Daniel Saris1, Andrew Price2, Wojciech Widuchowski3, Marion Bertrand-Marchand4, Jacob Caron5, Jon Olav Drogset6, Pieter Emans7, Ales Podskubka8, Anika Tsuchida9, Sven Kili10, David Levine11, Mats Brittberg12. 1. University Medical Center Utrecht, Utrecht, the Netherlands Reconstructive Medicine, Tissue Regeneration, MIRA Institute, University of Twente, Enschede, the Netherlands d.saris@umcutrecht.nl. 2. NIHR Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK. 3. District Hospital of Orthopedics and Trauma Surgery, Department of Knee Surgery, Arthroscopy and Sports Traumatology, Piekary Slaskie, Poland. 4. Chirurgie Arthrose, Sport et Arthroscopie, Polyclinique Saint Roch, Montpellier, France. 5. St Elisabeth Ziekenhuis, Afdeling Orthopedie, Tilburg, the Netherlands. 6. Department of Orthopaedics, Trondheim University Hospital, Trondheim, Norway. 7. Academisch Ziekenhuis Maastricht, Afdeling Orthopedie, Maastricht, the Netherlands. 8. First Faculty of Medicine, Charles University in Prague, Hospital Bulovka, Prague, Czech Republic. 9. University Medical Center Utrecht, Utrecht, the Netherlands. 10. Genzyme Biosurgery (now Sanofi Biosurgery), Oxford, UK. 11. Genzyme Biosurgery (now Sanofi Biosurgery), Cambridge, Massachusetts, USA. 12. Region Halland Orthopedics, Kungsbacka Hospital, Kungsbacka, Sweden.
Abstract
BACKGROUND: Randomized controlled trials studying the efficacy and safety of matrix-applied characterized autologous cultured chondrocytes (MACI) versus microfracture (MFX) for treating cartilage defects are limited. PURPOSE: To compare the clinical efficacy and safety of MACI versus MFX in the treatment of patients with symptomatic cartilage defects of the knee. STUDY DESIGN: Randomized controlled clinical trial; Level of evidence, 1. METHODS:Patients enrolled in the SUMMIT (Demonstrate the Superiority of MACI implant to Microfracture Treatment) trial had ≥1 symptomatic focal cartilage defect (Outerbridge grade III or IV; ≥3 cm(2)) of the femoral condyles or trochlea, with abaseline Knee Injury and Osteoarthritis Outcome Score (KOOS) pain value <55. The co-primary efficacy endpoint was the change in the KOOS pain and function subscores from baseline to 2 years. Histological evaluation and magnetic resonance imaging (MRI) assessments of structural repair tissue, treatment failure, the remaining 3 KOOS subscales, and safety were also assessed. RESULTS: Of the 144 patients treated, 137 (95%) completed the 2-year assessment. Patients had a mean age of 33.8 years and a mean lesion size of 4.8 cm(2). The mean KOOS pain and function subscores from baseline to 2 years were significantly more improved with MACI than with MFX (pain: MACI, 37.0 to 82.5 vs MFX, 35.5 to 70.9; function: MACI, 14.9 to 60.9 vs MFX, 12.6 to 48.7; P = .001). A significant improvement in scores was also observed on the KOOS subscales of activities of daily living (MACI, 43.5 to 87.2 vs MFX, 42.6 to 75.8; P < .001), knee-related quality of life (MACI, 18.8 to 56.2 vs MFX, 17.2 to 47.3; P = .029), and other symptoms (MACI, 48.3 to 83.7 vs MFX, 44.4 to 72.2; P < .001) for patients treated with MACI compared with MFX. Repair tissue quality was good as assessed by histology/MRI, but no difference was shown between treatments. A low number of treatment failures (nonresponders: MACI, 12.5% vs MFX, 31.9%; P = .016) and no unexpected safety findings were reported. CONCLUSION: The treatment of symptomatic cartilage knee defects ≥3 cm(2) in size using MACI was clinically and statistically significantly better than with MFX, with similar structural repair tissue and safety, in this heterogeneous patient population. Moreover, MACI offers a more efficacious alternative than MFX with a similar safety profile for the treatment of symptomatic articular cartilage defects of the knee.
