就腳痛方面,符合「有反應者」規範的病患,adalimumab組是安慰劑組的近兩倍(71% vs 43 %; P = .03),「少有殘留疾病影響」也是(腳痛之VAS < 20且無手術,58% vs 30%;P < .05),adalimumab組也較不需要進行椎間盤切除術(6 vs 13;P = .04)。
Adalimumab May Be Helpful for Treatment of Sciatica
By Laurie Barclay, MD
Medscape Medical News
May 27, 2010 — The tumor necrosis factor (TNF)–α inhibitor adalimumab may be helpful as adjunct treatment of sciatica, according to the results of a multicenter, randomized, double-blind, placebo-controlled trial reported online April 6 in Arthritis Rheumatism.
"The use of TNF-α blocking agents to treat radiculopathy associated with disc herniation is a topic of current interest, because of the debated pathophysiological role of proinflammatory cytokines in the development of radiculopathy induced by disc herniation," Ambrogio Capria, MD, from the Department of Internal Medicine at Tor Vergata University of Rome in Rome, Italy, told Medscape Rheumatology when asked for independent comment. "The rationale for use of anti-TNFα inhibitors in patients with sciatica is supported by the data of several experimental studies, but the clinical trials based on the administration of TNF-α inhibitors, such as infliximab and etanercept, in sciatica, have produced controversial results."
Actual Trial
Between May 2005 and December 2007, Stephane Genevay, MD, from University Hospitals of Geneva, and colleagues performed this trial in Switzerland. Inclusion criteria were lumbar disk herniation confirmed on imaging and radicular leg pain that was acute (< 12 weeks) and severe (Oswestry Disability Index [ODI] > 50).
"Patients were enrolled in the presence of sciatica for less than 12 weeks, with either a positive nerve root tension sign or a corresponding neurological deficit; disc herniation had to be confirmed by magnetic resonance imaging or computed tomography and had to correspond to clinical symptoms, as level and side," Dr. Capria said.
Exclusion criteria included a history of intolerance to adalimumab, concurrent infections, a history of cancer or tuberculosis, or sequelae of tuberculosis on chest radiographs. The study authors predefined clinically meaningful categories to reflect individual improvement, in addition to group improvement. Patients were defined as "responders" (improved by > 30% from the baseline) or with "low residual disease impact" (reaching a state of minimal and acceptable level, with a visual analog scale [VAS] score between 0 and 20 without requiring surgery).
Participants were randomly assigned to receive adjuvant therapy with 2 subcutaneous injections of 40-mg adalimumab, 7 days apart, or matching placebo. Leg pain measured by VAS (0 - 100) was the main study endpoint, which was recorded every day for 10 days and then at 6 weeks and at 6 months.
Of 265 patients screened, 61 were enrolled; 31 were randomly assigned to adalimumab, and 4 were lost to follow-up. Compared with the placebo group, the adalimumab group had more favorable evolution of leg pain with time (P < .001). However, the effect size was relatively small, with a difference of only 13.8 (95% confidence interval [CI], –11.5 to 39.0) at last follow-up.
"The overall evolution of leg pain was significantly different between the two groups, in favor of adalimumab, essentially due to a difference in evolution during the first days after therapy; the largest difference between the two treatment groups was observed at week 24, but it was not statistically significant," Dr. Capria said. "Also, the evolution of back pain was significantly different between 2 groups in favor of adalimumab (P < .0001), with the largest difference at weeks 6; in terms of back pain, at 6 months, 65% of the patients in the adalimumab group met the criteria for responders vs 27% in the placebo group (P < .01)."
Twice as many patients in the adalimumab group as in the placebo group fulfilled the criteria for "responders" concerning leg pain (71% vs 43 %; P = .03) and for "low residual disease impact" (leg pain VAS < 20 without surgery, 58% vs 30%; P < .05). This group also fared better regarding fewer surgical diskectomies performed (6 vs 13; P = .04).
"The addition of a short course of adalimumab to the treatment regimen of patients suffering from acute and severe sciatica resulted in a small decrease in leg pain and in significantly fewer surgical procedures," the study authors write.
Limitations of this study include inability to determine the sufficient dose and best route of administration for TNF-α inhibitors in radiculopathy because of disk herniation, or to identify subgroups of patients most likely to respond to this treatment.
Future Studies Necessary
"Previous studies have demonstrated that tissue TNF-α levels are increased, in an early phase of the disease, in discal and peridiscal tissue involved in sciatica induced by disc herniation; these and other findings support evidence that TNF-α, IL-1α, IL-1β, IL-6 [interleukin] and prostaglandin E2 are pathophysiologically relevant in the induction of radiculopathy with sciatalgia," Dr. Capria concluded.
"The severity of the nerve damage, with myelin involvement, due both to mechanical and inflammatory mechanisms, should be assessed, demonstrating the occurrence and grade of electrophysiologic changes, as an impaired nerve conduction velocity, demonstrated to be induced by the effects of TNF-α, and the amelioration after administration of TNF-α inhibitors.
Further clinical studies are necessary in patients with a radiculopathy due to disc herniation, to state the adequate dose and the best route of administration of TNF-α inhibitors, elucidating the effective therapeutic role of TNF-α inhibitors in this disease and determining the dosage, times and route of administration, as well as evaluating the possible occurrence of harmful events, as serious infections or adverse cardiovascular events, as seen in patients with rheumatoid arthritis treated with biological drugs."
This study was supported by an unrestricted scientific grant from Abbott. The study authors and Dr. Capria have disclosed no relevant financial relationships.