Rui V Duarte, Sue Copley, Alan Batterham, Neil Hall, Eric Buchser, Sam Eldabe
ITDD is associated with meaningful reductions in pain from baseline, and functional and HRQoL improvement in patients with chronic non-cancer pain. However, the certainty of evidence is low for pain and very low for other outcomes due to study limitations. Improved reporting and controlled trials are needed to strengthen the evidence base, with careful consideration of a control intervention that maintains clinical equipoise.
BACKGROUND/IMPORTANCE: Intrathecal drug delivery (ITDD) is an established intervention for chronic non-cancer pain, cancer pain, and spasticity. However, ITDD is not routinely commissioned for non-cancer pain in some countries, including England. A comprehensive synthesis of its clinical impact and safety profile in this population is lacking.
OBJECTIVE: To investigate the clinical outcomes and adverse events (AEs) associated with ITDD in adults with chronic non-cancer pain.
EVIDENCE REVIEW: A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and a registered protocol (CRD42024581505). Searches across MEDLINE, EMBASE, CENTRAL, and WikiStim until September 2024 were performed to identify studies reporting pain intensity, function, health-related quality of life (HRQoL), and AEs in ITDD recipients with non-cancer pain. Risk of bias was assessed using National Institutes of Health and Cochrane tools. A random-effects meta-analysis was performed on the pain intensity outcome (0-10 scale equivalent) at the 12-month time point.
FINDINGS: 39 studies (n=2652) were included; 20 single-arm comparisons contributed to meta-analysis. The pooled mean reduction in pain from baseline was 2.64 (95% CI 2.19 to 3.08). Accounting for between-study heterogeneity in effect size, the 95% prediction interval is 0.734 to 4.54 units. The probability that the change from baseline in a new, similar study would be greater than the minimum clinically important difference of 2 units is 75% (95% CI 68% to 83%). All studies reported improvements from baseline in function and HRQoL. Reporting of AEs or discontinuation of ITDD due to AEs was inconsistent. Risk of bias was moderate or high for cohort studies and pre-post studies, low for two crossover randomized trials and one parallel-arm randomized trial, and high for one parallel-arm randomized trial.
CONCLUSIONS: ITDD is associated with meaningful reductions in pain from baseline, and functional and HRQoL improvement in patients with chronic non-cancer pain. However, the certainty of evidence is low for pain and very low for other outcomes due to study limitations. Improved reporting and controlled trials are needed to strengthen the evidence base, with careful consideration of a control intervention that maintains clinical equipoise.