Medical Policy: 07.01.64
Original Effective Date: May 2014
Reviewed: February 2018
Revised: February 2018
Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.
This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.
ACI (Autologous Chondrocyte Implant): ACI is a two-step procedure. New cartilage cells are grown and then implanted in the cartilage defect.
First, healthy cartilage tissue is removed from a non-weight bearing area of the bone. This step is done as an arthroscopic procedure. The tissue which contains healthy cartilage cells, or chondrocytes, is then sent to the laboratory. The cells are cultured and increase in number over a 3 to 5-week period.
An open surgical procedure, or arthrotomy, is then done to implant the newly grown cells. The cartilage defect is prepared. A layer of bone-lining tissue, called periosteum, is sewn over the area. This cover is sealed with fibrin glue. The newly grown cells are then injected into the defect under the periosteal cover.
ACI is most useful for younger patients who have single defects larger than 2 cm in diameter. ACI has the advantage of using the patient's own cells, so there is no danger of a patient rejecting the tissue. It does have the disadvantage of being a two-stage procedure that requires an open incision. It also takes several weeks to complete.
The culturing of chondrocytes is considered by the FDA to fall into the category of manipulated autologous structural (MAS) cells, which are subject to a biologic licensing requirement. At the present time, only Carticel™ (Genzyme) has received FDA approval for the culturing of chondrocytes through a biologics license. In 1997, Carticel received FDA approval for the repair of clinically significant, “...symptomatic cartilaginous defects of the femoral condyle (medial lateral or trochlear) caused by acute or repetitive trauma.…” The labeled indication was revised in October 1999 to read as follows:
“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.” Thus, the revised labeling suggests a more restricted use of autologous chondrocytes, i.e., as a second-line therapy after failure of initial arthroscopic or surgical repair. In 2017, production of Carticel® was phased out and MACI® is the only ACI product that is available in the United States.
MACI®, (Vericel) autologous cultured chondrocytes on porcine collagen membrane), a product that was FDA approved in December 2016, an alternative to autologous cultured chondrocytes and growth with Carticel. MACI is intended for autologous use and must only be administered to the patient for whom it was manufactured. The implantation of MACI is to be performed via an arthrotomy to the knee joint under sterile conditions. The amount of MACI administered is dependent upon the size (surface in cm²) of the cartilage defect. The implantation membrane is trimmed by the treating surgeon to the size and shape of the defect, to ensure the damaged area is completely covered, and implanted cell-side down.
MACI is contraindicated in patients with a known history of hypersensitivity to gentamicin, other aminoglycosides, or products of porcine or bovine origin. MACI is also contraindicated for patients with severe osteoarthritis of the knee, inflammatory arthritis, inflammatory joint disease, or uncorrected congenital blood coagulation disorders. MACI is also not indicated for use in patients who have undergone prior knee surgery in the past 6 months, excluding surgery to procure a biopsy or a concomitant procedure to prepare the knee for a MACI implant. MACI is contraindicated in patients who are unable to follow a physician-prescribed post-surgical rehabilitation program. The safety of MACI in patients with malignancy in the area of cartilage biopsy or implant is unknown. Expansion of present malignant or dysplastic cells during the culturing process or implantation is possible. Patients undergoing procedures associated with MACI are not routinely tested for transmissible infectious diseases. A cartilage biopsy and MACI implant may carry the risk of transmitting infectious diseases to healthcare providers handling the tissue. Universal precautions should be employed when handling the biopsy samples and the MACI product. The MACI implant is not recommended during pregnancy. For implantations post-pregnancy, the safety of breast feeding to infant has not been determined.
Per the manufacturer, and FDA indications for use: The use of MACI in pediatric patients (younger than 18 years of age) or patients over 65 years of age has not been established. The use in this approved age group is directly from inclusion in the SUMMIT trial, which was used to gain FDA approval for MACI. The manufacturer plans on studying the pediatric population with further studies. Vericel proposed the following timeline for the completion of the clinical pediatric study: Protocol submission, by June 30, 2017; study initiation, by June 30, 2018; study completion by June 30, 2025; and submission of the final report by December 31, 2025.
A number of second-generation methods for implanting autologous chondrocytes in a biodegradable matrix are currently in development/testing. These include Atelocollagen (collagen gel, Koken), BioCart II (ProChon Biotech, Phase II trial), Bioseed C (polymer scaffold, BioTissue Technologies) CaReS (collagen gel, Ars Arthro), Cartilix (polymer hydrogel, Cartilix), Cartipatch (solid scaffold with an agarose-alginate matrix, TBF Tissue Engineering, Phase III trial), Chondron (fibrin gel, Sewon Cellontech), Hyalograft C (hyaluronic acid-based scaffold, Fidia Advanced Polymers), NeoCart (ACI with a 3-dimensional chondromatrix, Histogenics. Phase III trial), and Novocart (collagen-chondroitin sulfate scaffold, B. Braun-Tetec). ChondroCelect (characterized chondrocyte implantation, TiGenex, Phase III trial completed) uses a gene marker profile to determine in vivo cartilage-forming potential and thereby optimizes the phenotype (e.g., hyaline cartilage vs. fibrocartilage) of the tissue produced with each ACI implantation cell batch. Each batch of chondrocytes is graded based on the quantitative gene expression of a selection of positive and negative markers for hyaline cartilage formation. Although clinical use of these second-generation ACI products has been reported in Europe and Asia, nly MACI is approved for use in the U.S. at this time.
