Abstract
Genetically engineered chondrocytes virally transduced with a transforming growth
factor (TGF)-β1 (TG-C [TissueGene-C]) expression vector have been shown to have potential benefits
in the nonoperative management of knee osteoarthritis. Previous literature has reported
on safe dosages of TG-C. Therefore, the purpose of this study was to evaluate the
Phase II results and a 24-month efficacy of this injectable mixture compared with
placebo in patients with Kellgren–Lawrence (K–L) grade III knee osteoarthritis. Specifically,
we assessed (1) functional outcomes, (2) pain scores, (3) adverse events (AEs), and
(4) magnetic resonance imaging (MRIs) findings. We performed a multicenter, double-blinded,
placebo-controlled, and randomized study of adults who had K–L grade III knee osteoarthritis.
A total of 102 patients were 2:1 randomized to TG-C at a dose of 3.0 × 107 cells, or placebo injections between May 1, 2011 and October 31, 2012. Outcomes analyzed
were knee joint function, pain, quality of life, adverse events, and MRI findings
using the whole-organ magnetic resonance imaging score (WORMS) system. There were
significant improvements in the International Knee Documentation Committee (IKDC)
and visual analogue scale (VAS) scores in the TG-C cohort, when compared with the
placebo cohort at weeks 12, 52, 72, and 104 (p < 0.05). No severe AEs were observed. Common AEs were arthralgia, joint inflammation,
and joint effusion which were similar between both cohorts. Whole-knee MRIs at 12
months showed less progression of cartilage damage, infrapatellar fat pad-synovitis,
and effusion-synovitis in the TG-C cohort. Patients who received TG-C had significant
improvements in IKDC and VAS scores. These patients also reported less severe and
frequent pain. Additionally, fewer patients treated with TG-C showed progression of
cartilage damage, as well as less progression of infrapatellar fat pad synovitis and
effusion-synovitis. Furthermore, treatment with TG-C was generally well tolerated
with minor AEs. Therefore, based on these results, TG-C appears to be a safe and effective
modality for the management of K–L grade III osteoarthritis.
Keywords
genetically modified - growth factors - knee - osteoarthritis - pain
