Suzetrigine (a NaV1.8 inhibitor) versus placebo for acute postoperative pain: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND

NaV1.8 channels, expressed in peripheral nociceptors, mediate sustained pain signaling. Their inhibition offers a potential opioid-sparing strategy for postoperative pain, although efficacy and safety remain incompletely defined. We synthesized randomized evidence for suzetrigine versus placebo in postoperative pain.

METHODS

We conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant meta-analysis of randomized controlled trials comparing suzetrigine (a NaV1.8 inhibitor) versus placebo in surgical patients. The primary outcome was 24-hour pain with the Numeric Pain Rating Scale; secondary outcomes included 48-hour pain, change-from-baseline, and adverse events. Risk of bias was assessed with the Cochrane Risk of Bias 2 tool, and for analyses, we used Hartung-Knapp models with heterogeneity and prediction intervals reported. Random-effects models used Hartung-Knapp adjustments (2-sided α = 0.05).

RESULTS

We included 4 randomized datasets across 2 phase 3 publications (n = 1584; 1009 intervention, 575 placebo). The mean participant age was 44.9 years; 92.3% were women. Procedures included abdominoplasty (n = 823) and bunionectomy (n = 761). Suzetrigine significantly reduced pain at 24 hours (mean difference = -0.93; 95% confidence interval [CI], -1.38 to -0.48; I2 = 66.0%) and 48 hours (mean difference = -1.02; 95% CI, -1.32 to -0.72; I2 = 11.8%). Analyses of change-from-baseline confirmed consistent benefit. Subgroup analyses revealed similar effects across surgery types. A lower incidence of nausea (risk ratio = 0.63; 95% CI, 0.42-0.95) and dizziness (risk ratio = 0.57; 95% CI, 0.34-0.96) was observed in the suzetrigine group, with no significant differences in headache, vomiting, or constipation. Meta-regressions showed no moderation by sample size or publication year. Risk of bias was low in 2 studies and raised "some concerns" in 2.

CONCLUSION

Suzetrigine produced modest reductions in pain at 24 to 48 hours versus placebo. Because opioid consumption was not consistently reported, no conclusions can be drawn regarding opioid-sparing.