The four main trials8,35,43,100described in this review all show some superiority of various forms of ACI over
MF, but in different timescales and to different degrees. The Basad8and SUMMIT100trials show clear
differences in favour of MACI by 2 years in Lysholm and KOOS, respectively. The SUMMIT trial100found no
significant difference in EQ-5D visual analogue scale (VAS) changes–both groups improved by 17 at 2 years. The TIG/ACT trial43shows superiority overall by 3 years. The ACTIVE trial35(in which ACI was a
mixture of ACI-P, ACI-C and MACI) showed no benefit in most outcome measures at 5 years, but some separation in EQ-5D after that. With the exception of EQ-5D, results are available only to 5 years in an interim analysis provided for the NICE appraisal. The ACTIVE trial35will continue to 10-year follow-up.
Previous repairs
As reported earlier, in case series previous MF appears to reduce the success of ACI. The trials reviewed above do not contribute much evidence on this. Basad did not give details of previous surgery. In TIG/ ACT43only a few (8/57) of the ACI group had had previous MF. In the SUMMIT trial,10032% of the MACI
TABLE 19 Increases in EQ-5D from baseline
Time point, years Standard care ACI
1 0.143 0.130 2 0.135 0.163 3 0.141 0.168 4 0.142 0.141 5 0.086 0.171 6 0.143 0.175 7 0.173 0.229 8 0.115 0.170
TABLE 18 The EQ-5D scores in the ACTIVE trial35
Time point, years
Standard arm ACI arm
No. of patients Mean EQ-5D No. of patients Mean EQ-5D
5 87 0.618 102 0.677
6 75 0.675 80 0.707
7 53 0.705 59 0.735
8 27 0.647 29 0.676
group had had previous repair attempts with MF, but this appeared to have little effect on response rates (no prior repairs, 90% response; more than one, 84%). In the ACTIVE trial,35almost half had a previous
repair procedure, but results are not given separately for them.
Several factors need to be considered in interpreting the evidence. First, we are somewhat reliant on subgroup analysis. Second, those who have had previous surgery may be older than those going straight to ACI, and chondrocyte viability declines with age. Third, some of the older trials had few patients who had not had prior surgery. Last, and most important, the evidence does not suggest that ACI is not worthwhile after prior MF, but only that it is not as successful. Hence there is no reason not to try ACI. Duration of symptoms
In the SUMMIT trial,100response rates were similar at 2 years: 82% for those with symptoms for less than
3 years, 92% in those with longer durations. Basad did not report results by prior duration but his MACI patients had a mean duration of symptoms of only 2.2 years. The ACTIVE trial35did not report durations.
The main evidence comes from the TIG/ACT435-year data for which only those with duration of symptoms
under 3 years showed a significant difference between ACI and MF. Improvements in KOOS at 5 years were 26 for the ACI group versus 15 for the MF group (p=0.026). For the subgroup with over 3 years’ duration, KOOS improvements were 13 for ACI and 17 for MF (not significant). This might suggest that ACI is of less value, relative to MF, in patients with longer duration.
Previous studies have shown improvements with ACI after long duration of symptoms. In the trial by Bentleyet al.,78most patients receiving ACI had excellent Cincinnati scores results despite a mean duration
of symptoms of 7.2 years. In the trial of ACI-C versus MACI by Bartlettet al.,5759% of the ACI-C group
and 72% of the MACI group had good or excellent Cincinnati scores despite duration of symptoms of approximately 10 and 7 years, respectively. In another study from Stanmore by Biantet al.,79of a cohort of
104 ACI patients followed for at least 10 years, 66% had excellent or good Cincinnati scores despite an average duration of symptoms before ACI of 7.8 years.
ACI-C or MACI?
In a very large cohort of 827 patients with mean duration of follow-up 6.2 years, Nawazet al.80reported
better results with MACI than ACI-P or ACI-C, though this was probably due to different durations, as the ACI groups came from an earlier period and so had more time for knee status to decline. The RCT of ACI-C versus MACI by Bartlettet al.57found no difference at 1 year.
In practice, ACI has evolved and most use is now expected to be MACI, with characterised chondrocytes. Predicting success
Nawazet al.80noted that the chance of success was reduced by previous attempts at repair and the presence
of any osteoarthritic change in the knee. They summarised the results from their very large cohort study thus:
Our study suggests that the‘ideal’candidate for autologous chondrocyte implantation is a younger individual with a single lesion on the trochlea or the lateral femoral condyle, with no previous procedures or evidence of degenerative changes.
At 12 years after ACI, their ideal patients had a repair survival of almost 80% compared with 50% in the whole group. Graft survival was<25% in those who had had a previous repair (including MF and mosaicplasty) and>75% in those who had not.
Survival of repairs
The 2-year differences between MF and ACI or MACI arise mainly because symptom scores reach a plateau sooner after MF than after ACI. Sariset al.70reported (from graph) that a KOOS plateau was
reached with MF by 12–18 months, whereas improvements continued after ChondroCelect ACI-P. The SUMMIT100investigators showed a plateau before 12 months with MF but not until 18 months
In the TIG/ACT trial,43Sariset al.70reported (from graph, so approximate) that about 7% of MF repairs had
failed by 20 months and 11.5% by 36 months (but based on only seven failures in the MF group). The longer-term results reported by Vanlauweet al.43showed the plateau in the KOOS in the MF group from
12 to 60 months, whereas the ChondroCelect group with duration of symptoms<3 years at surgery, reached a plateau at 36 months. The CC group with duration of symptoms of>3 years showed no difference in KOOS from MF with an early plateau and lines almost overlapping.
Basadet al.64reported that the Lysholm score in the MF group improved from 55 at baseline to 81 at
12 months, but then declined to 69 at 24 months. The MACI group had a baseline score of 55, improving to 95 at 12 months, maintained at 92 at 24 months.
Bhosaleet al.,108from Oswestry, report results at an average of 5 years (range about 3–9 years) among
80 patients, all but four having had ACI-P. The median baseline Lysholm score was 54, which improved to a median of 78 at 12 months post operation. Of the 80 patients, 65 improved and scores at 15 months were maintained for up to 9 years. They also reported that higher age, female gender and larger defect size were associated with greater benefit, but none of these associations was statistically significant. They concluded that a good result at 15 months is durable.