Intradiscal Injection of an Autologous Alpha-2-Macroglobulin (A2M) Concentrate Alleviates Back Pain in FAC-Positive Patients

Objectives: A cartilage degradation product, the Fibronectin-Aggrecan complex (FAC), has been identified in patients with degenerative disc disease (DDD). Alpha-2-macroglobulin (A2M) can prevent the formation of the G3 domain of aggrecan, reducing the fibronectin-aggrecan G3 complex and therefore may be an efficacious treatment. The present study was designed to determine a. The ability of autologous concentrated A2M to relieve back pain in patients with LBP from DDD and b. The ability of FAC to predict the response to this biologic therapy. Study design/setting: Prospective cohort Patients: 24 patients with low back pain and MRI-concordant DDD Main Outcome Measurements: Oswestry disability index (ODI) and visual analog scores (VAS) were noted at baseline and at 3and 6-month follow-up. Primary outcome of clinical improvement was defined as patients with both a decrease in VAS of at least 3 points and ODI >20 points. Methods: All patients underwent lavage for molecular discography and delayed FAC analysis and injection of platelet poor plasma rich in A2M (Cytonics Autologous Protease Inhibitor Concentrate, APIC) at the time of the procedure. ANOVA with Bonferonni correction for multiple comparisons was performed. Results: Patients with FACT-positive assays were significantly more likely to show improvement in their VAS and ODI at follow-up. Mean VAS improvement in FACT-positive patients was 4.9 +/0.9 and 4.0 +/1.0 at 3 and 6-months, compared to 1.5 +/1.2 and 2.3 +/1.3 in those with negative FACT (p < 0.0001). Similarly, ODI improved on average 37 +/9.3 and 28 +/14 points at 3and 6-months in FACT-positive patients compared to 9.4 +/11.9 and 12.6 +/11.8 points at 3and 6-months in FACT-negative patients (p<0.0001).Correlation analysis demonstrated that a FACT-positive test correlates with improvement in 3-month VAS (Pearson r = 0.83; p < 0.0001) and ODI (Pearson r = 0.71; p<0.0001) and 6-month VAS (Pearson r = 0.58; p<0.0001) and ODI (Pearson r = 0.53; p<0.0001). When a 20-point ODI improvement cut-off is applied, 77% of FACT+ patients and 27% of FACT-negative patients meet this strict definition of clinical improvement. Conclusion: The results of this investigation suggest that autologous A2M may be an efficacious biologic treatment in discogenic pain and that FAC may be an important biomarker in patient selection for this treatment. Patients who are “FACT+” within the disc are more likely to demonstrate clinical improvement following intradiscal autologous A2M injection. We utilized a definition of clinical improvement that was in excess of the minimal clinically important difference (MCID). Additionally, our defined outcome measure was a combination of two universally accepted outcome parameters (ODI and VAS). The current study provides evidence for a molecular biomarker that may improve patient selection and thus clinical outcomes in the treatment of discogenic back pain. Further study utilizing placebo-controlled trial is warranted.