BOSTON, Massachusetts—The jury is out on whether TNF-blockers have a role in treating sciatica induced by disc herniation, according to a review article in the December issue of Arthritis & Rheumatism.¹

"TNF-α seems to have a role only in the initial stage of sciatica, thus challenging its use as treatment for disc herniation-induced sciatica in humans," conclude researchers led by Philippe Goupille, MD, of the Hôpital Trousseau, Tours, France. "Available results from controlled studies with anti-TNF-blocking agents in humans are disappointing and evidence from current controlled studies is therefore eagerly awaited."

TNF-blockade for sciatica makes sense, in theory

The theoretical underpinning for the use of TNF-blockers in this setting is that the herniated nucleus pulposus (NP) is thought to secrete proinflammatory substances (including TNF-α) that could induce an autoimmune reaction in disc herniation, the researchers point out. These might provoke functional and structural abnormalities of the nerve root.

Animal studies support this theory, but TNF-α offers only a partial explanation. "Several substances other than TNF-α may explain the effect of NP in these experiments, the study authors write.

But is TNF-α really secreted by injured discs in humans?

While some studies in human intervertebral discs have shown that TNF-α is a component of NP, others have shown no TNF secretion. What's more, no study has shown that levels of TNF-α are any higher in herniated discs from patients with radiculupathy than in patients with degenerative disc disease without radiculupathy.

One randomized controlled trial of 40 patients with disc herniation-associated sciatica that compared infliximab (Remicade®) and placebo proved "inconclusive," the study authors write. In that study, a single infusion of 5 mg/kg of infliximab was no better than placebo in terms of pain symptoms or functional handicap, number of days on sick leave, and number of discectomies.

While there are some safety issues with TNF-blockade, the risk could be lower when these agents are used to treat sciatica as it would likely entail an abridged course of therapy. Animal studies suggest that the local production of endogenous TNF-α occurs at an early stage of the disease process and is short-lived.

Translating research into practice

"It's been tossed out as an idea to use a brief application of TNF-inhibitors to treat sciatica induced by disc herniation," said Philip J. Mease, MD, with the department of internal medicine at the Swedish Medical Center and Rheumatology Associates, in Seattle, Washington. "There is some theoretical interest, but it remains to be investigated adequately," he told MSKreport.com

"In practice, sometimes patients with acute sciatica or cervical radiculupathy will respond to courses of prednisone, so by the same principle, some of the same inflammatory cytokines and chemokines activated in context of an acute disc herniation could at least theoretically [be reduced by] an anti-TNF therapy," he concluded.

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