Trial of TNF inhibitors for slipped-disc sciatica urged

[Guest guest]

Rheumawire

Feb 6, 2004

Trial of TNF inhibitors for slipped-disc sciatica urged

Manchester, UK - Surgery promises a quick fix for low back pain caused

by a herniated intervertebral disc (HID), but follow-up studies have

shown that the early advantage fades over the next 2-4 years. TNF

inhibitors might be a more durable alternative, and without the

operative hazards and risk of " post-surgical back pain syndrome. "

A pilot study of infliximab for relief of HID-related sciatica was so

promising and laboratory studies of disc-derived TNF so compelling that

a large randomized, placebo-controlled trial is warranted, according to

an editorial by Drs RG and AJ Freemont in the February 2004 issue

of Rheumatology [1].

" The exciting experimental results described for TNF-alpha suggest that

a basic science approach may at last have succeeded in identifying a

therapeutic target capable of potentially altering the natural history

of HID-related sciatica, and thus outcome, " they write.

If successful, such a trial might shift the care of herniated discs away

from surgery and physiotherapy-based triage and toward care by

rheumatologists.

and Freemont argue that a large randomized controlled trial of

TNF-inhibitor treatment for patients with acute/subacute HID-associated

sciatica is now appropriate for three reasons. The first is research

showing that TNF-alpha applied directly to the spinal nerve roots causes

vascular and radicular abnormalities like those seen when nerves are

exposed to nucleus pulposus material. The second is evidence that

nucleus pulposus expresses TNF-alpha. The third is the pilot study by

Karppinin et al showing that a single dose of the TNF inhibitor

infliximab produced long-term relief of sciatica pain [2].

" A randomized controlled trial would have to be of acute/subacute HID

patients, ie <3 months duration, and the HID would have to be clinically

and radiologically fully matched, " tells rheumawire. says

that the study design should include examination of other potential

factors in pain persistence, which afflicts only a minority of patients

with low back pain.

Among the possibilities are degree of TNF-alpha-induced nerve root

damage and damage control mechanisms; degree of nerve-root scarring and

scar control mechanisms; psychological factors, and individual variation

in the expression of genes for TNF-alpha and for profibrotic cytokines.

" A genetic study is clearly required to answer the possibility that

genetics may govern HID outcome. This could possibly be done at the same

time as a randomized, controlled trial of TNF inhibition, " says.

The TNF-alpha data follow a number of what describes as " false

dawns " in terms of explaining the root mechanisms of HID-associated

nerve root pain. These have included nerve root inflammation, defective

fibrinolysis, intraspinal inflammation, and ischemic damage due to

venous outflow obstruction.

If the efficacy of TNF inhibition is confirmed to reduce the severity

and persistence of HID-associated radicular pain, the savings in health

and welfare costs could be enormous. " If TNF-alpha blockade renders

decompressive surgery mostly redundant in HID except when mandatory, as

in acute cauda equina syndrome, spinal surgeons may understandably

consider HID a non-surgical problem. Thus, HID patients might in the

future be triaged non-surgicallyprobably by rheumatologists, given their

growing expertise with TNF-alpha blockade, " the authors write.

Meanwhile, sees no major reason a single dose of a TNF inhibitor

(such as the 3 mg/kg dose of infliximab used in the Karppinen study)

might not be tried in selected patients. " My suspicion is that TNF

blockade would not help chronic patients, but I see no reason for

rheumatologists not to use TNF blockers on an empirical basis, so long

as their hospital/university base hospital has no objection, " he says.

Janis

Sources

1. RG, Freemont AJ. TNF-alpha blockade for herniated

intervertebral disc-induced sciatica: a way forward at last?

Rheumatology 2004; 43:119-121.

2. Karppinin J, Korhonen T, Malmivaara A et al. Tumor necrosis

factor-alpha monoclonal antibody, infliximab, used to manage severe

sciatica. Spine 2004; 28:750-3.

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org