Surgery Section - Autologous Chondrocyte Implantation

IMPORTANT REMINDER

This Medical Policy has been developed through consideration of medical necessity, generally accepted standards of medical practice, and review of medical literature and government approval status.

Benefit determinations should be based in all cases on the applicable contract language. To the extent there are any conflicts between these guidelines and the contract language, the contract language will control.

The purpose of medical policy is to provide a guide to coverage. Medical Policy is not intended to dictate to providers how to practice medicine. Providers are expected to exercise their medical judgment in providing the most appropriate care.

DESCRIPTION

Damaged hyaline cartilage in joints (articular cartilage) typically fails to heal on its own.  It can be associated with pain, loss of function and disability, and may lead to debilitating osteoarthritis. Conventional treatment options include debridement to remove diseased membranes, bone or cartilage, and subchondral drilling, microfracture, and abrasion arthroplasty to induce the growth of fibrocartilage into the chondral defect.  This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage, and may deteriorate over time.

Autologous chondrocyte implantation (ACI) involves the placement of the patient’s own chondrocytes into the chondral defect.  ACI attempts to regenerate hyaline-like cartilage for patients with inadequate response to conventional treatment.

Only Carticel™ has received approval by the U.S. Food and Drug Administration (FDA) for the culturing of chondrocytes. The FDA approval document specifies the following restrictions:

• Carticel is indicated for the repair of symptomatic cartilaginous defects of the femoral condyle (medial, lateral or trochlear), caused by acute or repetitive trauma, in patients who have had an inadequate response to a prior arthroscopic or other surgical repair procedure.
• Carticel is not indicated for the treatment of cartilage damage associated with osteoarthritis.
• Carticel should only be used in conjunction with debridement, placement of a periosteal flap and rehabilitation.
• The independent contributions of the autologous cultured chondrocytes and other components of the therapy to outcome are unknown. Data regarding functional outcomes beyond three years of autologous cultured chondrocyte treatment are limited.
  

POLICY/CRITERIA

1. Autologous chondrocyte implantation may be considered medically necessary for the treatment of disabling full thickness articular cartilage defects of the knee caused by acute or repetitive trauma when all of the following criteria are met:
   1. Adolescent patients should be skeletally mature with documented closure of growth plates (e.g., 15 years or older). Adult patients should be too young to be considered an appropriate candidate for total knee arthroplasty or other reconstructive knee surgery (e.g., younger than 55 years)
   2. Focal, full thickness (grade III or IV) uni-polar lesions on the weight bearing surface of the femoral condyles or trochlea at least 1.5 cm² in size
   3. Inadequate response to a prior arthroscopic or other surgical repair procedure on the involved knee
   4. Documented minimal to absent degenerative changes in the surrounding articular cartilage (Outerbridge Grade II or less), and normal appearing hyaline cartilage surrounding the border of the defect
   5. Normal knee biomechanics, or alignment and stability achieved concurrently with autologous chondrocyte implantation
   6. Absence of meniscal pathology
   7. Body mass index (BMI) < 35
      
      
2. Autologous chondrocyte implantation for any indications other than listed above, including but not limited to first-line treatment and treatment of defects of the patella, talus and any joints other than the knee is considered investigational.

POSITION SUMMARY

Although the long-term safety and effectiveness is unknown, current data suggests that autologous chondrocyte implantation (ACI) of the knee may be an appropriate surgical option for carefully selected patients who would otherwise require total knee replacement.

The effectiveness and safety of ACI for the treatment of cartilage defects of joints other than the knee or as a first-line treatment of the knee have not been established.

Current data consists of short- to intermediate-term randomized, controlled clinical trials, unreliable retrospective reviews, registry data and case series.

There is a lack of general consensus in the surgical community on technique for performing ACI.

Effectiveness

Knee

Randomized, controlled trial (RCT) data currently consist of seven short- to intermediate-term trials.

