Structural effects of intra-articular TGF-β1 in moderate to advanced knee osteoarthritis: MRI-based assessment in a randomized controlled trial

BMC Musculoskelet Disord. 2017 Nov 16;18(1):461. doi: 10.1186/s12891-017-1830-8.

Abstract

Background: To determine effects of allogeneic human chondrocytes expressing TGF-β1 (TG-C) on structural progression of MRI features of knee osteoarthritis over a 1 year period.

Methods: This phase II randomized controlled trial of TG-C included patients with moderate to advanced osteoarthritis. Patients were randomized to receive an intraarticular 3:1 mixture of non-transduced allogeneic human chondrocytes and TG-C or placebo. 3 T MRI was acquired for all patients at baseline and follow-up (3, 6 and 12 months). MRIs were assessed using the WORMS system including cartilage damage, bone marrow lesions (BMLs), meniscal damage/extrusion, Hoffa-, effusion-synovitis, and osteophytes. Analyses were performed on a whole knee level, compartmental level, and subregional level. Binary logistic regression with Generalized Estimating Equation was used to compare risks of progression, adjusting for baseline age and gender. Mann - Whitney - Wilcoxon tests were used to assess differences for continuous variables.

Results: Fifty-seven Patients were included in the TG-C group and 29 in the placebo group. At 12 months, knees in the TG-C group showed less progression of cartilage damage compared to placebo on a whole knee level (34.6% vs. 47.9%; adjusted RR 0.7, 95%CI [0.5-1.1], p = 0.077). Less progression of Hoffa-synovitis and effusion-synovitis was observed in the TG-C group compared to placebo (9.6% vs. 21.1%, adjusted RR 0.5, 95%CI [0.2,1.2], p = 0.115). No statistically significant differences were seen for BMLs, meniscal damage and osteophytes.

Conclusions: Intraarticular treatment with TG-C showed fewer patients in the treated group with progression in structural OA features and other MRI-defined inflammatory markers such as Hoffa-synovitis and effusion-synovitis. However, no differences were observed in regard to progression of BMLs and meniscal damage, or hypertrophic osteophyte formation.

Trial registration: NCT01221441 .Registered 13th October, 2010.

Keywords: MRI; Osteoarthritis; Randomized controlled trial; Tgf-β1.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Cartilage, Articular / cytology
  • Cartilage, Articular / diagnostic imaging
  • Cartilage, Articular / pathology*
  • Cell- and Tissue-Based Therapy / methods
  • Chondrocytes / metabolism
  • Chondrocytes / transplantation*
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Injections, Intra-Articular
  • Knee Joint / diagnostic imaging
  • Knee Joint / pathology*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Osteoarthritis, Knee / diagnosis
  • Osteoarthritis, Knee / pathology
  • Osteoarthritis, Knee / therapy*
  • Osteophyte / diagnostic imaging
  • Osteophyte / pathology
  • Osteophyte / therapy
  • Placebos
  • Severity of Illness Index
  • Transduction, Genetic
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism*
  • Transplantation, Homologous

Substances

  • Placebos
  • TGFB1 protein, human
  • Transforming Growth Factor beta1

Associated data

  • ClinicalTrials.gov/NCT01221441