Comparative Clinical Effectiveness of Analgesics for the Treatment of Moderate-to-Severe Acute Pain: A Systematic Review and Network Meta-Analysis
Author(s)
Dmitriy Nikitin, MSPH, Sol Sanchez, BA, Finn R. Raymond, BS, Abigail Wright, PhD, MSc, David M Rind, MD, MSc;
Institute for Clinical and Economic Review, Boston, MA, USA
Institute for Clinical and Economic Review, Boston, MA, USA
OBJECTIVES: To evaluate the relative clinical effectiveness of opioid analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), and a first-in-class Nav1.8 inhibitor, suzetrigine, to each another and to placebo for the treatment of moderate-to-severe acute pain.
METHODS: We systematically identified and reviewed randomized controlled trials (RCTs) of opioid analgesics, NSAIDs, and suzetrigine in adults with moderate-to-severe acute pain following bunionectomy and abdominoplasty procedures. We conducted a random-effects Bayesian network meta-analysis (NMA) for the outcome of the time-weighted sum of pain-intensity difference over a 48-hour period (SPID48); NMA inputs consisted of the standardized mean difference (SMD) between active treatment and placebo in SPID48. The analysis included 16 therapies grouped into four analgesic classes: opioids (separated into high-dose and low-dose categories, with hydrocodone 5 mg/acetaminophen 325 mg classified as low-dose), NSAIDs, and suzetrigine. Uncertainties surrounding surgical procedures and risk of bias were explored in sensitivity analyses.
RESULTS: We identified 16 relevant RCTs that met our inclusion criteria. Treatment with each pooled analgesic class produced a statistically significant reduction in pain intensity versus placebo as calculated by the SMD of SPID48 results: high-dose opioids had the greatest effect size (SMD: 0.5; 95% Credible Interval [CrI]: 0.35 to 0.65), followed by suzetrigine (0.43; 95% CrI: 0.28 to 0.57), low-dose opioids (0.41; 95% CrI: 0.26 to 0.53), and NSAIDs (0.34; 95% CrI: 0.19 to 0.49). There were no statistically significant differences between any active treatment classes. The results of the NMA were robust to sensitivity analyses, which included a bunionectomy-only study population, and an exclusion of studies deemed to be high-risk per the Cochrane Risk of Bias 2 Assessment Tool.
CONCLUSIONS: While all analgesic classes effectively reduced pain intensity compared to placebo, comparative data on safety, tolerability, and addiction potential remains insufficient for comprehensive treatment decision-making in acute pain management.
METHODS: We systematically identified and reviewed randomized controlled trials (RCTs) of opioid analgesics, NSAIDs, and suzetrigine in adults with moderate-to-severe acute pain following bunionectomy and abdominoplasty procedures. We conducted a random-effects Bayesian network meta-analysis (NMA) for the outcome of the time-weighted sum of pain-intensity difference over a 48-hour period (SPID48); NMA inputs consisted of the standardized mean difference (SMD) between active treatment and placebo in SPID48. The analysis included 16 therapies grouped into four analgesic classes: opioids (separated into high-dose and low-dose categories, with hydrocodone 5 mg/acetaminophen 325 mg classified as low-dose), NSAIDs, and suzetrigine. Uncertainties surrounding surgical procedures and risk of bias were explored in sensitivity analyses.
RESULTS: We identified 16 relevant RCTs that met our inclusion criteria. Treatment with each pooled analgesic class produced a statistically significant reduction in pain intensity versus placebo as calculated by the SMD of SPID48 results: high-dose opioids had the greatest effect size (SMD: 0.5; 95% Credible Interval [CrI]: 0.35 to 0.65), followed by suzetrigine (0.43; 95% CrI: 0.28 to 0.57), low-dose opioids (0.41; 95% CrI: 0.26 to 0.53), and NSAIDs (0.34; 95% CrI: 0.19 to 0.49). There were no statistically significant differences between any active treatment classes. The results of the NMA were robust to sensitivity analyses, which included a bunionectomy-only study population, and an exclusion of studies deemed to be high-risk per the Cochrane Risk of Bias 2 Assessment Tool.
CONCLUSIONS: While all analgesic classes effectively reduced pain intensity compared to placebo, comparative data on safety, tolerability, and addiction potential remains insufficient for comprehensive treatment decision-making in acute pain management.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
CO57
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
SDC: Injury & Trauma