scholarly journals Autologous chondrocyte implantation in the knee: systematic review and economic evaluation

2017 ◽  
Vol 21 (6) ◽  
pp. 1-294 ◽  
Author(s):  
Hema Mistry ◽  
Martin Connock ◽  
Joshua Pink ◽  
Deepson Shyangdan ◽  
Christine Clar ◽  
...  

BackgroundThe surfaces of the bones in the knee are covered with articular cartilage, a rubber-like substance that is very smooth, allowing frictionless movement in the joint and acting as a shock absorber. The cells that form the cartilage are called chondrocytes. Natural cartilage is called hyaline cartilage. Articular cartilage has very little capacity for self-repair, so damage may be permanent. Various methods have been used to try to repair cartilage. Autologous chondrocyte implantation (ACI) involves laboratory culture of cartilage-producing cells from the knee and then implanting them into the chondral defect.ObjectiveTo assess the clinical effectiveness and cost-effectiveness of ACI in chondral defects in the knee, compared with microfracture (MF).Data sourcesA broad search was done in MEDLINE, EMBASE, The Cochrane Library, NHS Economic Evaluation Database and Web of Science, for studies published since the last Health Technology Assessment review.Review methodsSystematic review of recent reviews, trials, long-term observational studies and economic evaluations of the use of ACI and MF for repairing symptomatic articular cartilage defects of the knee. A new economic model was constructed. Submissions from two manufacturers and the ACTIVE (Autologous Chondrocyte Transplantation/Implantation Versus Existing Treatment) trial group were reviewed. Survival analysis was based on long-term observational studies.ResultsFour randomised controlled trials (RCTs) published since the last appraisal provided evidence on the efficacy of ACI. The SUMMIT (Superiority of Matrix-induced autologous chondrocyte implant versus Microfracture for Treatment of symptomatic articular cartilage defects) trial compared matrix-applied chondrocyte implantation (MACI®) against MF. The TIG/ACT/01/2000 (TIG/ACT) trial compared ACI with characterised chondrocytes against MF. The ACTIVE trial compared several forms of ACI against standard treatments, mainly MF. In the SUMMIT trial, improvements in knee injury and osteoarthritis outcome scores (KOOSs), and the proportion of responders, were greater in the MACI group than in the MF group. In the TIG/ACT trial there was improvement in the KOOS at 60 months, but no difference between ACI and MF overall. Patients with onset of symptoms < 3 years’ duration did better with ACI. Results from ACTIVE have not yet been published. Survival analysis suggests that long-term results are better with ACI than with MF. Economic modelling suggested that ACI was cost-effective compared with MF across a range of scenarios.LimitationsThe main limitation is the lack of RCT data beyond 5 years of follow-up. A second is that the techniques of ACI are evolving, so long-term data come from trials using forms of ACI that are now superseded. In the modelling, we therefore assumed that durability of cartilage repair as seen in studies of older forms of ACI could be applied in modelling of newer forms. A third is that the high list prices of chondrocytes are reduced by confidential discounting. The main research needs are for longer-term follow-up and for trials of the next generation of ACI.ConclusionsThe evidence base for ACI has improved since the last appraisal by the National Institute for Health and Care Excellence. In most analyses, the incremental cost-effectiveness ratios for ACI compared with MF appear to be within a range usually considered acceptable. Research is needed into long-term results of new forms of ACI.Study registrationThis study is registered as PROSPERO CRD42014013083.FundingThe National Institute for Health Research Health Technology Assessment programme.

Cartilage ◽  
2018 ◽  
Vol 10 (3) ◽  
pp. 305-313 ◽  
Author(s):  
Peter Cornelius Kreuz ◽  
Richard Horst Kalkreuth ◽  
Philipp Niemeyer ◽  
Markus Uhl ◽  
Christoph Erggelet

2006 ◽  
Vol 15 (1) ◽  
pp. 61-66 ◽  
Author(s):  
Masataka Deie ◽  
Yoshio Sumen ◽  
Nobuo Adachi ◽  
Atsuo Nakamae ◽  
Ayato Miyamoto ◽  
...  

2019 ◽  
Vol 7 (9) ◽  
pp. 232596711986821 ◽  
Author(s):  
Vegard Fossum ◽  
Ann Kristin Hansen ◽  
Tom Wilsgaard ◽  
Gunnar Knutsen

Background:Autologous matrix-induced chondrogenesis (AMIC) is a single-stage alternative to autologous chondrocyte implantation for treatment of localized cartilage defects of the knee. To our knowledge, no randomized controlled trial exists comparing the 2 methods.Purpose:To evaluate any difference in the outcome of AMIC as compared with collagen-covered autologous chondrocyte implantation (ACI-C).Study Design:Randomized controlled trial; Level of evidence, 2.Methods:A prospective randomized controlled clinical trial was designed to assess any differences in the outcomes between ACI-C and AMIC for the treatment of ≥1 chondral or osteochondral defects of the distal femur and/or patella. The inclusion period was set to 3 years, and the aim was to include 80 patients (40 in each group). Patient inclusion was broad, with few exclusion criteria. The primary outcome was change in Knee injury and Osteoarthritis Outcome Score (KOOS) at 2 years as compared with baseline. The secondary outcomes were the number of failures in each group at 2 years and the change in KOOS subscale, Lysholm, and pain visual analog scale (VAS) scores at 2 years as compared with baseline. A 2-sample t test with a significance level of P < .05 was used to compare the change in score from baseline between groups.Results:A total of 41 patients over 3 years were included in the study: 21 in the ACI-C group and 20 in the AMIC group. All the patients had prior surgery to the index knee. At 2-year follow-up, the clinical scores for both groups improved significantly from baseline. No significant differences between groups were seen in the change from baseline for KOOS (AMIC, 18.1; ACI-C, 10.3), any of the KOOS subscales, the Lysholm score (AMIC, 19.7; ACI-C, 17.0), or the VAS pain score (AMIC, 30.6; ACI-C, 19.6). Two patients in the AMIC group had progressed to a total knee replacement by the 2-year follow-up as compared with none in the ACI-C group.Conclusion:At 2-year follow-up, no significant differences were found regarding outcomes between ACI-C and AMIC. Mid- and long-term results will be important.Registration:NCT01458782 ( ClinicalTrials.gov identifier).


