BACKGROUND AND OBJECTIVE: Currently, no satisfactory treatment is available for sciatica caused by herniated discs and/or spinal stenosis. The objective of this study is to assess the value of tumor necrosis factor (TNF)-α inhibitors in the treatment of sciatica.
METHODS: Without language restrictions, we searched PubMed, OVID, EMBASE, the Web of Science, the Clinical Trials Registers, the Cochrane Central Register of Controlled Trials and the China Academic Library and Information System. We then performed a systematic review and meta-analysis on the enrolled trials that met the inclusion criteria.
RESULTS: Nine prospective randomized controlled trials (RCTs) and two before-after controlled trials involving 531 patients met our inclusion criteria and were included in this study. Our systematic assessment and meta-analysis demonstrated that in terms of the natural course of the disease, compared with the control condition, TNF-α inhibitors neither significantly relieved lower back and leg pain (both p > 0.05) nor enhanced the proportion of patients who felt overall satisfaction (global perceived effect (satisfaction)) or were able to return to work (return to work) (combined endpoint; p > 0.05) at the short-term, medium-term and long-term follow-ups. In addition, compared with the control condition, TNF-α inhibitors could reduce the risk ratio (RR) of discectomy or radicular block (combined endpoint; RR = 0.51, 95% CI 0.26 to 1.00, p = 0.049) at medium-term follow-up, but did not decrease RR at the short-term (RR = 0.64, 95% CI 0.17 to 2.40, p = 0.508) and long-term follow-ups (RR = 0.64, 95% CI 0.40 to 1.03, p = 0.065).
CONCLUSION: The currently available evidence demonstrated that other than reducing the RR of discectomy or radicular block (combined endpoint) at medium-term follow-up, TNF-α inhibitors showed limited clinical value in the treatment of sciatica caused by herniated discs and/or spinal stenosis.
BACKGROUND: Low back pain, with or without radiculopathy, is an important cause of disability and economic expenditure. However, many patients are not achieving optimal pain control with existing medications. Tumor necrosis factor antagonists (anti-TNFα) could be an alternative drug treatment.
OBJECTIVES: Systematic review the efficacy and safety of anti-TNFα in the treatment of low back pain with or without radiculopathy.
STUDY DESIGN: Inclusion criteria were observational studies with safety as an outcome, and randomized or nonrandomized controlled trial (RCT) studies on efficacy and/or safety of anti-TNFα drugs on low back pain. Exclusion criteria included patients with auto-immune conditions or osteoporosis.
RESULTS: Studies were assessed independently by 2 authors regarding inclusion/exclusion criteria, risk of bias, clinical relevance, quality, and strength of evidence (GRADE approach). Of the 1,179 studies retrieved, all duplicates were excluded and then the inclusion/exclusion criteria was applied. One observational study (n = 143) and 11 RCTs remained (n = 539): 8 for etanercept (n = 304), one for adalimumab (n = 61), one for adalimumab and etanercept (n = 60), one for infliximab (n = 40) and one for REN-1654 (n = 74). Only 3 etanercept and 2 adalimumab studies showed statistically significant pain relief when compared to placebo. There was no difference in the overall incidence of adverse effects when comparing anti-TNF-α and placebo.
LIMITATIONS: Despite the statistically significant effect, this meta-analysis has important limitations, such as high heterogeneity and high use of outcome imputation.
CONCLUSIONS: There is low evidence that epidural etanercept has a low-to-moderate effect size when compared to placebo for pain due to discogenic lumbar radiculopathy (5 studies, n=185), with a standardized mean difference = -0.43 (95% confidence interval [CI] -0.84 to -0.02).There is moderate evidence that epidural etanercept does not have a higher adverse effects incidence rate when compared to placebo for discogenic lumbar radiculopathy (5 studies, n = 185) with a relative risk (RR) = 0.84 (95% CI 0.53 to 1.34).There is moderate evidence that anti-TNFα does not have a higher adverse effects incidence rate when compared to placebo for low back pain (10 studies, n= 343) with an RR = 0.93 (95% CI 0.56 to 1.55).We strongly suggest that anti-TNFα continue to be studied in experimental settings for the treatment of low back pain. We cannot currently recommend this therapy in clinical practice. New research could shed some light on the efficacy of anti-TNFα and change this recommendation in the future.
Journal»European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society
PURPOSE: Systematic review comparing biological agents, targeting tumour necrosis factor α, for sciatica with placebo and alternative interventions.
METHODS: We searched 21 electronic databases and bibliographies of included studies. We included randomised controlled trials (RCTs), non-RCTs and controlled observational studies of adults who had sciatica treated by biological agents compared with placebo or alternative interventions.
RESULTS: We pooled the results of six studies (five RCTs and one non-RCT) in meta-analyses. Compared with placebo biological agents had: better global effects in the short-term odds ratio (OR) 2.0 (95 % CI 0.7-6.0), medium-term OR 2.7 (95 % CI 1.0-7.1) and long-term OR 2.3 [95 % CI 0.5 to 9.7); improved leg pain intensity in the short-term weighted mean difference (WMD) -13.6 (95 % CI -26.8 to -0.4), medium-term WMD -7.0 (95 % CI -15.4 to 1.5), but not long-term WMD 0.2 (95 % CI -20.3 to 20.8); improved Oswestry Disability Index (ODI) in the short-term WMD -5.2 (95 % CI -14.1 to 3.7), medium-term WMD -8.2 (95 % CI -14.4 to -2.0), and long-term WMD -5.0 (95 % CI -11.8 to 1.8). There was heterogeneity in the leg pain intensity and ODI results and improvements were no longer statistically significant when studies were restricted to RCTs. There was a reduction in the need for discectomy, which was not statistically significant, and no difference in the number of adverse effects.
CONCLUSIONS: There was insufficient evidence to recommend these agents when treating sciatica, but sufficient evidence to suggest that larger RCTs are needed.
Currently, no satisfactory treatment is available for sciatica caused by herniated discs and/or spinal stenosis. The objective of this study is to assess the value of tumor necrosis factor (TNF)-α inhibitors in the treatment of sciatica.
METHODS:
Without language restrictions, we searched PubMed, OVID, EMBASE, the Web of Science, the Clinical Trials Registers, the Cochrane Central Register of Controlled Trials and the China Academic Library and Information System. We then performed a systematic review and meta-analysis on the enrolled trials that met the inclusion criteria.
RESULTS:
Nine prospective randomized controlled trials (RCTs) and two before-after controlled trials involving 531 patients met our inclusion criteria and were included in this study. Our systematic assessment and meta-analysis demonstrated that in terms of the natural course of the disease, compared with the control condition, TNF-α inhibitors neither significantly relieved lower back and leg pain (both p > 0.05) nor enhanced the proportion of patients who felt overall satisfaction (global perceived effect (satisfaction)) or were able to return to work (return to work) (combined endpoint; p > 0.05) at the short-term, medium-term and long-term follow-ups. In addition, compared with the control condition, TNF-α inhibitors could reduce the risk ratio (RR) of discectomy or radicular block (combined endpoint; RR = 0.51, 95% CI 0.26 to 1.00, p = 0.049) at medium-term follow-up, but did not decrease RR at the short-term (RR = 0.64, 95% CI 0.17 to 2.40, p = 0.508) and long-term follow-ups (RR = 0.64, 95% CI 0.40 to 1.03, p = 0.065).
CONCLUSION:
The currently available evidence demonstrated that other than reducing the RR of discectomy or radicular block (combined endpoint) at medium-term follow-up, TNF-α inhibitors showed limited clinical value in the treatment of sciatica caused by herniated discs and/or spinal stenosis.
