(From Genzyme Website 9/02)
CLINICAL EXPERIENCE
Clinical information regarding the use of
autologous cultured chondrocytes is available from 2 sources: 1) a series
of patients treated in Sweden, and 2) a U.S. patient registry. Patients in
the Swedish series received an autologous cultured chondrocyte product
which was produced slightly differently than Carticel®, the
U.S. product.
The series consists of 153 consecutive patients who received autologous cultured chondrocyte implantations for various defects of the knee. Clinical follow-up ranged from 1 week to 94 months. Most patients had arthroscopic evaluation; a subset had biopsy and histological evaluations. Patients presented with cartilaginous defects of the femoral condyle, patella, tibia, a combination of these, or osteochondritis dissecans, with or without non-cartilaginous defects such as anterior cruciate ligament damage requiring repair.
Following autologous cultured chondrocyte implantation, patients were routinely followed for various durations. All patients were retrospectively classified as having one of the three clinical outcomes: resumed all activities, some improvement, or no improvement. Clinical outcomes were also reported for patient subgroups including: 1) those with femoral condyle lesions who had at least 18 months of follow-up, and 2) those who failed an earlier procedure. Most patients were also assessed for arthroscopic outcomes and some patients were assessed for histological outcomes.
Clinical Outcome - Patients with Femoral Condyle
Lesions
A total of 78 of 153 patients in the Swedish
series had femoral condyle lesions with or without concurrent
non-cartilaginous knee lesions. Patients had one or more defects ranging
in size from <1-20 cm2. Approximately 90% of the patients
had defects of <10 cm2. Clinical outcomes are shown below
for 40 patients who received autologous cultured chondrocytes and were
evaluable after at least 18 months of follow-up (median = 25; range =
18-94 months). In this evaluation, 70% of the patients demonstrated some
clinical benefit when compared to their pre-operative condition.
Patient Response to Treatment
| Defect | Resumed all activities |
Some improvement |
No improvement |
Total |
| Femoral Condyle | 7 (29%) | 8 (33%) | 9 (38%) | 24 |
| Femoral Condyle plus other Non-Cartilage Repair |
4 (25%) | 9 (56%) | 3 (19%) | 16 |
| Total | 11 (28%) | 17 (42%) | 12 (30%) | 40 |
No apparent association of clinical outcomes with lesion size or cell dose could be demonstrated.
Clinical Outcome - Patients With Osteochondritis
Dissecans Lesions
Clinical outcomes are shown below for 12
patients who received autologous cultured chondrocytes and were evaluable
after at least 18 months of follow-up (median = 25; range = 18-94 months).
In this evaluation, 83% of the patients demonstrated some clinical benefit
when compared to their pre-operative condition.
Patient Response to Treatment
| Defect | Resumed all activities |
Some improvement |
No improvement |
Total |
| Osteochondritis Dissecans | 6 (50%) | 4 (33%) | 2 (17%) | 12 |
Clinical Outcome - Failed Earlier Procedures
Debridement of the cartilage defect is often
performed along with Carticel® (autologous cultured
chondrocytes) administration. 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 greater than the time period to failure
of their initial debridement. These patients had a range of cartilage
defects. At the end of follow-up, 5 (23%) patients had a functional
outcome rating of "resumed all activities," 8 (36%) patients had
a rating of "some improvement," and 9 (41%) patients had a
rating of "no improvement." Thus, 13/22 (59%) patients who had
failed an earlier debridement had outcomes following autologous cultured
chondrocyte implantation which were more favorable and durable than those
following their earlier therapy.
Histological Outcome
Twenty-two of the initial 23 patients in the Swedish series had
histological evaluation of biopsies from the transplant site. Fifteen of
those patients had defects of the femoral condyle and 7 had defects of the
patella. Six of the 15 femoral condyle patients showed only hyaline
cartilage on their biopsy, 5 had a mixture of hyaline and fibrocartilage,
and 4 had only fibrocartilage. Of the 6 patients with only hyaline
cartilage on biopsy, 2 had minimal to no defects and 4 had more extensive
defects (e.g., fissures, fibrillations, etc.).
Arthroscopic Outcome
Most of the 153 patients had arthroscopy. The quality of repair observed
at arthroscopy correlated with the clinical outcomes. A substantial number
of patients were noted at arthroscopy to have tissue hypertrophy (see
Adverse Events).
Data from the US registry included 38 patients with femoral condyle lesions who received the Carticel®(autologous cultured chondrocytes) product and had at least 12 months of follow-up. Only functional outcome data were collected; no arthroscopic or histologic data are available. 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.
Two post-marketing studies are under way to evaluate the long term durability of the Carticel®repair in patients who have failed a prior surgical repair procedure. Prior surgical repair procedures are surgical interventions intended to correct cartilaginous defects such as marrow stimulation techniques, transplantation of cells or tissues, or debridement followed by an adequate rehabilitation program. Repair procedures, however, do not include lavage, biopsy, or diagnostic arthroscopy.
