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Structural effects of sprifermin in knee osteoarthritis : a post-hoc analysis on cartilage and non-cartilaginous tissue alterations in a randomized controlled trial

Roemer, Frank W.; Aydemir, Aida; Lohmander, Stefan LU ; Crema, Michel D.; Marra, Monica Dias; Muurahainen, Norma; Felson, David T.; Eckstein, Felix and Guermazi, Ali (2016) In BMC Musculoskeletal Disorders 17(1). p.1-7
Abstract

Background: A recent publication on efficacy of Sprifermin for knee osteoarthritis (OA) using quantitatively MRI-defined central medial tibio-femoral compartment cartilage thickness as the structural primary endpoint reported no statistically significant dose response. However, Sprifermin was associated with statistically significant, dose-dependent reductions in loss of total and lateral tibio-femoral cartilage thickness. Based on these preliminary promising data a post-hoc analysis of secondary assessment and endpoints was performed to evaluate potential effects of Sprifermin on semi-quantitatively evaluated structural MRI parameters. Aim of the present analysis was to determine effects of sprifermin on several knee joint tissues over... (More)

Background: A recent publication on efficacy of Sprifermin for knee osteoarthritis (OA) using quantitatively MRI-defined central medial tibio-femoral compartment cartilage thickness as the structural primary endpoint reported no statistically significant dose response. However, Sprifermin was associated with statistically significant, dose-dependent reductions in loss of total and lateral tibio-femoral cartilage thickness. Based on these preliminary promising data a post-hoc analysis of secondary assessment and endpoints was performed to evaluate potential effects of Sprifermin on semi-quantitatively evaluated structural MRI parameters. Aim of the present analysis was to determine effects of sprifermin on several knee joint tissues over a 12 month period. Methods: 1.5 T or 3 T MRIs were acquired at baseline and 12 months follow-up using a standard protocol. MRIs were read according to the Whole-Organ Magnetic Resonance Imaging Score (WORMS) scoring system (in 14 articular subregions) by four muskuloskeletal radiologists independently. Analyses focused on semiquantitative changes in the 100 μg subgroup and matching placebo of multiple MRI-defined structural alterations. Analyses included a delta-subregional and delta-sum approach for the whole knee and the medial and lateral tibio-femoral (MTFJ, LTFJ), and patello-femoral (PFJ) compartments, taking into account number of subregions showing no change, improvement or worsening and changes in the sum of subregional scores. Mann-Whitney − Wilcoxon tests assessed differences between groups. Results: Fifty-seven and 18 patients were included in the treatment and matched placebo subgroups. Less worsening of cartilage damage was observed from baseline to 12 months in the PFJ (0.02, 95 % confidence interval (CI) (−0.04, 0.08) vs. placebo 0.22, 95 % CI (−0.05, 0.49), p = 0.046). For bone marrow lesions (BMLs), more improvement was observed from 6 to 12 months for whole knee analyses (−0.14, 95 % CI (−0.48, 0.19) vs. placebo 0.44, 95 % CI (−0.15, 1.04), p = 0.042) although no significant effects were seen from the baseline visit, or in Hoffa-synovitis, effusion-synovitis, menisci and osteophytes. Conclusions: In this post-hoc analysis cartilage showed less worsening from baseline to 12 months in the PFJ, and BMLs showed more improvement from 6 to 12 months for the whole knee. Trial registration: ClinicalTrials.gov identifier: NCT01033994 .

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Bone marrow lesions, Cartilage, Magnetic resonance imaging, Osteoarthritis, Sprifermin
in
BMC Musculoskeletal Disorders
volume
17
issue
1
pages
7 pages
publisher
BioMed Central
external identifiers
  • scopus:84992034650
  • wos:000379711200001
ISSN
1471-2474
DOI
10.1186/s12891-016-1128-2
language
English
LU publication?
yes
id
ff932e81-8f13-4952-81a5-af8e00fbf554
date added to LUP
2016-11-08 14:17:37
date last changed
2017-01-01 08:38:59
@article{ff932e81-8f13-4952-81a5-af8e00fbf554,
  abstract     = {<p>Background: A recent publication on efficacy of Sprifermin for knee osteoarthritis (OA) using quantitatively MRI-defined central medial tibio-femoral compartment cartilage thickness as the structural primary endpoint reported no statistically significant dose response. However, Sprifermin was associated with statistically significant, dose-dependent reductions in loss of total and lateral tibio-femoral cartilage thickness. Based on these preliminary promising data a post-hoc analysis of secondary assessment and endpoints was performed to evaluate potential effects of Sprifermin on semi-quantitatively evaluated structural MRI parameters. Aim of the present analysis was to determine effects of sprifermin on several knee joint tissues over a 12 month period. Methods: 1.5 T or 3 T MRIs were acquired at baseline and 12 months follow-up using a standard protocol. MRIs were read according to the Whole-Organ Magnetic Resonance Imaging Score (WORMS) scoring system (in 14 articular subregions) by four muskuloskeletal radiologists independently. Analyses focused on semiquantitative changes in the 100 μg subgroup and matching placebo of multiple MRI-defined structural alterations. Analyses included a delta-subregional and delta-sum approach for the whole knee and the medial and lateral tibio-femoral (MTFJ, LTFJ), and patello-femoral (PFJ) compartments, taking into account number of subregions showing no change, improvement or worsening and changes in the sum of subregional scores. Mann-Whitney − Wilcoxon tests assessed differences between groups. Results: Fifty-seven and 18 patients were included in the treatment and matched placebo subgroups. Less worsening of cartilage damage was observed from baseline to 12 months in the PFJ (0.02, 95 % confidence interval (CI) (−0.04, 0.08) vs. placebo 0.22, 95 % CI (−0.05, 0.49), p = 0.046). For bone marrow lesions (BMLs), more improvement was observed from 6 to 12 months for whole knee analyses (−0.14, 95 % CI (−0.48, 0.19) vs. placebo 0.44, 95 % CI (−0.15, 1.04), p = 0.042) although no significant effects were seen from the baseline visit, or in Hoffa-synovitis, effusion-synovitis, menisci and osteophytes. Conclusions: In this post-hoc analysis cartilage showed less worsening from baseline to 12 months in the PFJ, and BMLs showed more improvement from 6 to 12 months for the whole knee. Trial registration: ClinicalTrials.gov identifier: NCT01033994 .</p>},
  author       = {Roemer, Frank W. and Aydemir, Aida and Lohmander, Stefan and Crema, Michel D. and Marra, Monica Dias and Muurahainen, Norma and Felson, David T. and Eckstein, Felix and Guermazi, Ali},
  issn         = {1471-2474},
  keyword      = {Bone marrow lesions,Cartilage,Magnetic resonance imaging,Osteoarthritis,Sprifermin},
  language     = {eng},
  number       = {1},
  pages        = {1--7},
  publisher    = {BioMed Central},
  series       = {BMC Musculoskeletal Disorders},
  title        = {Structural effects of sprifermin in knee osteoarthritis : a post-hoc analysis on cartilage and non-cartilaginous tissue alterations in a randomized controlled trial},
  url          = {http://dx.doi.org/10.1186/s12891-016-1128-2},
  volume       = {17},
  year         = {2016},
}