• One RCT reported significantly greater improvement at one-year follow-up in the group of patients who received ACI (n=25) compared to the group who received microabrasion (n=25). (6)
• Three RCTs comparing ACI with microfracture in a total of 198 patients reported no significant difference at 18 months, two years and five years, respectively (7-9)
• In three RCTs with a total of 184 patients, more patients in the ACI group (98%) reported significant improvement than did patients in the osteochondral autograft group (69%).(10-12)
• The protocol for one of these studies demonstrated the reason ACI is not indicated as first-line treatment. (12) Patients were required to undergo arthroscopic debridement at least six months prior to either ACI or mosaicplasty. Debridement resulted in spontaneous improvement in 32% of these patients sufficient to eliminate the need for further surgery.

The results of the Study of the Treatment of Articular Repair (STAR) trial suggested ACI may improve knee symptoms and function in some patients with severe, debilitating, previously treated cartilage lesions of the distal femur for up to four years after the procedure. (13-15)

• The STAR trial was a prospective, open-label study in which the 158 patients served as their own controls, each having failed a prior cartilage repair procedure.
• At 48 months follow-up, intent-to-treat analysis showed 76% of patients having achieved good to excellent results while 24% were considered failures.
• The authors reported that there was no relationship between the size of the lesion at baseline and treatment outcomes with ACI.
• Subsequent surgical procedures on the index knee related to ACI were required in 40% of patients; these procedures included debridement of cartilage lesion (31%), lysis of adhesions (14%), other debridement (10%), meniscectomy (6%), loose body removal (5%), microfracture of the index lesion (5%) and scar tissue removal (5%).
• The most common cause for a subsequent surgical procedure was periosteal patch hypertrophy.
• The majority (61%) of patients who had a subsequent surgical procedure went on to have successful results, while 39% were eventually considered treatment failures.

The remaining data in the current published literature consists of unreliable case series, registry data, studies comparing various ACI techniques, and retrospective reviews that do not permit scientific conclusions on the effects of ACI compared with other surgical and non-surgical procedures. (16-19)

Joints other than the knee

Current literature on ACI in joints other than the knee is limited to very small case series that do not permit scientific conclusion on the effect of this procedure on pain, functional levels and the delay or elimination of the need for further surgical procedures. (20-22)

Safety

Knee

Randomized, controlled trials reported between-group differences in postoperative swelling, functional levels, cartilage quality and the need for subsequent surgical procedures.

• ACI resulted in mixed hyaline cartilage and fibrocartilage compared to osteochondral autograft (e.g., mosaicplasty) which retained its hyaline character. Fibrocartilage has less capability than hyaline cartilage to withstand shock or shearing force and can degenerate over time, often resulting in the return of clinical symptoms.
• Due to its invasiveness, ACI was related to greater swelling and worse functional level scores than less invasive procedures (e.g., microfracture, microabrasion)
• Additional procedures (e.g., anterior cruciate ligament replacement, meniscectomy and lateral release) were required in the majority of patients.

The authors of the STAR trial reported a high rate of adverse events related to ACI and a 40% rate of subsequent surgical procedures. (13-15)

• Over half of the study population (54%) experienced at least one serious adverse event secondary to ACI.
• Adverse events included arthrofibrosis (16%), graft overgrowth (15%), chondromalacia or chondrosis (12%), graft complications (i.e., fraying or fibrillation, 10%), graft delamination (6%) and joint adhesion (5%).
• Forty percent of patients underwent subsequent surgical procedures on the index knee related to ACI.
• Subsequent surgical procedures included debridement of cartilage lesion (31%), lysis of adhesions (14%), other debridement (10%), meniscectomy (6%), loose body removal (5%), microfracture of the index lesion (5%) and scar tissue removal (5%).
• The majority (61%) of patients who had a subsequent surgical procedure went on to have successful results, while 39% were eventually considered treatment failures.

Joints other than the knee

The safety of ACI for the treatment of cartilage defects of joints other than the knee is unknown; current literature on ACI in joints other than the knee is limited to very small case series that do not permit scientific conclusion. (20-22)

