Immediate and acute adverse effects following transforaminal epidural steroid injections with dexamethasone.

BACKGROUND: Transforaminal epidural steroid injections (TFESI) are widely used for the conservative treatment of radicular pain. The use of dexamethasone in TFESIs is relatively new; therefore, immediate and acute adverse effects that it may cause are not fully updated. OBJECTIVE: To evaluate immediate and acute adverse effects following TFESI with dexamethasone. STUDY DESIGN: Prospective, observational study. SETTING: A spine center affiliated with a rehabilitation hospital. METHODS: One hundred fifty consecutive patients receiving TFESI for the management of radicular and axial spinal pain at the cervical, lumbar, and sacral levels with dexamethasone using fluoroscopic guidance with digital subtraction technology were enrolled. The occurrence of adverse effects in patients in the 2-week time period following interventions was monitored through a set of questionnaires followed up by phone calls scheduled for 1 day, day 3, and day 14. Intensity and duration of side effects were recorded. RESULTS: Of the 150 patients enrolled, 31 patients (19.5%) experienced adverse effects within the first 30 minutes following the intervention. The most common adverse effects were numbness and tingling in the limb, which developed in 19 patients (11.95%) followed by perineal pruritus that occurred in 7 cases (4.4%). Patients also reported experiencing adverse effects within the 3 days following intervention; most complained of headaches, insomnia, hiccups, flushing, and increased radicular pain. No major complications were noted. LIMITATIONS: The sample size enrolled might be too small to perceive possible rare side effects related to the procedure. The 2-week follow-up period is a limitation for evaluating late side effects. CONCLUSIONS: This study offers provision to interventionalists that TFESI with dexamethasone when performed by experienced hands and with proper technique has minor self-limited transient adverse effects that can be easily managed. Patients should be made aware of these adverse effects and their management. Further larger studies are needed to validate the safe use of dexamethasone and the safety of transforaminal epidural injections.

Anti-nerve growth factor in the treatment of low back pain and radiculopathy: a systematic review and a meta-analysis.

BACKGROUND: Low back pain with or without radiculopathy is an important cause of disability and economic expenditure. However, many patients are not meeting optimal pain control through existing treatments. Recent studies have linked nerve growth factor (NGF) and the pathophysiology of persistent pain. Anti-NGF could be an alternative drug treatment for low back pain. OBJECTIVE: Systematically review the efficacy and safety of anti-NGF in the treatment of low back pain. METHODS: A systematic review of the literature with no language, date or publication status restriction, using Medline, EMBASE, Cochrane Library, and the clinicaltrials.gov database. Additional literature was retrieved by conferring with experts in the field or reviewing bibliographies and annals of meetings and congresses. Search terms included "monoclonal antibodies," "nerve growth factor," "anti-ngf," "fulranumab," "tanezumab," "sciatica," "back pain," and "spine." STUDY DESIGN: Inclusion criteria were observational studies with safety as an outcome and randomized or nonrandomized controlled trials studying the efficacy and/or the safety of anti-NGF drugs on low back pain. Exclusion criteria included patients with autoimmune conditions or osteoporosis. Studies were assessed independently by 2 authors regarding inclusion/exclusion criteria, risk of bias, clinical relevance, and quality of evidence (GRADE approach). RESULTS: 1,168 studies were retrieved. After excluding duplicates and applying the inclusion/exclusion criteria, 4 RCTs remained (n = 2,109): 2 for tanezumab, one for REGN475, and one for fulranumab. Only the tanezumab studies showed any significant difference over placebo (n = 1,563) for both pain relief and functional improvement. CONCLUSIONS: There is very low evidence that systemically administered anti-NGF therapy has a small positive effect compared to placebo for both pain relief (standarized mean difference [SMD] = -0.29, 95% confidence interval [CI] -0.58 to 0.00) and functional improvement (SMD = -0.21, 95%CI -0.37 to -0.05 ) of low back pain. There was low evidence of adverse effects (AEs) compared to placebo and low evidence of neurological AEs than placebo (relative risk = 1.93, 95%CI 1.41 to 2.64).Tanezumab, as a specific anti-NGF treatment, showed low evidence of a small to moderate effect for pain relief of low back pain (SMD = -0.44, 95%CI -0.81 to -0.07); and low evidence of a small effect for functional improvement (SMD = -0.26, 95%CI -0.40 to -0.12) with systemic administration, although not clinically significant. Tanezumab and anti-NGFs overall had, respectively, moderate and low evidence of overall AEs and serious AEs and a higher risk of developing neurological AEs when compared with placebo. Although anti-NGF, specifically tanezumab, showed a low-to-moderate effect on pain relief and functional improvement, it cannot be recommended for low back pain treatment. Without more research on the pathophysiology of anti-NGFs and adverse effects, its use is not safe in the overall population. However, as corroborated by the US Food and Drug Administration, this meta-analysis underscores a role for greater insight into anti-NGF therapy for painful conditions that are refractory to current drugs, such as oncologic pain, chronic pancreatitis, and phantom-limb pain. Given the pathophysiology of axial pain involving inflammatory mediators and the adverse effects of systemic anti-NGF use, consideration of local therapies may warrant further exploration.

Anti-tumor necrosis factor antagonists in the treatment of low back pain and radiculopathy: a systematic review and meta-analysis.

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.