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

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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; Crema, Michel D.; Marra, Monica Dias; Muurahainen, Norma; Felson, David T.; Eckstein, Felix; Guermazi, Ali.

I: BMC Musculoskeletal Disorders, Vol. 17, Nr. 1, 2016, s. 1-7.

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Roemer, Frank W. ; Aydemir, Aida ; Lohmander, Stefan ; Crema, Michel D. ; Marra, Monica Dias ; Muurahainen, Norma ; Felson, David T. ; Eckstein, Felix ; Guermazi, Ali. / Structural effects of sprifermin in knee osteoarthritis : a post-hoc analysis on cartilage and non-cartilaginous tissue alterations in a randomized controlled trial. I: BMC Musculoskeletal Disorders. 2016 ; Vol. 17, Nr. 1. s. 1-7.

RIS

TY - JOUR

T1 - Structural effects of sprifermin in knee osteoarthritis

T2 - a post-hoc analysis on cartilage and non-cartilaginous tissue alterations in a randomized controlled trial

AU - Roemer, Frank W.

AU - Aydemir, Aida

AU - Lohmander, Stefan

AU - Crema, Michel D.

AU - Marra, Monica Dias

AU - Muurahainen, Norma

AU - Felson, David T.

AU - Eckstein, Felix

AU - Guermazi, Ali

PY - 2016

Y1 - 2016

N2 - 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 .

AB - 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 .

KW - Bone marrow lesions

KW - Cartilage

KW - Magnetic resonance imaging

KW - Osteoarthritis

KW - Sprifermin

UR - http://www.scopus.com/inward/record.url?scp=84992034650&partnerID=8YFLogxK

U2 - 10.1186/s12891-016-1128-2

DO - 10.1186/s12891-016-1128-2

M3 - Article

VL - 17

SP - 1

EP - 7

JO - BMC Musculoskeletal Disorders

JF - BMC Musculoskeletal Disorders

SN - 1471-2474

IS - 1

ER -