Introduction

Autologous chondrocyte implantation (ACI) is an established technique for the treatment of cartilage lesions, particularly those greater than 2cm in size.

Content

ACI is classified as an Advanced Medicinal Therapeutic Product (ATMP) and as such its use is associated with a significant regulatory and economic burden, which is the main barrier to use. Consequently, the indications for alternate techniques (usually confined to the treatment of smaller lesions) is extended e.g AMIC, or more latterly the use of osteochondral allograft (OCA) has increased. Based on the available literature, ACI is the only technique with level one evidence demonstrating short to mid-term clinical and cost-effectiveness for the treatment of chondral lesions. Thus, ACI should be considered as the first line treatment for chondral lesions greater than 2cm.

The level of evidence available for the use of ACI in osteochondral lesions is more limited. The clinical effectiveness of ACI is known to be dependent on the integrity of subchondral bone, with inferior outcomes following previous microfracture. A number of case series have reported good outcomes with the use of ACI and bone graft (sandwich technique) for the treatment of osteochondritis dissecans, however no comparative studies currently exist. Large osteochondral lesions pose a significant clinical challenge, with some lesions unreconstructible with ACI. Excellent results for OCA have been reported for the treatment of osteochondral lesions out to 20years, however its use is largely limited by its availability. The chondrocyte viability of OCA grafts is predictive of clinical outcome, however concerns regarding the viability of grafts transported long distances from central tissue banks exist. Consequently, osteochondral lesions amenable to ACI should be treated with ACI and bone graft with OCA reserved for lesions unreconstructible with ACI or lesions known to have a poor prognosis e.g. previous microfracture.

References

Cogan CJ, Friedman J, You J, Zhang AL, Feeley BT, Ma CB, Lansdown DA. Prior Bone Marrow Stimulation Surgery Influences Outcomes After Cell-Based Cartilage Restoration: A Systematic Review and Meta-analysis. Orthop J Sports Med. 2021 Sep 24;9(9):23259671211035384. doi: 10.1177/23259671211035384. PMID: 35146031; PMCID: PMC8822078.

Familiari F, Cinque ME, Chahla J, Godin JA, Olesen ML, Moatshe G, LaPrade RF. Clinical Outcomes and Failure Rates of Osteochondral Allograft Transplantation in the Knee: A Systematic Review. Am J Sports Med. 2018 Dec;46(14):3541-3549. doi: 10.1177/0363546517732531. Epub 2017 Oct 17. PMID: 29039969.

Hevesi M, Denbeigh JM, Paggi CA, Galeano-Garces C, Bagheri L, Larson AN, Stuart MJ, Saris DBF, van Wijnen AJ, Krych AJ. Fresh Osteochondral Allograft Transplantation in the Knee: A Viability and Histologic Analysis for Optimizing Graft Viability and Expanding Existing Standard Processed Graft Resources Using a Living Donor Cartilage Program. Cartilage. 2021 Dec;13(1_suppl):948S-956S. doi: 10.1177/1947603519880330. Epub 2019 Oct 16. PMID: 31617404; PMCID: PMC8808912.

Minas T, Ogura T, Headrick J, Bryant T. Autologous Chondrocyte Implantation "Sandwich" Technique Compared With Autologous Bone Grafting for Deep Osteochondral Lesions in the Knee. Am J Sports Med. 2018 Feb;46(2):322-332. doi: 10.1177/0363546517738000. Epub 2017 Nov 10. PMID: 29125919.

Mistry H, Connock M, Pink J, Shyangdan D, Clar C, Royle P, Court R, Biant LC, Metcalfe A, Waugh N. Autologous chondrocyte implantation in the knee: systematic review and economic evaluation. Health Technol Assess. 2017 Feb;21(6):1-294. doi: 10.3310/hta21060. PMID: 28244303; PMCID: PMC5346885.

Introduction

In 2011, the Dutch Orthopedic Society (NOV) published a national guideline, including a treatment algorithm for the treatment of (osteo)chondral defects of the knee joint. This guideline was updated in 2019. This guideline was written by members of the knee working group of the NOV and acknowledged by the general board and members. The goal of this guideline was to ensure quality of the treatment of cartilage defects in the Netherlands. In the treatment algorithm, the different subtypes of (osteo)chondral defects are described, by factors like location, depth and size. The combination of these factors dictates the treatment options (Figure 1). Also, accompanying abnormalities and their influence on (osteo)chondral defects are described, like BMI, meniscal pathology, malalignment, and ligament instability. Furthermore, the criteria for expertise centers are defined.

The national guideline was used as an important foundation in the complementary approach, described below, that facilitates reimbursement of a new treatment modality for (osteo)chondral defects (in this case Autologous Chondrocyte Implantation (ACI)).

Delay in access to new therapies, after completing the technical and clinical development program and approval by EMA and/or FDA, is undesirable, especially in areas of unmet medical need. Causes for such delays are national and/or regional reimbursement procedures prior to deciding on the implementation of new therapies in the national or regional health care system. Health authorities control the access of new therapies by requiring additional evaluations on top of the regulatory approval, such as evaluation of the added value and cost-effectiveness of the new therapy versus the available, often less expensive, standard of care. New therapies, therefore, have become budgetary competitors to current standard of care. Reimbursement procedures may differ largely per country and region in terms of extensiveness and complexity of reimbursement criteria, time needed and involved stakeholders necessary for decision making. Though physicians facilitated reimbursement procedures by providing consensus statements about the position of the new therapy in the treatment algorithm and therewith determining how ‘to treat the right patient with the right therapy’, this did not always result in a positive reimbursement decision.

Content

To comply with the increased demand of health authorities and health insurers for control of the extent of the treated population and therewith budget control, we worked on a complementary approach called ‘a consensus-based implementation framework’ that facilitates the reimbursement and implementation process of new treatment options of (osteo)chondral defects (like ACI) with minimal delays.

This framework consists of a six-step approach covering assessment of added value, efficiency of the new therapy and its position in the treatment algorithm combined with determination of the organizational structure of the care in daily practice, establishing registries for outcomes and quality control measures. This treatment algorithm was described in detail in the paper guideline, which is acknowledged by all members of the NOV. One of the requirements is also that the paper guideline can be updated quickly by the same approach, so that in the future also new therapies can be introduced in the Dutch health system in the same manner.

This six-step complementary approach has been successful for implementation of autologous chondrocyte implantation for the knee in the Netherlands, which has an advanced reimbursement system, often serving as an example for other countries. The described national guideline, including the treatment algorithm is an important step in this approach. The guideline described in detail the treatment of (osteo)chondral defects of the knee and is acknowledge by all orthopedic surgeons in the Netherlands. The definition of expertise centers ensures the quality of the treatment of (osteo)chondral defects.

References

https://www.orthopeden.org/downloads/761/standpunt-chirurgische-behandeling-osteochondrale-defecten-knie.pdf

Acknowledgments

The authors like to thank Marja Pronk, Jacob Caron, Pieter Emans for their contribution to the Dutch guideline for treatment of (osteo)chondral defects of the knee and the development of the consensus-based implementation framework.