In a 2010 clinical practice guideline on the diagnosis and treatment of osteochondritis dissecans (OCD), the American Academy of Orthopaedic Surgeons (AAOS) was unable to recommend for or against a specific cartilage repair technique in symptomatic skeletally immature or mature patients with an unsalvageable osteochondritis dissecans lesion.
NICE issued an updated Technology Appraisal Guidance (2005 and reviewed in 2008). The NICE guidance cited insufficient evidence to determine the benefits of autologous chondrocyte implantation and indicated this technology “should not be used for the treatment of articular cartilage defects except where the treatment is part of a clinical study.” The guidance noted many limitations in available trial data including length of follow-up, comparison to conservative treatment, assessment of the quality of cartilage produced, and the impact of cartilage produced on functional outcomes and health-related quality of life.
In a 2016 guideline by the working group “Clinical Tissue Regeneration” of the German Society of Orthopaedics and Trauma entitled “Autologous chondrocyte implantation (ACI) for cartilage defects of the Knee” indications for ACI include:
Softening and swelling
Fragmentation and fissures in area less than 0.5 inch in diameter
Fragmentation and fissures in area larger than 0.5 inch in diameter
Exposed subchondral bone
Source: Campbell's Operative Orthopaedics, 2007
Carticel® has been phased out and MACI® is the only ACI product that is available in the United States.
Autologous chondrocyte implantation (also referred to as autologous chondrocyte transplant/ACT), or matrix induced chondrocyte implantation (MACI), may be considered medically necessary for the treatment of disabling full thickness articular cartilage defects of the femoral condyle (medial, lateral, or trochlear) caused by acute or repetitive trauma, in the following patients:
For surgical repair of the defect greater than 4cm2
Previous inadequate response to arthroscopic or other surgical repair of the defect (microfracture, drilling) for all defects 2cm2-4cm2
Additionally ALL of the following criteria must be met:
The use of MACI for individuals less than 18 years of age have not been proven, per FDA product indications “The safety and effectiveness of MACI in pediatric patients have not been established”.
Repeat autologous chondrocyte implantation for the same lesion is considered not medically necessary.
If the procedure does not meet all the medical criteria above, the culturing of chondrocytes will not meet medical criteria.
Autologous chondrocyte implantation for treatment of, but not limited to, patellar chondromalacia, osteoarthritis, osteochondral dessicans (OCD), inflammatory disease of the joints, is investigational.
Autologous chondrocyte implants are investigational for patellar or talar lesions or lesions of other joints (e.g., hip and shoulder) and all other indications because the effectiveness of autologous chondrocyte implants for these lesions has not been established or FDA approved.
The use of non-FDA approved second-generation methods for implanting autologous chondrocytes in a biodegradable matrix is investigational for the treatment of osteochondral defects/lesions and all other indications because their effectiveness has not been established. This includes second generation products, ChondroCelect, Novocart, NeoCart, Hyalograft C, Chondron, Cartilix and Bioseed. The main deficiency of the existing evidence is that there are no published controlled studies that compare the outcomes of autologous chondrocyte implant with any other treatments or with the natural progression of the disease. The available studies do report the proportions of patients treated with ACT who achieved various levels of outcomes, but there is no way to determine if those outcomes are better than, the same as, or worse than, the outcomes that would have occurred with other treatments.
The use of autologous chondrocyte implantation and the MACI® (autologous cultured chondrocytes on porcine collagen membrane) procedure as a first line treatment is considered investigational for smaller defects (<4cm2). Although the studies show promise that the procedures may be more beneficial than microfracture, only short term outcomes are available. Additional well-designed studies involving larger study populations and long-term follow-up are needed to determine the role of ACI/MACI relative to microfracture A 2016 Cochrane review evaluated surgical interventions (microfracture, drilling, AOT, allograft transplantation) for the treatment of isolated cartilage defects of the knee in adults. Three RCTs selected compared autologous transplant to microfracture for isolated cartilage defects. The evidence was considered of very low quality with high or unclear risk of bias.
To report provider services, use appropriate CPT* codes, Modifiers, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or diagnosis codes.
Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc. They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.
*CPT® is a registered trademark of the American Medical Association.