Laird Harrison

March 25, 2015

LAS VEGAS — Patients undergoing knee cartilage repair fare slightly better if the procedure includes autologous chondrocyte implantation, according to results from the ACTIVE trial.

For the implantation, physicians remove some of the patient's chondrocytes, culture them, and then implant them back into the patient.

"At 5 years, we saw them moving ahead," said James Richardson, MD, from the Orthopaedic Hospital NHS Foundation Trust in Shropshire, United Kingdom.

"This is a better cell than a stem cell," he told Medscape Medical News. "A chondrocyte is already determined to make cartilage."

Previous clinical trials of chondrocyte implantation have shown some success, but Dr Richardson and his team wanted to test the procedure in a large randomized clinical trial that reflects the "real-world" variety of patients who might benefit from it.

He presented the study results here at the American Academy of Orthopaedic Surgeons 2015 Annual Meeting.

The ACTIVE Trial

The team recruited 390 patients from Norway and the United Kingdom who had previously undergone unsuccessful repair of the articular cartilage in their knees. "These are difficult patients," said Dr Richardson.

Patients were randomly assigned to autologous chondrocyte implantation or to standard procedures, and an algorithm was used to ensure that the groups were balanced in number, age, size of defect, and preoperative Lysholm Knee Scoring Scale.

The mean size of the defects was 3.2 cm, and 88% of them were on a femoral condyle; 64% of the patients were men.

All the patients underwent surgery. The procedures, which varied depending on the recommendations of the surgeons, included debridement, abrasion, drilling, microfracture, mosaicplasty, and bone graft.

The difference between the two groups in time to failure — the primary end point of the study — was not significant. However, many patients who proceeded to further surgery did not return for an assessment by a physical therapist, making it difficult to measure failure rates, the investigators report.

Although patients improved on some measures of knee function, significant differences between the two groups did not emerge until year 5. By then, differences in Lysholm Knee Scoring Scale scores favored implantation (P = .11), as did differences in Cincinnati Knee Rating System scores, International Knee Documentation Committee scores (P = .02), EQ5D scores (P = .1), and satisfaction scores (P = .02).

Dr Richardson said he expects the differences to widen as cartilage continues to grow in the knees of the patients implanted with chondrocytes. The study is funded for another 5 years, he reported.

Right now, if I were a payer, you would be hard pressed to get me to pay for these things.

But these data are not enough to justify the additional expense of chondrocyte implantation, according to Joseph Bosco, MD, from the NYU Langone Medical Center in New York City.

Even the improvements that are statistically significant are not clinically significant, he told Medscape Medical News.

"Theoretically, if the data start to improve at 10 years and what they grow in the knee is superior to chondroplasty, maybe that's something that's hopeful," he said. "But right now, if I were a payer, you would be hard pressed to get me to pay for these things.

In the United States, he estimated, the cost of autologous chondrocyte implantation is around $40,000.

There could be subgroups of patients, such as those with lesions larger than 2 cm, who could benefit from autologous chondrocyte implantation.

However, the variety of treatments used could complicate interpretation of the results, said David Ricker, MD, chief medical officer of Vericel, a cellular therapy company in Cambridge, Massachusetts.

The patients knew whether or not they were being treated with autologous chondrocyte implantation, so a placebo effect could not be eliminated, Dr Ricker told Medscape Medical News.

This study was funded by the UK Medical Research Council. Dr Bosco has disclosed no relevant financial relationships. Dr Ricker is an employee of Vericel.

American Academy of Orthopaedic Surgeons (AAOS) 2015 Annual Meeting: Abstract P409. Presented March 24, 2015.


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