TNF inhibitors and sciatica

by Nathan Wei, MD, FACP, FACR

Nathan Wei is a nationally known board-certified rheumatologist and author of the Second Opinion Arthritis Treatment Kit. It's available exclusively at this website... not available in stores.

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Both chemical and mechanical factors appear to contribute to the development of radiculopathy associated with disk herniation.

The use of TNF-alpha inhibitors has been tested for this condition. While impressive results were seen in open-label pilot studies, the first controlled trial of a TNF inhibitor in sciatica did not find a significant treatment effect (Korhonen T, Karppinen J, Paimela L, et al. The treatment of disc herniation-induced sciatica with infliximab: results of a randomized, controlled, 3-month follow-up study. Spine 2005; 30:2724-2728)

Among factors that are hypothesized to occur with the use of TNF inhibitors in disk-herniation-associated radiculopathy are:

• Chemical effects of herniated nucleus pulposus material that resemble effects of TNF-alpha.
• Blocking of these effects by both doxycycline as well as by anti-TNF monoclonal antibodies.
• Sensitization by TNF-alpha of nerve roots that have undergone mechanical stress.
• Presence of TNF-alpha in neurons and Schwann cells.

TNF-alpha seems to sensitize the nerve root to pain when the latter has previously been subjected to mechanical stress.

The first randomized, controlled, double-blind trial comparing infliximab (5 mg/kg) with placebo was undertaken by Korhonen et al.

This trial [Finnish Infliximab Related Study (FIRST II)], was meant to test the efficacy of a single infusion of infliximab for sciatic pain. Forty patients with unilateral moderate to severe sciatic pain and MRI-verified disk herniation were randomized to a single infusion of either infliximab or placebo. The primary end point was a reduction in leg pain from baseline to 12 weeks.

The investigators found significant reductions in leg pain in both groups, with no significant difference between treatment regimens. Seven patients in each group required surgery. The researchers concluded that "The results of this randomized trial do not support the use of infliximab for lumbar radicular pain in patients with disk-herniation-induced sciatica."

The methodology of this study was criticized by some investigators because of its heterogeneous population and small group size.

Other possibilities ventured by some include the need to combine anti-TNF therapies with other drugs, the need to use more than one infusion, or perhaps the need to use anti-TNF drugs earlier.

Further studies, I believe, are planned with other anti-TNF drugs.

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