Boston, Mass. (Apr. 7) -- Thalidomide (ThalomidR) may be safe and effective for refractory radiculopathic pain, according to an open-label trial presented at the 24th Annual Scientific Meeting of the American Pain Society.

"The exciting thing about thalidomide is that it works against inflammatory cytokines, and we are learning more and more about how many painful disorders are initiated and maintained by these chemicals," says study author Aimee C. Chagnon, MD, director of clinical research and teaching at the Pain Management Center of the University of California at San Francisco. Increasing evidence indicates that this immunomodulator is active in treating various neuropathic pain conditions and is an effective inhibitor of tumor necrosis factor-alpha (TNF-α).

Dr. Chagnon pointed out that, in addition to neuroinflammatory conditions such as reflex sympathetic dystrophy (RSD), thalidomide "can also work for things like migraines, [as well as] rheumatic conditions like rheumatoid arthritis, ankylosing spondylitis, and other such disorders," she says. "We have found in our research that there is also promise in postherpetic neuralgia, which is not surprising, since these cytokines are active in this disorder, too."

Thalidomide was banned in the 1960s when it was found to have severe teratogenic effects. At the time, it was widely used as a sleeping pill and to treat morning sickness during pregnancy, which resulted in thousands of birth defects. In 1998, the US Food and Drug Administration (FDA) approved its use for the treatment of the debilitating and disfiguring lesions associated with erythema nodosum leprosum, a complication of leprosy. It is also being studied as a treatment for a number of other conditions, including weight loss and aphthous ulcers in AIDS patients, macular degeneration, and several types of cancer.

 

Pain relieving effects can be "life-altering"

In the study presented by Dr. Chagnon, 18 patients with radiculopathic pain initially received thalidomide at 50 mg/day, administered in the evening. The dose was titrated in 50 mg increments per month up to a maximum of 200 mg/day based on tolerability and clinical response. All patients completed the System for Thalidomide Education and Prescribing Safety (S.T.E.P.S.) oversight program. This program provides extensive patient education about the risks associated with thalidomide, requires a 100% patient registry, and helps ensure a zero-tolerance policy for thalidomide exposure during pregnancy.

The average course of therapy in the study lasted 2.6 months at a dose of 131 mg/day. Most patients responded within 6 weeks, typically at doses of 100 mg/day or above. Of the initial 18 patients, 13 were evaluable at the end of the study period and 62% responded within a range of 15-100% improvement on a visual analog scale (VAS). Two patients improved 15-25%, three patients improved 26-50%, and three patients improved 51-100%. This last group characterized their pain relief as "life-altering."

Moreover, two patients were able to eliminate all heavy opioid use and in nine of the 13 patients sleep improved to a greater degree than pain. Thalidomide-treated patients showed average 13% and 25% benefits on the Beck Depression Inventory (BDI) and the Short Form McGill Pain Questionnaire (SFMPQ), respectively.

"The side effects of thalidomide are somnolence and constipation, which are very similar to opiates, but dramatically different from COX-2 [inhibitors]," Dr. Chagnon tells CIAOMed. "The big difference is that it can cause what appears to be an autoimmune-induced peripheral neuropathy, which is novel," she says. This condition arose in three of 13 patients. Other expected side effects of thalidomide use occurred in this study, including sedation, constipation, dizziness, and edema, but all were managed by dose modification or withdrawal from the study.

 

Biologics may also treat RSD

Going forward, Dr. Chagnon says that she is hoping to investigate the role of anakinra. adalimumab, infliximab, and etanercept for RSD. "We know TNF and other inflammatory cytokines (in the case of anakinra, IL-1) are important in the genesis and maintenance of pain, [and] I and others are surprised no one else has really looked at these," she says. "I strongly believe these agents should be made more widely available for such neuroinflammatory conditions as RSD, radicular pain, postherpetic neuralgia, and the like," she points out. "The real stumbling block in the US is payment from insurance companies [for unapproved indications]."

Reference:

Chagnon AC. Thalidomide for the Treatment of Refractory Radiculoptahic Pain: An Open-Label Trial. Presented at: the 24th Annual Scientific Meeting of the American Pain Society; March 30-April 2, 2005; Boston, Massachusetts. Session 313.