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.