Updated 9/27/02
| Patient Registry (Older Info) | |
SUMMARY
Cartilage Repair Registry, Volume 4 - February 1998
Indication
- Carticel™ (autologous cultured chondrocytes) (AuCC) is approved by the FDA as a biologic for the repair of clinically significant, symptomatic defects of the femoral condyle (medial, lateral or trochlea) caused by acute or repetitive trauma.
- Carticel is not recommended for patients with osteoarthritis.
- For a complete discussion of indications, warnings, precautions and adverse events please refer to accompanying package insert.
- Landmark event for Carticel, Volume 4 data includes two year patient outcomes for patients treated outside of Sweden.
- International, multicenter experience from 410 sites; 307 (U. S.) and 103 (Europe).
Patient Participation:- 273 with 12-month follow-up
- 50 with 24-month follow-up
- Progressive, statistically significant improvement in patient overall condition and symptomatology demonstrated at both 12 and 24 months, when compared to baseline condition.
- Data registry continues to confirm positive outcomes achieved in Sweden with AuCC.
Population
- 97% between 15 and 55 years (average 35 years)
- 74% had previous surgery, 62% to treat articular injuries in the past five years
- 91% of the lesions on the distal femur
- 4.4 cm2 average size defect, after debridement; 79% > 2 cm2
Clinician & Patient Evaluation Overall Condition 24-Month
Compared to Baseline 
Note: Based upon a modified Cincinnati Knee Rating System. Treatment failures were assigned a "2" for follow-up
Clinician & Patient Evaluation Overall Condition 24-Month Compared to Baseline:
| CLINICIAN EVALUATION | |||||
| n | Improve % | Same % | Decline % | Mean Change | |
| MFC | 25 | 80% | 16% | 4% | (+) 3.80 |
| LFC | 5 | 100% | 0% | 0% | (+) 5.20 |
| Trochlea | 4 | 100% | 0% | 0% | (+) 3.25 |
| Femur | 43 | 86% | 12% | 2% | (+) 4.14 |
| Overall | 50 | 78% | 16% | 6% | (+) 3.64 |
| PATIENT EVALUATION | |||||
| n | Improve % | Same % | Decline % | Mean Change | |
| MFC | 25 | 72% | 8% | 20% | (+) 2.76 |
| LFC | 4 | 100% | 0% | 0% | (+) 5.50 |
| Trochlea | 4 | 75% | 25% | 0% | (+) 2.50 |
| Femur | 42 | 79% | 7% | 14% | (+) 3.43 |
| Overall | 49 | 74% | 10% | 16% | (+) 3.02 |
Knee Examination:
- 24 Month Results Compared to Baseline: Significant declines are evident from baseline.
*Note: Treatment failures were considered to have symptoms present at
follow-up.
Patient Reported Symptomatology:
- 24 Month Results Compared to Baseline: Significant reduction in symptoms of pain and swelling at both 12 and 24 months post implantation.
*Note: Based on modified Cincinnati Knee Rating System
Treatment failures were assigned a "2" for follow-up
Safety Profile
- 87% (n=779) of patients reported no adverse events or complications following implantation.
- 5% had a complication considered to be at least possibly related to the AuCC.
- Adhesions / fibroarthrosis (3%) and hypertrophic changes (2%) were the most frequent complication of the knees treated.
- Cumulative incidence of treatment failure is 3.3% at 12 months and 5.8% at 24 months following implantation.
Re-operation Rate
- 90% of patients treated did not report a re-operation to the registry.
- Majority of re-operations were performed arthroscopically. Shaving, trimming or debridement (6.5%) and manipulation / lysis of adhesions (2.4%) being the most prevalent.
- 4.8% had a re-operation considered to be at least possibly related to the implantation.
- AuCC at both 12 and 24 month intervals, continues to appear safe and effective.
- Improvement seen at 12 months for overall knee condition, patient symptomatology and knee examination results remain durable at 24 months.
- 86% of femoral condyle patients improve from baseline, as rated by their clinicians.
- 79% of femoral condyle patients rate themselves as improved from baseline.
- 87% of patients reported no adverse events.
- 90% of patients reported no re-operation.
- Incidence of failure is 3.3% and 12 months and 5.8% at 24 months.
Recommendations
- Treating surgeons should closely adhere to the product labeling.
- Procedure should not be used in patients with osteoarthritis, instability or abnormal loading or tracking of the knee.
- Participation and commitment to the Registry be maintained.
- Comprehensive data collection should become the standard for all evaluations of articular cartilage defects.
Data management and statistical analysis performed by Abt Associates Inc. Results reviewed by Orthopedic Registry Advisory Board.