RESEARCH - Tests of TNF inhibitors for sciatica continue

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Tests of TNF inhibitors for sciatica continue

Rheumawire

January 26, 2006

Janis

Tours, France - Both mechanical and chemical factors contribute to

development of radiculopathy associated with disk herniation, and while TNF-

is part of the story, it isn't the whole story. Dr Philippe Goupille

(Hôpital Trousseau, Tours, France) writes in the February 2006 issue of

ls of the Rheumatic Diseases [1] that despite good theoretical

underpinnings and excellent results in open-label pilot studies, the first

controlled trial of a TNF inhibitor in sciatica did not find much treatment

effect [2].

" Although the rationale appears to be sound, there is no proof of the

efficacy of such a treatment, and its use still has not been validated, "

Goupille says.

Disappointing RCT results raise interesting new questions

Among the factors that suggested a potential benefit from use of TNF

inhibitors in disk-herniation-associated radiculopathy are:

" Chemical " effects of herniated nucleus pulposus (NP) material that

resemble effects of TNF-.

Blocking of these effects by doxycycline and partial blocking by

anti-TNF monoclonals.

Sensitization by TNF- of nerve roots that have been subjected to

mechanical stress.

Presence of TNF- in neurons and Schwann cells.

" TNF- appears to be able to sensitize the nerve root to pain when the latter

has previously been subjected to mechanical stress, a hypothesis that is

compatible with current understanding of the physiopathology of disk-induced

sciatica, " Goupille writes.

Following good results in two open-label studies of infliximab (Remicade,

Centocor) infusion in patients with sciatica and MRI-proven disk herniation,

the first randomized, controlled, double-blind trial comparing infliximab (5

mg/kg) with placebo was undertaken by Korhonen et al.

This trial, dubbed the Finnish Infliximab Related Study (FIRST II), was

meant to confirm 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, " The results of this

randomized trial do not support the use of infliximab for lumbar radicular

pain in patients with disk-herniation-induced sciatica. "

Goupille notes that the methodology of this study has been criticized due to

its heterogeneous population, small group size, and use of only one

infusion. " The response might have been influenced by the intensity of the

radicular pain, the duration of evolution, or the anatomical localization of

the disk herniation, " he says.

" Might TNF- be only one of the pieces in the puzzle, and might anti-TNF- be

beneficial only if used in combination with drugs blocking other cytokines?

Might TNF- have a role only in the initial stages of sciatica, and might

anti-TNF- be effective only at an early stage? " Goupille asks.

Some of these questions might be answered later this year, when results of

two ongoing controlled studies of adalimumab (Humira, Abbott) for treatment

of sciatica are expected.

Sources

1. Goupille P, Mulleman D, Valat JP. Radiculopathy associated

with disc herniation. Ann Rheum Dis 2006; 65:141-143.

2. 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.

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Mayo Clinic in Rochester

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s Hopkins Medicine

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