Efficacy of Epidural Perineural Injections With Autologous Conditioned Serum for Lumbar Radicular Compression: An Investigator-Initiated, Prospective, Double-Blind, Reference-Controlled Study

Cordelia Becker, MD; Stefan Heidersdorf, MD; Sascha Drewlo, MSc; Sonja Zirke de Rodriguez; Juergen Krämer, MD; Roland Ernst Willburger, MD

Disclosures

Spine. 2007;32(17):1803-1808. 

In This Article

Abstract and Introduction

Abstract

Study Design: Prospective, double-blind, reference-controlled, investigator-initiated, single center.
Objective: To evaluate the efficacy of Autologous Conditioned Serum (ACS; Orthokine) for the treatment of lumbar radicular compression in comparison to triamcinolone.
Summary of Background Data: Evidence from animal studies indicates that cytokines such as interleukin-1 play a decisive role in the pathophysiology of lumbar radiculopathy. ACS is enriched in the interleukin-1 receptor antagonist and other anti-inflammatory cytokines.
Methods: Thirty-two patients were treated by epidural perineural injections with ACS; 27 patients were treated with 5 mg triamcinolone and 25 patients with 10 mg triamcinolone. Treatment was applied once per week for 3 consecutive weeks and followed for 6 months. The Visual Analogue Scale (VAS) of low back pain was the primary outcome measure. The Oswestry Disability Index (ODI) was the secondary endpoint of the study. All statistical analyses were performed in an exploratory manner using SAS for Windows, version 8.2, on a personal computer. Descriptive statistics were calculated for the VAS and ODI by treatment group and time point. The data were submitted to a repeated-measurements analysis of variance with effects on treatment group, time, and treatment group-by-time interaction.
Results: Patients with lumbar back pain who were treated with ACS or the 2 triamcinolone concentrations showed a clinically remarkable and statistically significant reduction in pain and disability, as measured by patient administered outcome measurements. From Week 12 to the final evaluation at Week 22, injections with ACS showed a consistent pattern of superiority over both triamcinolone groups with regard to the VAS score for pain, but statistical significance was observed only at Week 22 in direct comparison to the triamcinolone 5 group. However, there was no statistically significant difference between the 2 triamcinolone dosages during the 6 months of the study.
Conclusion: ACS is an encouraging treatment option for patients with unilateral lumbar radicular compression. The decrease in pain was pronounced, clinically remarkable, and potentially superior to steroid injection.

Introduction

Mechanical compression of lumbar nerve roots by the protruded or herniated nucleus pulposus has been regarded as a major cause of low back pain. However, during the past decade, the important role of inflammation of the nerve roots in this disease has become better appreciated. Cytokines like interleukin-1 (IL-1) have been identified as pivotal mediators of inflammatory and degenerative changes affecting the elements of the musculoskeletal system, including the lumbar spine.[1]

Various strategies for inhibiting the biologic activities of IL-1 have been developed. In particular, the IL-1 receptor antagonist (IL-1Ra), a naturally occurring inhibitor of IL-1, has been discovered.[2,3,4] This 25-kDa glycoprotein is produced by macrophages and certain additional types of cells. It binds to the type I IL-1 receptor without initiating signal transduction, thereby blocking the biologic actions of IL-1.[5]

The efficacy of human recombinant IL-1Ra in treating rats with experimental allergic radiculitis has been assessed by comparison to prednisolone and saline.[6] Compared with saline, both treatments improved signs and symptoms of experimental polyradiculoneuropathy. Prednisolone appeared slightly more effective than IL-1Ra.

Recently, human recombinant IL-1Ra has obtained regulatory approval in the United States and Europe for the treatment of intractable rheumatoid arthritis when combined with methotrexate. Extensive Phase III clinical studies and postmarketing surveillance have confirmed the safety and effectiveness of recombinant IL-1Ra in humans.[7]

Stimulation of the endogenous production of IL-1Ra is an alternative approach to the delivery of recombinant protein. A method for increasing the autologous production of human IL-1Ra by whole venous blood has been recently described.[8] According to this method, venous blood is drawn into syringes containing CrSO4-treated glass beads. Following an incubation of 24 hours, serum is enriched in IL-1Ra by a factor of about 140 in comparison to baseline values. This increase is comparable to the one observed in cultures of purified monocytes exposed to IgG. There is no induction of IL-1ß or tumor necrosis factor (TNF)-α. In addition, incubation with glass beads for 24 hours does not lead to extensive cell death, hemolysis is mild and not clinically remarkable, and the major serum protein composition is not affected. This IL-1Ra-enriched, Autologous Conditioned Serum (ACS) is injected into the affected area, e.g., spine or knee joint, of the recipient. Based on the above principles, a medical device has been developed and marketed as Orthokine. The product has a worldwide CE-mark.

In order to explore the potential therapeutic benefit of ACS under controlled conditions, a prospective, randomized, patient- and observer-blind, reference-controlled, single-center study was performed with patients with lumbar radicular compression. Triamcinolone was used as the comparator/reference therapy. The observation period was 6 months. The study addressed the following questions:

  1. Is ACS (Orthokine) effective in the treatment of symptoms?

  2. How does ACS compare to triamcinolone, given at a standard dose (10 mg) and low dose (5 mg)?

  3. Is there any longer-term benefit from these short-term treatments?

 

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