PROBLEMS AND ISSUES
About 200,000 total knee replacement operations are performed annually at a cost of $25,000 each. The artificial joint generally lasts only 10-15 years and is considered a poor treatment option for people under the age of 50. If treatment or cartilage injuries of the knee occurs at an early stage, it could prevent the development of osteochondritis, and so the need for a total joint replacement might be delayed or eliminated. In the knee, full-thickness defects of cartilage have a poor capacity for repair. Damage to cartilage causes pain and difficulty in moving the joint. Unlike other body tissue, cartilage is avascular (without its own blood supply) and cannot repair itself. Osteoarthritis may result and therefore require total knee replacement. Total knee replacement is most commonly performed in people over 60 years of age. The treatment of younger patients (under 50) is more troublesome, because the prostheses have a limited lifetime. Autologous chondrocyte transplantation was performed on patients aged 14-55. The patients were followed for 16-66 months (mean 39). It was discovered that cultured autologous chondrocytes can be used to repair deep cartilage defects in the femorotibial articular surface of the knee joint. All patients in the study had a considerable decrease in knee pain, swelling, and crepitation, and knee locking completely disappeared.
The new treatment is used in people with cartilage damage to the part of the knee formed by the end of the thigh bone. Patients with this type of damage generally display symptoms that include locking, catching, localized pain, and swelling. The results indicate that cultured autologous chondrocytes can be used to repair articular cartilage defects in the femorotibial joint, and show that this treatment restores the function of the joint by forming predominantly hyaline-like cartilage containing type II collagen. However, the mechanism of the repair process is unknown.
The procedure enables patients to grow new hyaline cartilage in their knees. Hyaline cartilage is the tough, slippery tissue that cushions the ends of bones where they form a joint. It lets bones glide smoothly during joint motion, and distributes the force evenly during running, jumping, and other repetitive movements. Hyaline cartilage consists of chondrocytes and extracellular matrix. The matrix contains a variety of macromolecules, including type II collagen and proteoglycan. The structure of the matrix allows the cartilage to absorb shock and withstand shearing and compression forces. After a surgical procedure is completed, fibrocartilage rather than hyaline cartilage is most commonly produced. Fibrocartilage has limited ability to withstand shock and shearing forces.
Orthopedic surgeons reported that 85% of patients treated with Genzyme Tissue Repair’s Carticel® (autologous cultured chondrocytes) to repair damaged cartilage on the thigh-bone part of the knee, showed improvement in four key measures three years after therapy. There is a growing consensus in the orthopedic community about the important role of Carticel® in treating patients.
The fifth registry report included data collected on 40 patients at the 36-month follow-up visit, 220 patients at the 24-month follow-up visit, and 588 patients after 12 months, over four key measures: clinician and patient evaluations of overall knee condition, patient reports of symptoms, such as pain and swelling, and knee examination results.
Carticel® surgery is not yet approved for people with osteo or rheumatoid arthritis. Currently, the procedure is limited to patients aged 55 or younger. Carticel® was licensed by the FDA in August 1997 for the repair of defects on the femoral condyle, or thigh-bone part of the knee.
Since the FDA approved the use of Carticel®, the number of patients covered by insurance plans has greatly increased. A recent study found that 50% of large orthopedic groups in the metropolitan areas of: Chicago, Boston, Los Angeles, and San Francisco, were trained in the use of Carticel®. These markets represent 39 million people or 15% of the U.S. population. Health plans with protocols for Carticel® approve reimbursement whenever patients meet the criteria set out in the protocol.
Carticel® is not intended for use in patients who have an infection at any of the operative sites, osteoarthritis, or inflammatory diseases. It is also not recommended for use in patients with a known history of an allergy to materials of bovine origin or with an allergy to gentamycin. Instability of the knee or an abnormal distribution of weight within the joint may also adversely affect the success of the procedure and should be corrected prior to Carticel® implantation. Patients who have previously had cancer in the bones, cartilage, fat, or muscle of the treated limb should also not be treated with Carticel®.
Any potential intra-operative and postoperative complications associated with a knee arthrotomy may occur with autologous chondrocyte implantation as well. While there appear to be no particular adverse events directly related to implantation of autologous chondrocytes, risks from the surgical procedure, including infection and inflammatory response, should be taken into consideration. Possible adverse events associated with this therapy may include wound infection, arthralgia, arthrosis, arthropathy, implant complication and fever. The most frequent adverse events reported in the registry include adhesions and overgrown tissue at the cartilage repair site and loosening of the Carticel® graft.
Currently, Genzyme is focusing in the following areas to increase the acceptance of Carticel®: expanding studies to document the safety and effectiveness of the new treatment and educating third-party payers to increase the number providing reimbursement for the treatment. The use of Carticel® depends on its market acceptance, levels of reimbursement approvals, and the competitive environment for treatments for cartilage damage.
At a meeting of the American Academy of Orthopedic Surgeons, caution and the need for more study and data on chondrocyte transplantation was urged. Some surgeons felt that the procedure has been market driven by the public, which has unrealistic expectations of outcomes. The physicians have a desire to educate themselves, and want to determine what scientific information they need before the procedure is taken to widespread application. The long-term effect of cartilage harvesting on knee function and the long term safety of cartilage implantation are unknown. Multicenter trials are recommended. Currently, many orthopedic surgeons look at the procedure positively, but with skepticism and caution, as more data on autologous chondrocyte transplantation is needed to determine whether to advise patients to undergo the procedure. There are many reports in literature, which describe operations that look good for the first one to five years, but results beyond that are difficult to confirm. In addition, a control group would be useful to further validate reports so far. It is important to obtain more scientific data, rather than reports that some patients are happy. Some of these questions will be resolved by the clinical trials in progress.
Introduction How it Works Cost and Statistics Data and Results Looking Toward the Future