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.