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

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.

Fig. 1

Sagittal intermediate-weighted fat suppressed MRI in treated patient at baseline (a), 3 months (b) and 6 months (c) follow up show improvement of cartilage focal defect of the posterior medial femoral condyle with almost perfect filling at 6 months (long arrows). Also note the grade 1 BML at the central weight-bearing medial femoral condyle disappears at 3 months (a, short arrows). There is a Hoffa-synovitis grade 1 and moderate size tibial osteophytes. There is a femoral intrachondral osteophyte that seems to be slightly increasing in size (dotted arrows)

Fig. 2

Axial intermediate-weighted fat-suppressed MRI in treated patient at baseline (a) and 12 months (b) follow up show improvement of cartilage focal defect and thickness of the medial patella (long arrows). Also note the decrease in volume of the joint effusion (small arrows)

Fig. 3

Coronal intermediate-weighted fat-suppressed MRI in treated patient at baseline (a) and 3 months (b) follow up show no improvement of cartilage damage in the medial tibiofemoral compartment (WORMS grade 6 at central medial femur; WORMS grade 5 at central medial tibia). There is a medial meniscal maceration/extrusion (arrow). There is a slight improvement of the subchondral bone marrow lesion/cysts at the central medial tibia (small arrows) and slight worsening of the subchondral bone marrow lesion/cysts at the central medial femur (long arrows). Note large medial osteophytes