JMIR Publications

ABSTRACT

Background:

Low back pain (LBP) is the leading cause of years lived with disability worldwide. Most people with LBP receive the diagnosis of non-specific LBP or sciatica. Medications are commonly prescribed but have limited analgesic effects and are associated with adverse events. A novel treatment approach is to target neurotrophins such as nerve growth factor (NGF) to reduce pain intensity. NGF-inhibitors have been tested in some randomised controlled trials in recent years. These medicines show promise for the treatment of chronic LBP, but their efficacy and safety need to be evaluated to guide regulatory actions.

Objective:

To evaluate the analgesic effects and safety of medicines targeting neurotrophins in the treatment of LBP.

Methods:

In this systematic review, we will include published and unpublished records of parallel randomised controlled trials (RCTs) and the first phase of cross-over RCTs that compare the effects of medicines targeting neurotrophins with any control group. We will search CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, the EU Clinical Trials Register and the WHO International Clinical Registry Platform from inception. Pairs of authors will independently screen the records for eligibility, and we will independently extract data in duplicate. We will conduct a quantitative synthesis (meta-analysis) with the studies that report data sufficiently and compared the medicines of interest versus placebo. We will use random-effects models and calculate estimates of effects and heterogeneity for each outcome. We will assess the risk of bias for each study using the Cochrane Collaboration’s tool, and form judgements of confidence in the evidence according to GRADE recommendations. We will use the PRISMA statement to report the findings. We plan to conduct a subgroup analysis by condition, type of medication and timepoint. We will assess the impact of a potential new trial on an existing meta-analysis. Data from studies that meet inclusion criteria but cannot be meta-analysed will be reported narratively.

Results:

The protocol was registered on the Open Science Framework on 19 May 2020. As of August 2020, we have identified 1818 records.

Conclusions:

This systematic review with meta-analysis will provide evidence for the efficacy and safety of NGF-inhibitors for reducing pain in non-specific LBP and sciatica. The inclusion of new studies and unpublished data may improve the precision of the effect estimates and guide regulatory actions of the medications for LBP and sciatica. Clinical Trial: Registration: Open Science Framework (osf.io/b8adn)