Given that epidural steroid injections tend to afford lumbar radiculopathy patients only partial, short-term pain relief, investigators have been in search of an epidural agent that is more effective.1 TNF-alpha is a well-known inflammatory mediator that is known to play a role in lumbar radiculopathy, and etanercept is a TNF-alpha inhibitor that has been effective in the treatment of rheumatologic disorders. As such, etanercept is a promising candidate as a next-generation epidural agent that could provide better results than epidural steroids. Dr. Freeman and his colleagues from Australia published the results from their industry-sponsored, small scale, double-blinded multicenter RCT comparing 3 different doses of epidural etanercept to placebo for the treatment of acute lumbar radiculopathy caused by a herniated disk in the November 1 issue. There were approximately 10 patients in each group, and all patients had MRI-confirmed lumbar disk herniation and radiculopathy. They received 2 transforaminal injections two weeks apart of either saline or etanercept. The results are quite interesting and demonstrated a clinically and statistically significant benefit for the lowest dose etanercept group(0.5 mg) compared to placebo for leg and back pain. The higher doses (2.5 mg and 12.5 mg) were associated with a smaller, less consistently significant benefit. Very striking was that 50% of patients in the low dose etanercept group reported no pain at 4 weeks compared to none of the patients in the placebo group. While this was a relatively small study, the data do suggest a potential benefit of low dose epidural etanercept.
The authors have done a nice job performing a double-blinded randomized controlled trial for a problem that is difficult to study given the acuity of the pain and patients’ tendency to crossover to other treatment options if the study treatment is not effective. Additionally, they created a very well-defined patient cohort with lumbar radiculopathy attributable to an MRI-confirmed disk herniation. Studies in the past have had much looser inclusion and exclusion criteria, making it difficult to know to which patients their results could be applied. The inverse dose response curve demonstrated by this study is interesting and suggests that lower doses yield better results, though the mechanism responsible for this is unclear. Earlier RCTs comparing etanercept to epidural steroids have provided conflicting results, with one study suggesting some benefit to etanercept in stenosis patients with another demonstrating an advantage for steroids in radiuculopathy patients.2,3 Given these conflicting results, the jury remains out on epidural etanercept. However, the current report which includes a very well-defined disk herniation cohort with radiculopathy is promising. Hopefully the next step will be a large-scale pivotal trial comparing epidural etanercept, steroids, and saline in disk herniation patients to determine if etanercept represents an improvement. Such a study would also provide Level 1 data about the efficacy of epidural injections in general, as the current literature suggests they typically provide only short-term, partial relief.
Please read Dr. Freeman’s article on this in the November 1 issue. Are you optimistic about the potential for epidural etanercept in lumbar disk herniation patients with radiculopathy? Let us know by leaving a comment on The Spine Blog.
Adam Pearson, MD, MS
Associate Web Editor
1. Pinto RZ, Maher CG, Ferreira ML, et al. Epidural corticosteroid injections in the management of sciatica: a systematic review and meta-analysis. Annals of internal medicine 2012;157:865-77.
2. Cohen SP, White RL, Kurihara C, et al. Epidural steroids, etanercept, or saline in subacute sciatica: a multicenter, randomized trial. Annals of internal medicine 2012;156:551-9.
3. Ohtori S, Miyagi M, Eguchi Y, et al. Epidural administration of spinal nerves with the tumor necrosis factor-alpha inhibitor, etanercept, compared with dexamethasone for treatment of sciatica in patients with lumbar spinal stenosis: a prospective randomized study. Spine 2012;37:439-44.