Dr. Pasquale X. Montesano is the principal Orthopedic Spine surgeon at Montesano Spine & Sport. After receiving a Bachelor of Science degree from Siena College and then attending medical school at New York Medical College in Valhalla, NY, Dr. Montesano completed extensive postgraduate training and has worked towards achieving... more
Published January 3, 2017
Orthopedics and Rheumatology
Volume 4, Issue 2-January 2017
Intradiscal Injection of an Autologous Alpha-2-Macroglobulin (A2M) Concentrate Alleviates Back Pain in FAC-Positive Patients
Pasquale X Montesano MD, *Jason M Cuellar MD, PhD, Gaetano J Scuderi MD
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 3- and 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 3- and 6-months in FACT-positive patients compared to 9.4 +/- 11.9 and 12.6 +/- 11.8 points at 3- and 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.
Keywords: Biologic; Disc; Alpha 2 Macroglobulin; A2M; Back Pain; APIC; FAC; FACT
Abbreviations: FAC: Fibronectin-Aggrecan Complex; DDD: Degenerative Disc Disease; A2M: Alpha-2-Macroglobulin; ODI: Oswestry Disability Index; VAS: Visual Analog Scores; APIC: Autologous Protease Inhibitor Concentrate; MCID: Minimal Clinically important Difference; CLBP: Chronic Low Back Pain; MRI: Magnetic Resonance Imaging; HNP: Herniated Nucleus Pulposus; IRB: Institutional Review Board; ELISA: Enzyme-Linked Immune Sorbent Assay; OD: Optical Density; TMB: Tetra Methyl Benzidine; ANOVA: Analysis of Variance; ADAMTS: A Disintegrin-like And Metalloproteinase with Thrombo Spondin; MMPs: Matrix Metalloproteinase’s; PDGF-BB: Platelet-Derived Growth Factor-BB; bFGF: basic Fibroblast Growth Factor; VEGF: Vascular Endothelial Growth Factor; TGF-B1: Transforming Growth Factor-Beta1