The Efficacy of Nerve Growth Factor Antibody for the Treatment of Osteoarthritis Pain and Chronic Low-Back Pain: A Meta-Analysis

Abstract

Background: Nerve growth factor (NGF) plays a crucial role in pain modulation and is being considered as a new therapeutic target for pain therapy. The purpose of this metaanalysis was to study the efficacy of anti-NGF antibodies for the treatment of osteoarthritis pain and chronic low-back pain, and to provide evidence and direction for further research and practice. Methods: PubMed, Embase, Wanfang Data, and China National Knowledge Infrastructure (CNKI) were searched from inception to November 30, 2019. Eligible studies should include randomized clinical trial-based investigations of anti-NGF antibody treatment for osteoarthritis pain and chronic low-back pain. Pooled overall mean changes from baseline to check point in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) measures of pain, physical function, and Patient's Global Assessment (PGA) were calculated with either a fixed-effects model or a randomeffects model, depending on the tests for heterogeneity. Sensitivity analysis and bias of publication were assessed. Results: A total of seven studies (3890 patients) were included in this meta-analysis. The pooled analysis showed a statistically significant reduction in the WOMAC pain (standardized mean difference (SMD) =-2.22, 95% confidence interval (CI) =-3.44 to-0.99, Z =-3.55, P = 0.0004; I 2 = 99%), the WOMAC Physical Function (SMD =-2.76, 95% CI =-4.22 to-1.30, Z =-3.71, P = 0.0002; I 2 = 99%), and the PGA Index (SMD =-2.76, 95% CI =-4.42 to-1.09, Z =-3.24, P = 0.0012; I 2 = 99%). Pooled differences of adverse events rates in experimental and control groups was 0.11 (95% CI = 0.02 to 0.20, Z = 2.41, P = 0.016; I 2 = 83%). Conclusion: Our meta-analysis data indicate that anti-NGF antibodies can relieve pain and improve function in patients with osteoarthritis pain and chronic low-back pain.

Commentary: The Efficacy of Nerve Growth Factor Antibody for the Treatment of Osteoarthritis Pain and Chronic Low-Back Pain: A Meta-analysis

“…The recent article by Yang et al (2020) is timely. Nerve growth factor (NGF) inhibitors may have benefits for chronic pain, and the U. S. Food and Drug Administration has recently accepted regulatory submission of tanezumab (an anti-NGF agent) for osteoarthritis.…”

“…The Efficacy of Nerve Growth Factor Antibody for the Treatment of Osteoarthritis Pain and Chronic Low-Back Pain: A Meta-analysis by Yang, S., Huang, Y., Ye, Z., Li, L. and Zhang, Y. (2020).…”

“…First, Yang et al (2020) have missed several osteoarthritis trials that were eligible for inclusion in their review, for example, Schnitzer et al (2015), Brown et al (2013), andBrown et al (2012). These trials are indexed in both Embase and PubMed (two of the databases searched by Yang et al (2020)) and meet all inclusion criteria for the review.…”

“…First, Yang et al (2020) have missed several osteoarthritis trials that were eligible for inclusion in their review, for example, Schnitzer et al (2015), Brown et al (2013), andBrown et al (2012). These trials are indexed in both Embase and PubMed (two of the databases searched by Yang et al (2020)) and meet all inclusion criteria for the review. Brown et al (2013) and Brown et al (2012) are also found in the reference list of one of the included trials (Kivitz et al, 2013) indicating that Yang et al (2020) failed to include these studies since they stated in the review that "The references of the articles included were also searched in case of any additional studies not previously identified in the initial literature search.…”

Of mice and men: converging on a common molecular understanding of osteoarthritis

“…Several biological drugs targeting NGF, all delivered systemically (intravenously or subcutaneously), have been tested in phase 2 studies, with a meta-analysis showing efficacy across the different studies. 135 Two companies have now published phase 2–3 studies using NGF neutralising antibodies, 136 , 137 , 138 with fasinumab and tanezumab showing efficacy over placebo. Concerns over patients developing rapidly progressive osteoarthritis in index and non-index joints (ranging from 2 to 10% according to dose and study) forced the FDA to introduce mitigation strategies, which included reducing highest doses and prohibiting the use of concomitant non-steroidal anti-inflammatory drugs.…”