Efficacy and Safety of Anti-nerve Growth Factor Monoclonal Antibodies in Managing Chronic Musculoskeletal Pain: A Systematic Review with Network Meta-analysis.

BACKGROUND

Anti-nerve growth factor (NGF) monoclonal antibodies (mAbs) have emerged as a promising new class of analgesics, offering potential benefits in managing particular painful musculoskeletal (MSK) conditions. However, their long-term safety remains uncertain, leading to regulatory non-approval of these agents. This study aims to evaluate the efficacy and safety of individual anti-NGF mAbs compared to other analgesics when treating chronic MSK pain.

METHODS

Our literature search included PubMed, Scopus, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov through April 25th, 2025. Articles eligible for inclusion were randomized controlled trials (RCTs) comparing one of the human anti-NGF mAbs to other interventions in adults with chronic MSK pain. Primary outcomes evaluated were changes from baseline in pain, physical function, and patient global assessment (PGA) scores, as well as risks of adjudicated arthropathies (AAs) and abnormal peripheral sensation (APS). We used the Cochrane Risk of Bias 2 (RoB-2) tool to assess risk of bias. Pairwise and network meta-analyses were performed using random-effects models. Treatments were ranked using the cumulative ranking curve (SUCRA), and a multi-criteria decision analysis with Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) was applied to integrate all efficacy and safety outcomes. Statistical analyses were conducted in R (v4.3.1) using the meta, netmeta, gemtc, and Multi-Criteria Decision Aiding (MCDA) packages.

RESULTS

A total of 29 studies, involving 27,747 patients with osteoarthritis or chronic low back pain, were included in this analysis. Compared to placebo, fasinumab showed the highest improvements in pain (standardized mean difference [SMD] - 0.40, 95% CI [- 0.52, - 0.29], p < 0.001) and physical function (SMD - 0.42, 95% CI [- 0.53, - 0.31], p < 0.001), followed by tanezumab (pain: SMD - 0.36, 95% CI [- 0.44, - 0.28], p < 0.001; function: SMD - 0.39, 95% CI [- 0.47, - 0.31], p < 0.001). For safety, both fasinumab and tanezumab demonstrated a significant risk for AAs (risk ratio [RR] 4.7, 95% CI [3.61, 6.13], p < 0.001; and RR 3.84, 95% CI [2.07, 7.14], p < 0.001, respectively) and APS (RR 1.99, 95% CI [1.49, 2.65], p < 0.001; and RR 2.46, 95% CI [1.93, 3.14], p < 0.001, respectively) relative to placebo. While fulranumab was less effective (pain: SMD - 0.25, 95% CI [- 0.42, - 0.07], p < 0.01; function: SMD - 0.25, 95% CI [- 0.43, - 0.07], p < 0.01), it showed better overall safety against placebo relative to both agents, demonstrating a significant risk only for APS events (RR 1.78, 95% CI [1.09, 2.92], p < 0.05).

CONCLUSIONS

Anti-NGF mAbs, particularly fasinumab and tanezumab, are associated with the greatest levels of pain relief and functional improvement over placebo within this analysis. However, these benefits are counterbalanced by significant risks of joint-related adverse events. Implementation of strict safety protocols is essential when considering these agents for further evaluation.

PROTOCOL REGISTRATION: PROSPERO ID: CRD420251104612.