References

1. BlueCross and BlueShield Association Medical Policy Reference Manual, Policy No. 7.01.48
2. BlueCross and BlueShield Association Technology Evaluation Center. Autologous Chondrocyte Transplantation of the Knee, 2003; Vol. 18, No. 2
3. BlueCross and BlueShield Association Technology Evaluation Center. Autologous Chondrocyte Transplantation, 1996; Vol.11 Tab 8
4. BlueCross and BlueShield Association Technology Evaluation Center. Autologous Chondrocyte Transplantation, 1997; Vol. 12 Tab 26
5. BlueCross and BlueShield Association Technology Evaluation Center Autologous Chondrocyte Transplantation, 2000; Vol. 15 Tab 12
6. Visna P, Pasa L, Cizmar et al. Treatment of deep cartilage defects of the knee using autologous chondrocyte transplantation and by abrasive techniques – a randomized controlled study. Acta Chir Belg 2004;104(6):709-14
7. Saris DB, Vanlauwe J, Victor J et al. Characterized chondrocyte implantation results in better structural repair when treating symptomatic cartilage defects of the knee in a randomized controlled trial versus microfracture. Am J Sports Med 2008;36(2):235-46
   
8. Knutsen G, Engebretsen L, Ludvigsen TC et al. Autologous chondrocyte implantation compared with microfracture in the knee. J Bone Joint Surg 2004;86-A(3):455-463
   
9. Knutsen G, Drogset JO, Engebretsen L et al. A randomized trial comparing autologous chondrocyte implantation with microfracture. Findings at five years. J Bone Joint Surg Am 2007;89(10):2105-12
   
10. Horas U, Pelinkovic D, Herr G et al. Autologous chondrocyte implantation and osteochondral cylinder transplantation in cartilage repair of the knee joint. J Bone Joint Surg 2003;85(2):185-192
    
11. Bentley G, Biant RW, Carrington J et al. A prospective, randomised comparison of autologous chondrocyte implantation versus mosaicplasty for osteochondral defects in the knee. J Bone Joint Surg 2003;85-B:223-30
    
12. Dozin B, Malpeli M, Cancedda R et al. Comparative evaluation of autologous chondrocyte implantation and mosaicplasty: a multi centered randomized clinical trial. Clin J Sport Med 2005;15(4):220-6
    
13. Cole BJ Cole BJ, Brewster R, DerBerardino T, et al. Improvement in Symptoms and Function after Autologous Chondrocyte Implantation (ACI, Carticel®) in Patients who Failed Prior Treatment, Results of the Study of Treatment of Articular Repair (STAR). AOSSM July 2007. Available online at http://www.sportsmed.org/tabs/education/downloads/AM2007%20Final %20Abstracts.pdf. (Verified 2/17/09)
    
14. Genzyme Biosurgery. Carticel Prescribing Information, 2007. Available at http://www.genzyme.com/business/biosurgery/biosurg_home.asp(Verified 2/17/09)
    
15. Zaslav K, Cole B, Brewster R, et al. A prospective study of autologous chondrocyte implantation in patients with failed prior treatment for articular cartilage defect of the knee: results of the study of the treatment of articular repair (STAR) clinical trial. Am J Sports Med 2008 Oct 16. [Epub ahead of print]
    
16. Browne JE, Anderson AF, Arciero R et a. Clinical outcome of autologous chondrocyte implantation at 5 years in US subjects. Clin Orth Rel Res 2005;436:237-45
    
17. Rosenberger RE, Gomoll AH, Bryant T, et al. Repair of Large Chondral Defects of the Knee With Autologous Chondrocyte Implantation in Patients 45 Years or Older. Am J Sports Med 2008 Aug 25. [Epub ahead of print]
    
18. Farr J. Autologous chondrocyte implantation improves patellofemoral cartilage treatment outcomes. Clin Orthop Relat Res 2007;463:187-94
    
19. Henderson IJ, Lavigne P. Periosteal autologous chondrocyte implantation for patellar chondral defect in patients with normal and abnormal patellar tracking. Knee 2006;13(4):274-9
    
20. Koulalis D, Schulz W, Heyden M. Autologous chondrocyte transplantation for osteochondritis dissecans of the talus. Clinic Orthop 2002;395:186-92
    
21. Giannini S, Buda R, Grigolo B et al. Autologous chondrocyte transplantation in osteochondral lesions of the ankle joint. Foot Ankle Int 2001;96:513-7
22. Nam EK, Ferkel RD, Applegate GR. Autologous chondrocyte implantation of the ankle: a 2- to 5-year follow-up. Am J Sports Med. 2009;37(2):274-84. Epub 2008 Dec 22

Cross References

Meniscal Allograft Transplantation, Regence Medical Policy Manual, Surgery, Policy No. 71

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