RCT Entities:
BACKGROUND: Randomized controlled trials studying the efficacy and safety of matrix-applied characterized autologous cultured chondrocytes (MACI) versus microfracture (MFX) for treating cartilage defects are limited. PURPOSE: To compare the clinical efficacy and safety of MACI versus MFX in the treatment of patients with symptomatic cartilage defects of the knee. STUDY DESIGN: Randomized controlled clinical trial; Level of evidence, 1. METHODS:Patients enrolled in the SUMMIT (Demonstrate the Superiority of MACI implant to Microfracture Treatment) trial had ≥1 symptomatic focal cartilage defect (Outerbridge grade III or IV; ≥3 cm(2)) of the femoral condyles or trochlea, with a baseline Knee Injury and Osteoarthritis Outcome Score (KOOS) pain value <55. The co-primary efficacy endpoint was the change in the KOOS pain and function subscores from baseline to 2 years. Histological evaluation and magnetic resonance imaging (MRI) assessments of structural repair tissue, treatment failure, the remaining 3 KOOS subscales, and safety were also assessed. RESULTS: Of the 144 patients treated, 137 (95%) completed the 2-year assessment. Patients had a mean age of 33.8 years and a mean lesion size of 4.8 cm(2). The mean KOOS pain and function subscores from baseline to 2 years were significantly more improved with MACI than with MFX (pain: MACI, 37.0 to 82.5 vs MFX, 35.5 to 70.9; function: MACI, 14.9 to 60.9 vs MFX, 12.6 to 48.7; P = .001). A significant improvement in scores was also observed on the KOOS subscales of activities of daily living (MACI, 43.5 to 87.2 vs MFX, 42.6 to 75.8; P < .001), knee-related quality of life (MACI, 18.8 to 56.2 vs MFX, 17.2 to 47.3; P = .029), and other symptoms (MACI, 48.3 to 83.7 vs MFX, 44.4 to 72.2; P < .001) for patients treated with MACI compared with MFX. Repair tissue quality was good as assessed by histology/MRI, but no difference was shown between treatments. A low number of treatment failures (nonresponders: MACI, 12.5% vs MFX, 31.9%; P = .016) and no unexpected safety findings were reported. CONCLUSION: The treatment of symptomatic cartilage knee defects ≥3 cm(2) in size using MACI was clinically and statistically significantly better than with MFX, with similar structural repair tissue and safety, in this heterogeneous patient population. Moreover, MACI offers a more efficacious alternative than MFX with a similar safety profile for the treatment of symptomatic articular cartilage defects of the knee.
Authors: Artur Kroell; Paul Marks; Jaskarndip Chahal; Mark Hurtig; Tim Dwyer; Daniel Whelan; John Theodoropoulos Journal: Knee Surg Sports Traumatol Arthrosc Date: 2014-12-23 Impact factor: 4.342
Authors: James D Wylie; Melissa K Hartley; Ashley L Kapron; Stephen K Aoki; Travis G Maak Journal: Clin Orthop Relat Res Date: 2015-05 Impact factor: 4.176
Authors: Eleftherios A Makris; Andreas H Gomoll; Konstantinos N Malizos; Jerry C Hu; Kyriacos A Athanasiou Journal: Nat Rev Rheumatol Date: 2014-09-23 Impact factor: 20.543
Authors: Aaron J Krych; Ayoosh Pareek; Alexander H King; Nick R Johnson; Michael J Stuart; Riley J Williams Journal: Knee Surg Sports Traumatol Arthrosc Date: 2016-08-18 Impact factor: 4.342
Authors: Mackenzie L Sennett; Gregory R Meloni; Alexandra J E Farran; Hans Guehring; Robert L Mauck; George R Dodge Journal: J Orthop Res Date: 2018-07-26 Impact factor: 3.494