April 19, 2012 — Epidural injections of steroids or the cytokine inhibitor etanercept (Enbrel; Immunex) were not much better than epidural saline injections in relieving leg and back pain in a new multicenter, randomized, controlled study of adults with subacute sciatica.
Epidural steroid injections are commonly used for lumbosacral radiculopathy, "yet, studies are decidedly mixed regarding their effectiveness," study investigator Steven P. Cohen, MD, from Johns Hopkins School of Medicine, Baltimore, Maryland, told Medscape Medical News.
On the basis of the new study, epidural steroid injections "may provide modest short-term pain relief for some adults with lumbosacral radiculopathy, but larger studies with longer follow-up are needed to confirm their benefits," the study team concludes.
Their report was published April 17 in Annals of Internal Medicine.
Etanercept Findings 'Disappointing'
Dr. Cohen said the results with etanercept were "somewhat surprising and disappointing. Unlike steroids, etanercept addresses the underlying cause of many cases of sciatica from a herniated disc by directly blocking the inflammatory molecules responsible for the pain. In animal studies, cytokine inhibitors have been shown to prevent nerve injury from a herniated disc, and a small pilot study in humans yielded very auspicious results," he explained.
The current study enrolled 84 adults (mean age, 42 years) with lumbosacral radiculopathy lasting more than 4 weeks but 6 months or less and leg pain that was more than or as severe as back pain. Conservative therapy had failed in all patients, and they all had imaging evidence of a pathologic disc condition correlating with symptoms (eg, herniated disc or annular tear).
They were randomly allocated in a 1:1:1 ratio to 2 epidural steroid injections of methylprednisolone acetate, 60 mg, plus 0.5 mL of saline (for a total volume of 2 mL); 2 epidural etanercept injections (4 mg reconstituted in 2 mL of sterile water); or 2 mL normal saline.
All injections were mixed with 0.5% bupivacaine and separated by 2 weeks. The segmental level at which the patient was injected was chosen according to symptoms and radiologic findings. Pharmacists prepared the syringes, and patients and physicians were blinded to treatment assignment.
The primary outcome measure was a numeric rating scale score of 0 to 10 for leg pain 1 month after the second injection. Mean baseline scores for leg pain were similar in the 3 groups: 5.71, 6.62, and 6.31 in the steroid, etanercept, and saline groups, respectively.
The investigators say leg and back pain improved in all groups. The largest reductions in leg pain occurred in the steroid group. The reductions in scores for back pain were "less profound" than those for leg pain.
Table 1. Within-Group Mean Change From Baseline at 1 Month for Leg and Back Pain
| Group | Change from Baseline in Leg Pain (95% Confidence Interval) | Change from Baseline in Back Pain (95% Confidence Interval) |
| Steroids | -3.57 (-4.43 to -2.71) | -2.14 (-3.23 to -1.06) |
| Etanercept | -2.98 (-4.41 to -1.55) | -1.56 (-2.83 to -0.28) |
| Saline | -2.48 (-3.59 to -1.37) | -1.07 (-1.96 to -0.17) |
Between-group differences in the primary outcome measure of leg pain at 1 month also favored epidural steroids over etanercept and saline, but the differences were modest and did not reach statistical significance.
Table 2. Between-Group Differences in Leg Pain at 1 Month
| Comparison | Between-Group Differences (95% Confidence Interval) | P Value |
| Steroids vs saline | -1.26 (-2.79 to 0.27) | .11 |
| Etanercept vs saline | -0.25 (-1.80 to 1.30) | .56 |
| Steroids vs etanercept | -1.01 (-2.60 to 0.58) | .21 |
For back pain, smaller between-group differences favoring steroids compared with saline and etanercept were seen.
At 1 month, both the steroid and saline groups experienced "sizable improvements" in functional capacity based on the Oswestry Disability Index (ODI), whereas the etanercept group reported little change or worsening; this was largely due to worsening in the sections for sleep and sex life, the investigators say. One patient in the etanercept group experienced a clinically significant deterioration in function manifested by a 30-point increase in the ODI score, they note.
Table 3. Mean Change in ODI Score at 1 Month
| Comparison | Mean Change (95% Confidence Interval) | P Value |
| Steroids vs saline | -5.87 (-15.59 to 3.85) | .23 |
| Etanercept vs saline | 10.29 (0.55 to 20.04) | .04 |
| Steroids vs etanercept | -16.16 (-26.05 to -6.27) | .002 |
Placebo Effect?
According to the study team, more patients treated with epidural steroids (75%) reported 50% or greater leg pain relief and a positive global perceived effect at 1 month than those who received saline (50%) or etanercept (42%) (P = .09).
Patients in the study whose condition improved at 1 month remained blinded and were assessed at 3 and 6 months. "Of interest, slightly more patients in the saline (40%) and etanercept (38%) groups had a positive outcome at 6 months than did those in the steroid group (29%), which resulted from a greater recurrence rate in the steroid group."
"The most probable explanation for this finding," the authors write, "is that a higher proportion of successful outcomes in patients who did not receive steroids was due to a placebo effect, which is very powerful for pain-alleviating procedures and can persist for months or even years (that is, longer than the effects of epidural injections)."
Summing up the findings, Dr. Cohen told Medscape Medical News there was a "trend for steroids to be better than both (etanercept and saline) in the short term (at 1-month), but not long term (3 and 6 months)."
"At the low doses administered (which were found to be effective in the pilot study), epidural etanercept was no better than saline. However, our findings cannot rule out that higher doses might be more effective, or that longer-acting cytokine inhibitors could provide longer relief," he added.
A study published last month in the journal Spine showed that a much higher dose of epidural etanercept was better than steroids at 2 weeks, but not at 4 weeks. "The downside of using higher doses is that they might suppress the immune system," Dr. Cohen said.
In addition to a "possibly subtherapeutic dose of etanercept," other limitations to the study include short-term follow-up and small sample size. "Another consideration that could enhance outcomes would be to allow for more injections on an as-needed basis, as is frequently done in clinical practice and controlled studies," the researchers say.
There is "an urgent need to identify safer and more effective treatments" for sciatica, Dr. Cohen concludes.
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