FDA reports on chondrocyte implant’s adverse events

Graft failure, delamination and tissue hypertrophy the most commonly reported complications for Genzyme’s Carticel implant.

Researchers with the FDA found that 497 adverse events were reported to the FDA’s MedWatch system for 294 patients treated with Genzyme’s Carticel autologous chondrocyte implant from 1996 to 2003.

The FDA approved Carticel in 1997 for repairing symptomatic cartilaginous defects of the femoral condyle in patients with a poor response to arthroscopy or surgical repair, and Genzyme’s 2002 annual report indicated that Carticel was used in at least 7500 patients since 1995. Using that information, the FDA estimated a 3.8% adverse event-reporting rate, according to the study.

While only manufacturers must report all serious adverse events within 15 days, reporting is voluntary for clinicians and others, the study authors noted. “Therefore, the number of reports of adverse events is likely to underestimate the actual number of occurrences,” they said.

The report noted the most common adverse events included graft failure (25%), delamination (22%) and tissue hypertrophy (18%). Eighteen infections were also reported.

“As is the case with any therapy, the anticipated benefits of autologous chondrocyte implantation must be weighed against the potential risks,” the authors said.

An FDA spokesperson told Orthopedics Today that the FDA continues to monitor the reports on Carticel’s safety through post-market surveillance and through the MedWatch system in particular. He noted that these adverse event reports are not unique to Carticel and are “relatively common.”

“Carticel is the first [FDA]-licensed somatic cellular therapy; thus, it is especially important to monitor its safety and to communicate the surveillance data to the medical community,” the study authors noted.

Multiple adverse events in 46%

Jennifer J. Wood, PhD, MPH, and colleagues at the FDA’s center for Biologics Evaluations and Research in Rockville, Md., conducted the study. They found that among the 294 patients with reported adverse events, 135 (46%) reports were for more than one event. Overall, patients with reported adverse events had a mean age of 38 years, with 63% in men and 37% in women.

The median time between Carticel implantation and adverse event diagnosis was 240 days, ranging from one day to 2105 days. The anatomic site, noted in 270 reports, included 258 (96%) in the femoral condyles and 12 (4%) in other knee sites, according to the study.

The study also found five reports of deep vein thrombosis and two reports of pulmonary embolism. However, “both ... are known potential complications of knee surgery,” the authors said.

FDA researchers also found 18 surgical site infections, including 11 joint infections and seven superficial wound infections, which occurred a mean 14 days postop. Four of the 11 joint infections were caused by Staphylococcus species, two were from gram-positive rods, one from Enterobacter cloacae and one was a herpes joint infection, according to the study.

Revisions after implantation

After Carticel implantation, 93% of the patients with reported adverse events underwent 389 surgical revisions. These included 187 (48.1%) cartilage procedures to treat problems directly related to the graft, such as chondroplasty, debridement and microfracture. Another 97 (24.9%) revisions involved periarticular soft-tissue procedures. Additionally, surgeons performed 63 (16.2%) reoperations to correct intra-articular problems, 29 (7.45%) reoperations for resurfacing or realignment — including eight total knee replacements — and 13 (3.3%) reoperations to cleanse the joint.

However, the authors noted: “The nature of our data ... does not permit a direct comparison of infection rates; the infection rate among persons receiving Carticel may be higher than, equal to, or lower than that among similar patients managed with alternative operative procedures.”

For more information:
Wood J, Malek M, Frassica F, et al. Autologous cultured chondrocytes: Adverse events reported to the United States Food and Drug Administration. J Bone Joint Surg. 2006;88-A:503-507.