Clinical information regarding the use of autologous cultured chondrocytes was obtained from 2 open-label, observational studies consisting of a series of patients treated in Sweden and the Cartilage Repair Registry. Patients in the Swedish series received an autologous cultured chondrocyte product similar to Carticel®.

14.1.1 Swedish Series

The series consists of 153 patients who received autologous chondrocyte implantation for various defects of the knee. Patients presented with cartilage defects of the femoral condyle, patella, tibia, a combination of these, or osteochondritis dissecans, with or without comorbidity such as anterior cruciate ligament insufficiency requiring reconstruction.

Following autologous chondrocyte implantation, patients were followed for various durations. Clinical follow-up ranged from 1 week to 94 months; 86 patients had at least 18 months of follow-up. Most patients had arthroscopic evaluation; a subset had biopsy and histological evaluations. All patients were retrospectively classified as having one of three clinical outcomes: resumed all activities, some improvement, or no improvement. Clinical outcomes were also reported for patient subgroups including: 1) 40 patients with femoral condyle lesions, 2) 12 patients with osteochondritis dissecans lesions and 3) 22 patients who failed a prior debridement. 

1) Clinical Outcome - Patients with Femoral Condyle Lesions

A total of 78 of 153 patients had femoral condyle lesions with or without co-morbidity. Patients had one or more defects ranging in size from < 1-20 cm2. Of the patients with femoral condyle lesions, 40 were evaluable after at least 18 months (median = 25; range = 18 to 94 months). Clinical outcomes for the 40 patients are summarized in Table 5.

2) Clinical Outcome – Patients with Osteochondritis Dissecans Lesions

Of the 12 patients who received autologous cultured chondrocytes for treatment of an osteochondritis lesion, 6 of the 12 had "resumed all activities", 4 had "some improvement" and 2 had "no improvement" after the 18-month (median = 25; range = 18-94 months) follow-up period.

3) Clinical Outcome – Failed Earlier Procedures

Debridement of the cartilage defect is often performed along with administration of autologous cultured chondrocytes. To help differentiate the effects of the autologous cultured chondrocyte implantation procedure from those of debridement alone, an analysis was performed on 22 patients who had failed prior debridement and had a follow-up period after autologous cultured chondrocyte implantation which was at least as long as the time period to failure of their initial debridement. At the end of follow-up, 5 of the 22 patients had a functional outcome rating of "resumed all activities", 8 of the 22 patients had a rating of "some improvement" and 9 of the 22 patients had a rating of "no improvement." Thus, 13 of the 22 patients (59%) who had failed an earlier debridement had outcomes that were more favorable and durable following autologous cultured chondrocyte implantation than their previous debridement without cells.

Histological Outcome

Twenty-two (22) patients in the Swedish series had histological evaluation of biopsies from the implant site one or more years after their autologous chondrocyte implantation. Fifteen (15) of those patients had defects of the femoral condyle and 7 had defects of the patella. Six (6) of the 15 femoral condyle biopsies showed hyaline-like cartilage, 5 had a mixture of hyaline and fibrocartilage, and 4 had only fibrocartilage. Of the 6 biopsies with hyaline-like cartilage, 2 had minimal to no surface irregularities and 4 had some surface irregularities (e.g., fissures, fibrillations, etc.).

Arthroscopic Outcome

As an objective outcome evaluation, 86 of the 153 patients had a follow-up arthroscopy for investigational purposes at 18 months or more post-implantation. In some cases, the quality of repair observed at arthroscopy was considered to be supportive of the clinical or functional outcomes. A substantial number of patients were noted at arthroscopy to have tissue hypertrophy [see Adverse Reactions (6)].

14.1.2 Cartilage Repair Registry

The Cartilage Repair Registry (CRR) was established upon the introduction of Carticel® into orthopedic practice in March of 1995. The CRR was designed to prospectively collect the clinical outcomes of Carticel and other cartilage repair treatments for chondral lesions in the knee. Clinical data were collected at baseline arthroscopy, implantation, intervals of 6 and 12 months, and annually thereafter; adverse reaction data were collected on an ongoing basis through CRR adverse reaction collection and spontaneous reporting. Inclusion in the CRR was based on a qualifying event that was defined as a knee arthroscopy in which a chondral lesion was identified and a cartilage biopsy was harvested. Participation in the CRR was voluntary, and not all patients biopsied or implanted were included. As of November 21, 1997, 891 patients had been implanted worldwide, and 644 of these patients were included in the CRR. Functional outcomes were based on responses to a modified version of the Cincinnati Knee Rating System.

Data from a subset of 191 US patients in the CRR as of December 31, 1996 who had undergone repair of lesions on the femoral condyle (medial, lateral or trochlea) were assessed to support licensure. Patients were between the ages of 15-57, 66% (126/191) were male, and 34% (64/191) were female and one patient's gender was not reported. Of these 191 patients, 38 had at least 12 months of follow-up. At study baseline, these 38 patients' mean rating of overall condition was 3.2, which is defined as fair to poor: limitations that affect activities of daily living-no sports possible. At 12 month follow-up, these patients reported an overall condition score of 6.4 defined as good: some limitation with sports but can participate if patient compensates. Although these patients were rated according to outcome measurements different from those used in the Swedish series, the results were consistent with the Swedish experience.