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

Discussion

This double-blind, randomized, reference-controlled, exploratory study in patients with unilateral lumbar radicular compression was undertaken to address the 3 issues listed in the introduction.

Regarding the efficacy of ACS, following 3 repeated epidural perineural injections at weekly intervals, both the primary efficacy measure (VAS) as well as the secondary endpoint (ODI) showed a statistically significant reduction of pain and disability compared with the baseline. Thus, ACS was effective in the treatment of symptoms caused by lumbar radicular compression.

Epidural perineural triamcinolone (as reference therapy) given as a 10-mg or 5-mg dose also reduced pain and disability. Comparisons to baseline showed a statistically significant effect. However, there was no statistically significant difference between the 2 triamcinolone dosages during the 6 months of the study.

From Week 12 to the final evaluation at Week 26, injections with ACS showed a consistent pattern of superiority over both triamcinolone groups with regard to the primary outcome measurement (VAS score for pain), but statistical significance was observed only at Week 26 in direct comparison to the triamcinolone 5 group in favor of ACS. There was no statistically significant difference between all groups with respect to the ODI.

The trial duration was 6 months, and the last assessment was performed at Week 22 after the first injection. Over the entire observation period, ACS and triamcinolone effectively, and with statistical significance, suppressed both pain and disability. There was a clear indication that ACS was superior to triamcinolone in the long-term reduction of pain.

Our data bear comparison with other, related clinical trials in the literature. When interpreting the results of this exploratory study, it has to be taken into account that patients needing early surgery because of clinical pareses or unbearable pain were excluded. This is a difference from the study of steroid injection described by Wilson-MacDonald et al,[13] which enrolled 93 patients who had been categorized as potential candidates for surgery. The mean ODI at baseline was about 40 as opposed to about 20 in the current study. Their study[13] demonstrated a significant reduction in pain early on in those patients having an epidural injection of methylprednisolone as opposed to patients having an intramuscular injection (P < 0.004). This observation thus supports epidural intervention, at least with respect to pain relief.

As an alternative to steroids, there is evidence that TNF-α injections are also effective. Korhonen et al[14] enrolled 10 patients with disc herniation-induced severe sciatica and used the need for early surgery as one endpoint of a study that examined the efficacy of infliximab, a monoclonal antibody against TNF-α. The differences significantly favored infliximab treatment.

Genevay et al[15] investigated 10 patients admitted to hospital with acute severe sciatica and showed sustained improvement after a short treatment with etanercept, another TNF-α inhibitor. Both of these studies used historical controls for comparison.

Despite differences in study objectives and patient characteristics, it is possible to compare their results to those of the current study ( Table 4 ).

As shown in Table 4 , ACS and infliximab have a roughly comparable strong effect on pain as shown by VAS at baseline and at the end of the observation period. When looking at the results for triamcinolone, it may be speculated that the effect of ACS and infliximab is clinically superior to steroid injection. ACS and infliximab act at 2 different molecular targets directly involved in nerve root inflammation.[16] It would be interesting to explore the relative contribution of IL-1 and TNF-α in nerve root inflammation and differential therapeutic options based on these different principles.

Potential complications of the epidural perineural injection technique are seldom, indeed lower and less severe than in conventional techniques, and are implicating postinjectional headaches because of inadvertent dura puncture. ACS is an autologous serum with no side effects. In comparison, the most common side effects of infliximab are upper respiratory tract infections, urinary tract infections, cough, rash, back pain, nausea, vomiting, abdominal pain, headache, weakness, and fever. Often an allergy to this drug occurs, and decreased white and red blood cell and decreased platelet counts and vasculitis have been reported with infliximab. Infections have been reported during treatment with infliximab, and it should be discontinued if a serious infection develops during treatment. Before starting infliximab, persons are recommended to have tuberculosis skin testing (PPD tests for TB) because of reports of reactivation of tuberculosis in patients taking infliximab. In controlled studies of TNF-α-blocking agents, including infliximab, more cases of lymphoma and other malignancies have been observed among patients receiving the agents than among control group patients. Therefore, ACS has potential benefits over infliximab in the mentioned cases.

The comparison between our own results and the effects of etanercept is difficult because the VAS at baseline in the etanercept study was low and patients seemed to suffer more from subjective disability than pain. The degree of disability was considerably lower in the current study compared with those described in the references.[13,14,15] It is interesting to note that chronic or acute pain does not necessarily correlate with the degree of disability across studies. According to a meta-analysis,[17] the mean ODI baseline values in the current study are representative for patients with primary back pain or spondylolisthesis. Mean values around 40 are observed in patients with chronic back pain, sciatica, or fibromyalgia. Although ACS showed a remarkable improvement of subjective disability, it would be interesting to examine its effect in patients with a higher degree of disability.

The average costs for an ACS therapy of a patient is about 1000£ for a 6-month treatment and has to be taken into account if we discuss new therapies. We know that, in some special cases, insurance carriers did already pay for this kind of therapy.

But besides all economic considerations, which always play an important role, ACS is shown to be an elegant and useful tool for the treatment of lumbar radicular compression.

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