On behalf of the Federal Joint Committee (G-BA), the Institute for Quality and Efficiency in Health Care (IQWiG) investigated to what extent adults with symptomatic knee cartilage defect (but without advanced arthrosis) could benefit from autologous chondrocyte implantation (ACI) of different types: periosteal-covered (ACI-P), collagen-covered (ACI-C) or matrix-associated (M-ACI).
Cartilage tissue has a very limited ability to regenerate, and a cartilage defect is a risk factor for the development of osteoarthritis. In adults with cartilage defects that affect more than 50% of the cartilage depth or that extend to the underlying bones, ACI has been used for over 30 years. Compared to the two older methods, the ACI-C and the ACI-P, the M-ACI is the most commonly used technique today.
The ACI is a two-stage surgical method: On the first stage, the affected cartilage is removed, and the cartilage cells are cultivated to be reintroduced into the defect in the second step. The three different ACI procedures differ in terms of the reimplantation of the cultivated cells. In the M-ACI, the cultivated cartilage cells are fixed directly in a carrier matrix and inserted into the cartilage defect zone. In the two older methods, the grown cartilage cells are introduced into the cartilage defect in the form of a cell suspension and covered by the patient's periosteum (ACI-P) or a collagen membrane (ACI-C). In contrast to the M-ACI, in both methods, the cover must be fixed with seams and sealed watertight.
The study aimed to evaluate the benefit of the method of ACI (periosteal, collagen-covered, matrix-associated) compared to standard therapy in adult patients with the symptomatic defect of a circumscribed cartilage of the knee without advanced arthrosis concerning patient-relevant endpoints.
A systematic literature search was carried out in the databases MEDLINE and Cochrane Database of Systematic Reviews as well as on the websites of the National Institute for Health and Care Excellence (NICE) and the Agency for Healthcare Research and Quality (AHRQ). The search was limited to the publication date from January 2014. A systematic literature search for primary studies was carried out in the databases MEDLINE, Embase, and Cochrane Central Register of Controlled Trials.
Results – daily life activities:
- 2 studies on M-ACI showed statistically significant difference in favor of the intervention (cod16HS13: mean difference [MD]: 6.32; 95% confidence interval [95% CI]: [1.33; 11.31]; MACI00206: MD: 11.40; 95% CI: [4.60; 18.20]). However, the threshold for clinical relevance (0.2) within the confidence interval is 1 of the two studies (cod16HS13: Hedges' g: 0.5; [95% CI]: [0.10; 0.90]; MACI00206 : Hedges' g: 0.55 [95% CI]: [0.21; 0.88]). Therefore, it remains unclear whether the effect for M-ACI reaches a clinically relevant range
Results – function:
- The meta-analysis of the three studies on the M-ACI procedure showed a statistically significant difference in favor of the intervention. However, the threshold for clinical relevance (0.2) lies within the confidence interval of the pooled effect (Hedges' g: 0.44; [95% CI]: [0.03; 0.85]; p-value: 0.045). Therefore, it remains unclear whether the effect for M-ACI reaches a clinically relevant range
Results – treatment failure:
- The Bentley study (2003) demonstrated a statistically significant difference in favor of ACI-C (OR: 0.17; [95% CI]: [0.07; 0.43]; p-value: <0.001)
Data on the outcomes "mortality", "pain", "symptoms", "algofunctional index", "serious adverse events", "discontinuation due to adverse events", "health-related quality of life" did not indicate a benefit or harm from the ACI compared to standard therapy.
Comments on the published preliminary report will be viewed after the deadline (27.07.2020). If they leave questions unanswered, the respondents will be invited to an oral discussion. The IQWiG will then prepare the final report.
The preliminary report in German can be found here.
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