Purpose

Patient’s specific characteristics may play a role in determining clinical outcome after cartilage regenerative procedures. The objective of this analysis was to reveal if any correlation existed among patient’s characteristics and clinical outcome in the context of a RCT comparing an aragonite-based scaffold to debridement/microfractures for treating joint surface lesions.

Methods and Materials

A large RCT was performed in 26 medical centers, involving 167 subjects who underwent aragonite-based (Agili-C™, CartiHeal Ltd., Israel) scaffold implantation and 84 subjects who underwent arthroscopic debridement/microfractures (control) for the treatment of chondral/osteochondral knee defects. For each treatment group, the influence of age, sex, BMI, previous ligament reconstruction, pre-injury activity level and smoking history were analyzed to detect if a correlation existed in regards to the clinical outcome, up to the final evaluation at 24 months’ follow-up.

Results

Scaffold superiority over debridement/microfractures was confirmed across all sub-groups and covariates analysis. In the scaffold group, comparable clinical benefit was obtained in subjects younger or older than 50yy (p<0.0001). Moreover, the regenerative approach provided satisfactory outcome even in subjects older than 65yy, although their number in the present cohort was small. Differences between scaffold and control groups were much higher in females than in males, suggesting that the former, who usually present poorer prognosis after cartilage surgery, are good candidates for the aragonite-based implant. In the scaffold group, subjects with BMI lower or higher than 30 presented similar KOOS score improvement at 24 months, with better results than control even in obese patients. Previous ligament reconstruction and smoking history did not negatively influence the scaffold group. Considering pre-injury activity level, the comparison revealed particular advantage for the scaffold in non-active subjects.

Conclusion

The aragonite-based scaffold’s superiority over control was confirmed across all subgroups and covariates. Its efficacy was not influenced by sex, age, BMI, previous ligament surgery, smoking history and activity level.

Purpose

The purpose of this study is to evaluate long term follow-up of single injection of nSTRIDE® APS for the treatment of unilateral knee osteoarthritis (NCT02138890).

Methods and Materials

Forty-six patients underwent a 2:1 randomization process to either one single injection of APS(n=31) or salin (n=15). APS was prepared with the nSTRIDE APS Kit (Zimmer Biomet). Data up to the 3 year follow up were previously published(1). The APS cohort was asked to participate in unblinded 60-month follow-up and the saline patients were offered cross-over after 12 months and were similarly followed. Efficacy endpoints (WOMAC LK 3.1, KOOS, and VAS) were measured as a change from baseline to each time point. Data is presented as mean ± SD. Missing data was calculated as baseline carried forward(BLCF) for subjects that had exited the trial for knee OA pain.

Results

At the final follow-up for the study (60 months), 17 of the original 31 randomized to APS and 6 of the original 15 saline/crossover remained in the study. The Kaplan-Meier curve for subjects exiting for knee-related events demonstrate a 0.64 survivorship probability[95% CI 0.463,0.820](Figure 1). Using the BLCF method, the APS cohort had a mean WOMAC pain percent improvement from baseline of 64.8±29.5% at 1 year(p<0.0001), 50.4±42.1% at 3 years(p<0.0001), and 39.0±41.2% at 5 years(p<0.0001). For the subjects that accepted crossover after 1 year, the WOMAC pain improvement was 45.5±33.3% at time of crossover(p=0.0002), 44.0±37.6% at 3 years(p=0.0008), and 24.6±33.7% at 5 years(p=0.028).

Conclusion

All in all, treatment with a single, intra-articular injection of APS in subjects with knee osteoarthritis has shown long-lasting pain and function relief and indicates of the long-term durability APS for knee osteoarthritis.

[1]Kon et al. AJSM;2020;48(11):2703-2710.

Purpose

The purpose of this study is to compare the safety and effectiveness of a single injection of nSTRIDE® APS and Synvisc-One® Hyaluronic Acid for unilateral knee osteoarthritis(NCT03182374).

Methods and Materials

Subjects with knee OA Kellgren-Lawrence 2-4(n=252) were randomized 1:1 to receive a single injection of APS or HA. Endpoints included WOMAC pain, function, stiffness, and quality of life as well as safety and change in X-ray. After 12 months, subjects were allowed a blinded second injection choice(no injection, same injection, or crossover). This analysis follows subjects for 24 months.

Results

Nine APS subjects and 16 HA subjects exited early (prior to 12-months) due to issues related to knee OA. Both groups had a significant improvement in pain from baseline with no significant difference between groups(APS:41.1 ± 34.6%;HA:40.4 ± 33.5%). Both groups had similar improvements in function, stiffness, NRS pain, EQ-5D, and responder rates. Use of restricted medication for knee OA was 8.8% in the APS group and 12.2% in the HA group at their 12-month visit. There was no difference in overall adverse event reporting between groups. At the 24-month time point, subjects that chose no second injection maintained similar pain reduction as their 12-month time point(change 0.4 for APS and -0.7 for HA). APS subjects requesting a second “same” injection had a statically significant improvement in pain at 24 months(change -1.0;p=0.03) while the HA subjects receiving the “same” second injection did not significantly improve(change -1.1;p=0.09). Subjects receiving cross over treatment did not show significant improvement from 12-month pain scores(change -1.5 for APS and -0.2 for HA). Of the original 41 subjects selecting crossover treatment, 16 rated no preference between injections while 18 preferred APS and 7 preferred HA(p=0.0417).

Conclusion

Both APS and HA improved knee OA symptoms at 12-months post injection. Subjects receiving a second APS injection statistically improved from 12 to 24 months.