Five-year outcome of characterized chondrocyte implantation versus microfracture for symptomatic cartilage defects of the knee: early treatment matters

Background: Characterized chondrocyte implantation (CCI) results in significantly better early structural tissue regeneration than microfracture (MF), and CCI has a midterm clinical benefit over microfracture. Purpose: This study was undertaken to evaluate the 5-year clinical outcome of CCI in a randomized comparison with MF for the treatment of symptomatic cartilage defects of the femoral condyles of the knee. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Participants aged 18 to 50 years with a symptomatic isolated International Cartilage Repair Society (ICRS) grade III or IV cartilage lesion of the femoral condyles between 1 and 5 cm(2) were randomized to either CCI or MF. Clinical outcomes were measured up to 60 months after surgery using the Knee Injury and Osteoarthritis Outcome Score (KOOS). The main outcome parameter was change from baseline in overall KOOS (oKOOS). Adverse events were monitored. Results: Fifty-one participants were treated with CCI and 61 with MF. On average, clinical benefit was maintained through the 60-month follow-up period. The average change from baseline in oKOOS was not different between both groups (least squares [LS] mean +/- standard error [SE] 18.84 +/- 3.58 for CCI vs 13.21 +/- 5.63 for MF; P = .116). Treatment failures were comparable (n = 7 in CCI vs n = 10 in MF), although MF failures tended to occur earlier. Subgroup analysis revealed that CCI resulted in better outcome in participants with time since symptom onset of less than 3 years, which was statistically significant and clinically relevant (change in oKOOS 3 years mean +/- SE 13.09 +/- 4.78 for CCI vs 17.02 +/- 4.50 for MF, P = .554). Other subgroup analyses such as age (cutoff 35 years) did not show a difference. Female patients showed more failures irrespective of treatment. Conclusion: At 5 years after treatment, clinical outcomes for CCI and MF were comparable. In the early treatment group, CCI obtained statistically significant and clinically relevant better results than MF. Delayed treatment resulted in less predictable outcomes for CCI. These results provide strong evidence that time since onset of symptoms is an essential variable that should be taken into account in future treatment algorithms for cartilage repair of the knee