741: SUZETRIGINE VS OPIOID ANALGESICS AND POSTOPERATIVE OUTCOMES: A REAL WORLD PROPENSITY-MATCHED COHORT

Topic: Clinical Science
Subtopic: Pain category (ICD-11), Acute postsurgical pain, Pharmacological treatments, Pain in Special Populations , Treatment/management

Background and Aims: Perioperative pain management modality potentially influences psychiatric morbidity and healthcare utilization. The opioids have been most commonly used for managing postoperative pain and carry a high degree of risk for creating mood disorders, anxiety, sleep disturbances, and healthcare burdens. A novel non-opioid analgesic, Suzetrigine, may be able to effectively manage postoperative pain without some of the psychological and economic risks that come from the use of opioids. In this study, we measured psychiatric outcomes and emergency department (ED) usage among postoperative patients who received either suzetrigine or opioids.

Methods: This retrospective cohort study using the TriNetX US Collaborative Network, encompassing 64 organizations. Adult patients (> Age 18 years) underwent surgery and received suzetrigine were compared with patients who underwent surgery and received opioids. Propensity score matching (1:1) performed matching cohorts based on demographics (age, gender, racial/ethnic status), social determinants of health (ICD-10 Z55-Z65), family histories of substance abuse and psychiatric disorders (Z81.x), measures of prior healthcare utilization, and pre-existing clinical severity using Elixhauser-Charlson comorbidity proxies (hypertensive diseases [I10-I15], diabetes mellitus [E08-E13], ischemic heart disease [I22-I25], and chronic pulmonary disease [J42-J47]). Matching also included behavioral risk factors (tobacco use and physical inactivity) and body mass index (BMI). Following matching, there were 2,221 patients in each cohort. The primary outcome assessed within one year after surgery was ED utilization, depression, anxiety, post-traumatic stress disorder (PTSD) and sleep disorders. Risk estimates and survival analyses were used to compare the outcomes.

Results: In propensity-matched analyses, suzetrigine use was associated with a reduction in multiple psychiatric outcomes and healthcare utilization compared to opioid analgesics. There was less ED utilization in the suzetrigine cohort (5.9% v 13.1%, RR 0.45, p< .001). The psychiatric outcomes were also lower in the suzetrigine cohort than the opioid cohort, including depression (3.1% v 4.7%, RR 0.65, p= .005), anxiety (4.7% v 7.2%, RR 0.65, p< .001), PTSD (0.5% v 1.4%, RR 0.36, p= .002), and sleep disorders (4.2% v 6.0%, RR 0.71, p= .008). The survival analysis suggested an earlier onset of psychiatric diagnosis among the opioid recipients.

Conclusions: In a matched real-world cohort of surgical patients, suzetrigine use was associated with lower short-term rates of selected postoperative outcomes compared with opioid analgesics.

References: Bertoch, T. (2025). Suzetrigine, a Nonopioid NaV1.8 Inhibitor for Treatment of Moderate-to-Severe Acute Pain: Two Phase 3 Randomized Clinical Trials. Anesthesiology. https://doi.org/10.1097/ALN.0000000000005460
Bertoch, T., D’Aunno, D., McCoun, J., Solanki, D., Taber, L., Urban, J., Oswald, J., Swisher, M. W., Tian, S., Miao, X., Correll, D. J., Negulescu, P., Bozic, C., & Weiner, S. G. (2025). Suzetrigine, a Nonopioid Na V 1.8 Inhibitor for Treatment of Moderate-to-severe Acute Pain: Two Phase 3 Randomized Clinical Trials. Anesthesiology, 142(6), 1085–1099. https://doi.org/10.1097/ALN.0000000000005460
Brummett, C. M., Evans-Shields, J., England, C., Kong, A. M., Lew, C. R., Henriques, C., Zimmerman, N. M., & Sun, E. C. (2021). Increased health care costs associated with new persistent opioid use after major surgery in opioid-naive patients. Journal of Managed Care & Specialty Pharmacy, 27(6), 760–771. https://doi.org/10.18553/jmcp.2021.20507
Courtney, D. (2025). Suzetrigine: A novel selective sodium channel inhibitor for pain. American Journal of Health-System Pharmacy. https://doi.org/10.1093/ajhp/zxaf219
Edwards, D. A., Hedrick, T. L., Jayaram, J., Argoff, C., Gulur, P., Holubar, S. D., Gan, T. J., Mythen, M. G., Miller, T. E., Shaw, A. D., Thacker, J. K. M., McEvoy, M. D., & POQI-4 Working Group. (2019). American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Perioperative Management of Patients on Preoperative Opioid Therapy. Anesthesia and Analgesia, 129(2), 553–566. https://doi.org/10.1213/ANE.0000000000004018
Gupta, S., Sharma, S., & Kumar, A. (2026). Opioid Sparing Multimodal Analgesia in Enhanced Recovery After Surgery Protocols A comprehensive Review. 04(01). (World). https://doi.org/10.5281/zenodo.18491097
Ho, D., Imai, K., King, G., & Stuart, E. A. (2011). MatchIt: Nonparametric Preprocessing for Parametric Causal Inference. Journal of Statistical Software, 42, 1–28. https://doi.org/10.18637/jss.v042.i08

Presenting Author: Anjali Pathak, MD
Submitting Author: Anjali Pathak

Senior Author: Dr Rishab Gupta, MD

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Abhinav Singh Verma: MD - Case western reserve University/ MetroHealth