Safety and efficacy of Suzetrigine (VX-548) for acute moderate to severe pain in adults; a systematic review and meta-analysis.

INTRODUCTION

Acute moderate to severe pain is a common symptom worldwide and is caused by sudden illness, injury, trauma, burns or post medical/surgical treatments. Current treatment includes multimodal approach with or without opioids depending on the severity of pain but is associated with dependence and tolerance. Suzetrigine, a highly selective voltage-gated sodium channel 1.8 (NaV1.8) inhibitor, is a potential alternate to opioids. This study aimed to evaluate the safety and efficacy of Suzetrigine for acute moderate to severe pain.

METHODS

This study included PubMed, Cochrane Library, and Embase searches till August 2025 for Randomized Controlled Trials (RCTs), evaluating effectiveness of Suzetrigine on adult patients suffering from moderate to severe acute pain. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool (RoB2) and Joanna Briggs Institute checklist (JBI). Primary outcomes were adverse events, and secondary outcomes were Sum of the pain-intensity difference over the 48-h period (SPID48) and Numeric Pain Rating Scale (NPRS) reduction from baseline. Data were analyzed using Revman 5.3. Continuous values were pooled using the standard mean difference (SMD). Dichotomous values were evaluated using risk ratio.

RESULTS

We included 5 RCTs, having 2855 participants. Meta-analysis showed that Suzetrigine exhibits significantly lesser adverse events compared to placebo and Hydrocodon bitartate/ acetamin HB/APAP groups (RR: 0.86; 95% CI: 0.77 to 0.96) and (RR: 0.81; 95% CI: 0.74 to 0.89) respectively. After pooling the data from individual adverse event, we found nausea and dizziness as the most common adverse events in Suzetrigine group when compared to placebo. Suzetrigine was efficacious in reducing SPID48 post-operatively as compared to placebo (SMD: 0.42; 95% CI: 0.31 to 0.53, I2 = 9%). Pooled analysis of SPID48 did not show superiority when compared to HB/APAP.

CONCLUSION

Suzetrigine was better tolerated and more efficacious than placebo making it a promising medication for moderate to severe acute pain treatment in adults.