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Randomized, Double-blind, Placebo-Controlled, Trial of Transforaminal Epidural Etanercept for the Treatment of Symptomatic Lumbar Disc Herniation

Freeman, Brian J. C., FRCS (Tr & Orth), FRACS (Ortho), DM*,†; Ludbrook, Guy L., FANZCA, PhD*,†; Hall, Stephen, FRACP; Cousins, Michael, FANZCA, FFPMANZCA§; Mitchell, Bruce, FACSP, FACSM, MPainMed; Jaros, Mark, PhD; Wyand, Michael, DVM, PhD**; Gorman, James R., MD, PhD**

doi: 10.1097/01.brs.0000435140.61593.4c
Randomized Trial

Study Design. Multicenter, randomized, double-blind, placebo-controlled trial.

Objective. To examine the safety and efficacy of three different doses of the tumor necrosis factor alpha (TNF-α) inhibitor etanercept versus placebo for the treatment of symptomatic lumbar disc herniation (LDH).

Summary of Background Data. TNF-α is considered to be a major cause of radicular leg pain associated with symptomatic LDH. Systemic administration of TNF-α inhibitors for sciatica has indicated a trend toward efficacy.

Methods. Forty-nine subjects aged between 18 and 70 years, with persistent lumbosacral radicular pain secondary to LDH, and an average leg pain intensity of 5/10 or more were randomized to 1 of 4 groups: 0.5-mg, 2.5-mg, 12.5-mg etanercept, or placebo. Subjects received 2 transforaminal epidural injections, 2 weeks apart, and were assessed for efficacy up to 26 weeks after the second injection. The primary outcome measure was the change in mean daily worst leg pain (WLP). Secondary outcomes included average leg pain, worst back pain, average back pain, in-clinic pain, Oswestry Disability Index, patient global impression of change, and tolerability.

Results: Forty-three of the 49 randomized patients completed the study. Patients receiving 0.5-mg etanercept showed a clinically and statistically significant (P< 0.1) reduction in mean daily WLP compared with the placebo cohort from 2 to 26 weeks for both the per protocol population (−5.13 vs. −1.95; P= 0.066) and the intention-to-treat population (−4.40 vs. −1.84; P= 0.058). Fifty percent of these subjects reported a 100% reduction in WLP 4 weeks post-treatment compared with 0% of subjects in the placebo cohort. Improvements in all secondary outcomes were also observed in the 0.5-mg etanercept cohort. The overall incidence of adverse events was similar in placebo and all etanercept cohorts.

Conclusion. Two transforaminal injections of etanercept provided clinically significant reductions in mean daily WLP and worst back pain compared with placebo for subjects with symptomatic LDH. Epidural etanercept may offer patients with sciatica a safe and effective nonoperative treatment.

Level of Evidence: N/A

This randomized controlled trial compared 2 transforaminal injections of the tumor necrosis factor alpha-a inhibitor etanercept to placebo for subjects with severe sciatica. Clinically and statistically significant reductions in mean daily worst leg were observed in subjects receiving etanercept compared with placebo. Epidural etanercept could offer patients with sciatica a safe and effective nonoperative treatment.

*Royal Adelaide Hospital, Adelaide, Australia

University of Adelaide, Adelaide, Australia

Cabrini Medical Centre, Melbourne, Australia

§Royal North Shore Hospital, Sydney, Australia

Metro Spinal Clinic, Melbourne, Australia

Summit Analytical, Chicago, IL; and

**BioAssets Development Corporation, Wellesley, MA.

Address correspondence and reprint requests to Brian J. C. Freeman, FRCS (Tr & Orth), FRACS (Ortho), DM, Spinal Unit, Level 4, North Wing, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000, Australia; E-mail:

Acknowledgment date: October 17, 2012. Revision date: June 24, 2013. Acceptance date: July 15, 2013.

The device(s)/drug(s) that is/are the subject of this manuscript is/are not FDA-approved for this indication and is/are not commercially available in the United States.

BioAssets Development Corporation, now a wholly-owned subsidiary of Teva Pharmaceuticals Industries Ltd., funds were received in support of this work.

Relevant financial activities outside the submitted work: consultancy, employment, grants, payment for lecture, stocks.

© 2013 by Lippincott Williams & Wilkins