Animal experiments and clinical studies have revealed that TNF- inhibitors can prevent the decline of nucleus pulposus-induced neural transmission speed and neural damage and thus have a protective effect on neurodegeneration , , . 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- inhibitors could reduce the risk ratio (RR) of discectomy or radicular block (combined endpoint; RR?=?0.51, 95% CI 0.26 to 1 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 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- inhibitors showed limited clinical Amsacrine hydrochloride value in the treatment of sciatica caused by herniated discs and/or spinal stenosis. Introduction Disk herniation-induced sciatica is one of the most common causes of lower back and leg pain among young adults. Previous studies have demonstrated that the outcomes of conservative treatment, such as medication and physical therapy, are similar to the natural course of this disease . Although epidural steroid injections can relieve a portion of patients pain, they cannot restore the patients physical function . Recently, some scholars have stated that non-opioid analgesic agents, discectomy and epidural steroid injection are effective ; however, the opposing opinion indicates that discectomy is only effective for acute neurodynia, and its long-term outcome is not superior to that of conservative treatment . In addition, because of nerve root adhesions or epidural adhesions, epidural steroid injection cannot relieve pain in a considerable number of patients . Tumor necrosis factor-alpha (TNF-) is an inflammatory factor involved in the pathophysiological mechanism underlying disk herniation-induced sciatica , . In the past Amsacrine hydrochloride decade, some scholars have attempted to use TNF- Amsacrine hydrochloride inhibitors to treat sciatica. Previous non-randomized controlled trials have shown that this type of agent has potential efficacy and IKBKB antibody a relatively high patient tolerance , . However, afterwards, various randomized controlled trials (RCTs) demonstrated that these agents yielded inconsistent outcomes. A newly published systematic review and meta-analysis revealed that the evidence supporting the use of TNF- inhibitors to treat sciatica is inadequate . Nevertheless, this study has some limitations: (1) four high-quality RCTs C were missed; (2) among all of the enrolled trials, a visual analogue scale (VAS) score range of 0 to 100 was adopted in a portion of trials C, while a score range of 0 to 10 was applied in others C. The authors used a weighted mean difference (WMD) technique to pool all of the data together; however, this is not a standard and conventional method commonly used in meta-analysis ; and (3) in addition, we disagree that the authors method of pooling together all of Amsacrine hydrochloride the data regarding the outcomes of discectomy, including the data obtained during short-term, medium-term and long-term follow-ups. The primary purpose of this study was to evaluate the treatment value of TNF- inhibitors compared with placebos and steroids in terms of five endpoints at short-term follow-up (3 months), medium-term follow-up (3 to 12 months) and long-term follow-up (12 months). The five endpoints that were adopted were the Oswestry Disability Index, VAS pain intensity in the leg, VAS pain intensity in the lower back, global perceived effect (satisfaction) or return to work (combined endpoint), and discectomy or radicular block (combined endpoint). The secondary purpose was to evaluate the patient tolerance of the adverse reaction of TNF- inhibitors. Methods Using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)  as a guideline, we conducted this systematic review and meta-analysis. The present study Amsacrine hydrochloride is a complement to and update of the study performed by Williams et al. ..