2017 ◽  
Vol 45 (12) ◽  
pp. 2751-2761 ◽  
Author(s):  
Takahiro Ogura ◽  
Brian A. Mosier ◽  
Tim Bryant ◽  
Tom Minas

Background: Treating articular cartilage defects is a demanding problem. Although several studies have reported durable and improved clinical outcomes after autologous chondrocyte implantation (ACI) over a long-term period, there is no report with over 20 years’ follow-up. Purpose: To evaluate clinical outcomes after first-generation ACI for the treatment of knees with disabling, large single and multiple cartilage defects for which patients wished to avoid prosthetic arthroplasty, with a minimum of 20 years’ follow-up. Study Design: Case series; Level of evidence, 4. Methods: The authors reviewed prospectively collected data from 23 patients (24 knees; mean age, 35.4 years [range, 13-52 years]) undergoing ACI for the treatment of symptomatic, full-thickness articular cartilage lesions. A mean of 2.1 lesions per knee were treated over a mean total surface area of 11.8 cm2 (range, 2.4-30.5 cm2) per knee. Kaplan-Meier survival analysis and functional outcome scores, including the modified Cincinnati Knee Rating System, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Short Form–36 (SF-36), were used. Patients also self-reported an improvement in pain with a visual analog scale and a satisfaction survey. Results: The 20-year survival rate was 63% (95% CI, 40%-78%). The evaluation of the 15 knees with retained grafts demonstrated that all clinical scores except the WOMAC subscore for stiffness and SF-36 mental component summary score improved significantly and were sustained to 20 years postoperatively. Ninety-three percent of these patients rated knee-specific outcomes as good or excellent. The outcomes for 9 of 24 knees were considered failures, including 5 undergoing revision ACI and 4 being converted to arthroplasty at a mean of 1.7 and 5.9 years, respectively. Only 1 of 5 knees that underwent revision ACI was converted to arthroplasty at 1.9 years after the index surgery, and the other 4 patients were able to maintain their biological knee. Overall, 20 years later, 79% of patients maintained their native knee, for which they initially sought treatment, and were satisfied when evaluated. Conclusion: First-generation ACI provided satisfactory survival rates and significant clinical improvements over a 20-year follow-up, which offers an important standard for comparison with newer-generation ACI technologies of the future.


2020 ◽  
Vol 48 (9) ◽  
pp. 2230-2241
Author(s):  
Alexander Barié ◽  
Patrizia Kruck ◽  
Reza Sorbi ◽  
Christoph Rehnitz ◽  
Doris Oberle ◽  
...  

Background: Matrix-associated autologous chondrocyte implantation (MACI) is a further development of the original autologous chondrocyte implantation periosteal flap technique (ACI-P) for the treatment of articular cartilage defects. Purpose: We aimed to establish whether MACI or ACI-P provides superior long-term outcomes in terms of patient satisfaction, clinical assessment, and magnetic resonance imaging (MRI) evaluation. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: A total of 21 patients with cartilage defects at the femoral condyle were randomized to MACI (n = 11) or ACI-P (n = 10) between the years 2004 and 2006. Patients were assessed for subjective International Knee Documentation Committee (IKDC) score, Lysholm and Gillquist score, Tegner Activity Score, and 36-Item Short Form Health Survey (SF-36) preoperatively (T0), at 1 and 2 years postoperatively (T1, T2), and at the final follow-up 8 to 11 years after surgery (T3). Onset of osteoarthritis was determined using the Kellgren-Lawrence score and Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score, and delayed gadolinium-enhanced MRI of cartilage was used to evaluate the cartilage. Adverse events were recorded to assess safety. Results: There were 16 patients (MACI, n = 9; ACI-P, n = 7) who were reassessed on average 9.6 years after surgery (76% follow-up rate). The Lysholm and Gillquist score improved in both groups after surgery and remained elevated but reached statistical significance only in ACI-P at T1 and T2. IKDC scores increased significantly at all postoperative evaluation time points in ACI-P. In MACI, IKDC scores showed a significant increase at T1 and T3 when compared with T0. In the majority of the patients (10/16; MACI, 5/9; ACI-P, 5/7) a complete defect filling was present at the final follow-up as shown by the MOCART score, and 1 patient in the ACI-P group displayed hypertrophy of the repair tissue, which represents 6% of the whole study group and 14.3% of the ACI-P group. Besides higher SF-36 vitality scores in ACI-P at T3, no significant differences were seen in clinical scores and MRI scores between the 2 methods at any time point. Revision rate was 33.3% in MACI and 28.6% in ACI-P at the last follow-up. Conclusion: Our long-term results suggest that first- and third-generation ACI methods are equally effective treatments for isolated full-thickness cartilage defects of the knee. With the number of participants available, no significant difference was noted between MACI and ACI-P at any time point. Interpretation of our data has to be performed with caution due to the small sample size, which was further limited by a loss to follow-up of 24%.


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