Anti-Nerve Growth Factor in the Treatment of
Low Back Pain and Radiculopathy: A Systematic
Review and a Meta-Analysis
Authors: Amadera Joao E D 
Published: February 2021

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 antiNGF 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.
Key Words: back pain, anti-ngf, spine, sciatica, nerve growth factor, radiculopathy, treatment