs between sprifermin and placebo groups. Conclusion. There was no statistically significant relationship between treatment group and reduction in cMFTC cartilage thickness. However, pre-specified structural secondary endpoints showed statistically significant dose-dependent reductions following sprifermin treatment. Sprifermin was not associated with any local or systemic safety concerns. Clinicaltrials.gov identification: NCT01033994. © 2014 American College of Rheumatology. (Less)read more
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Journal ArticleDOI
Current research on pharmacologic and regenerative therapies for osteoarthritis.
TL;DR: Current research focuses on the development of new OA drugs (such as sprifermin/recombinant human fibroblast growth factor-18, tanezumab/monoclonal antibody against β-nerve growth factor), which aims for more effectiveness and less incidence of adverse effects than the traditional ones.
Journal ArticleDOI
MSC exosome as a cell-free MSC therapy for cartilage regeneration: Implications for osteoarthritis treatment.
TL;DR: The current understanding of MSC exosomes is reviewed, the possible mechanisms of action in cartilage repair are discussed, and new perspectives for development of an off-the-shelf and cell-free MSC therapy for treatment of cartilage injuries and osteoarthritis are provided.
Journal ArticleDOI
FGF/FGFR signaling in health and disease
Yangli Xie,Nan Su,Jing Yang,Qiaoyan Tan,Shuo Huang,Min Jin,Zhenhong Ni,Bin Zhang,Dali Zhang,Fengtao Luo,Hangang Chen,Xianding Sun,Jian Q. Feng,Huabing Qi,Lin Chen +14 more
TL;DR: A comprehensive overview of the current understanding of FGF signaling and its roles in organ development, injury repair, and the pathophysiology of spectrum of diseases, which is a consequence of F GF signaling dysregulation, is provided.
Journal ArticleDOI
Disease-modifying treatments for osteoarthritis (DMOADs) of the knee and hip: lessons learned from failures and opportunities for the future
Morten A. Karsdal,M. Michaelis,Christoph Ladel,Anne Sofie Siebuhr,Asger Reinstrup Bihlet,Jeppe Ragnar Andersen,Hans Guehring,C. Christiansen,Anne-Christine Bay-Jensen,Virginia B. Kraus +9 more
TL;DR: This review of several ambitious but failed attempts to develop joint structure-modifying treatments for OA suggests that these failures arose from unrealistic hypotheses, sub-optimal selection of patient populations or drug dose, and/or inadequate sensitivity of the trial endpoints.
Journal ArticleDOI
Intra-articular treatment options for knee osteoarthritis
TL;DR: Current and future intra-articular therapies for knee OA are critically appraise and generally positive efficacy conclusions concerning mesenchymal ‘stem’ cell therapy for knee cartilage pathology might be overstated owing to selective outcome reporting.
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Schwebel,James Scott,Maria Segui-Gomez,Saeid Shahraz,Donald S. Shepard,Hwashin Shin,Rupak Shivakoti,Donald H. Silberberg,David Singh,Gitanjali M Singh,Jasvinder A. Singh,Jessica Singleton,David A. Sleet,Karen Sliwa,Emma Smith,Jennifer L. Smith,Nicolas J. C. Stapelberg,Andrew C Steer,Timothy J. Steiner,Wilma A. Stolk,Lars Jacob Stovner,Christopher R. Sudfeld,Sana Syed,Giorgio Tamburlini,Mohammad Tavakkoli,Hugh R. Taylor,Jennifer A. Taylor,William J. Taylor,Bernadette Thomas,W. Murray Thomson,George D. Thurston,Imad M. Tleyjeh,Marcello Tonelli,Jeffrey A. Towbin,Thomas Truelsen,Miltiadis K. Tsilimbaris,Clotilde Ubeda,Eduardo A. Undurraga,Marieke J. van der Werf,Jim van Os,Monica S. Vavilala,Narayanaswamy Venketasubramanian,Mengru Wang,Wenzhi Wang,Kerrianne Watt,David Weatherall,Martin A. Weinstock,Robert G. Weintraub,Marc G. Weisskopf,Myrna M. Weissman,Richard A. White,Harvey Whiteford,Steven T. Wiersma,James D. Wilkinson,Hywel C Williams,Sean R.M. Williams,Emma Witt,Frederick Wolfe,Anthony D. Woolf,Sarah Wulf,Pon Hsiu Yeh,Anita K. M. Zaidi,Zhi Jie Zheng,David Zonies,Alan D. Lopez,Christopher J L Murray +363 more
TL;DR: Prevalence and severity of health loss were weakly correlated and age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010, but population growth and ageing have increased YLD numbers and crude rates over the past two decades.
Journal ArticleDOI
Development of criteria for the classification and reporting of osteoarthritis: Classification of osteoarthritis of the knee
Roy D. Altman,E. Asch,Daniel Bloch,Giles G. Bole,David G. Borenstein,Kenneth D. Brandt,Wallace C. Christy,Cooke Td,Robert A. Greenwald,Marc C. Hochberg,David S. Howell,David L. Kaplan,William J. Koopman,Selden Longley,Henry J. Mankin,Dennis J. McShane,Thomas A. Medsger,Robert F. Meenan,William M. Mikkelsen,Roland W. Moskowitz,William A. Murphy,B. Rothschild,Mark R. Segal,Leon Sokoloff,Frederick Wolfe +24 more
TL;DR: Variables from the medical history, physical examination, laboratory tests, and radiographs were used to develop sets of criteria that serve different investigative purposes and these proposed criteria utilize classification trees, or algorithms.
Journal ArticleDOI
American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee
Marc C. Hochberg,Roy D. Altman,Karine Toupin April,Maria Benkhalti,Gordon H. Guyatt,Jessie McGowan,Tanveer Towheed,Vivian Welch,George A. Wells,Peter Tugwell +9 more
TL;DR: To update the American College of Rheumatology (ACR) 2000 recommendations for hip and knee osteoarthritis (OA) and develop new recommendations for hand OA.