Genotype–guided opioid prescribing could change postoperative opioid selection but may not affect postoperative pain intensity or opioid use compared with usual care, according to a recent randomized clinical trial.
In the multicenter pragmatic trial, researchers found that patients receiving genotype-guided prescribing had higher concordance between prescribed opioids and metabolic phenotype but experienced similar pain intensity and opioid use compared with patients receiving usual postoperative pain management.
Trial Evaluated Genotype-Guided Pain Management
The researchers conducted an open-label randomized clinical trial across eight US health systems to evaluate whether CYP2D6-guided opioid prescribing affected postoperative pain and opioid use.
They enrolled 1,602 patients scheduled for surgery expected to cause postoperative pain lasting 7 to 10 days between March 2021 and September 2023. Patients with chronic opioid use were excluded.
Among the enrolled participants, 351 patients with an actionable cytochrome P450 2D6 phenotype—classified as poor metabolizers or intermediate metabolizers—completed surgery and were randomly assigned to genotype-guided opioid prescribing (n = 176) or usual care (n = 175).
The participants had a mean age of 62 years and 68% of them identified as female. The most common procedures were total knee arthroplasty (50%) and total hip arthroplasty (28%).
In the intervention group, patients underwent CYP2D6 genotyping prior to surgery. Prescribers received recommendations to avoid tramadol, hydrocodone, and codeine in poor or intermediate metabolizers while maintaining autonomy over prescribing decisions.
The primary outcome was the Silverman Integrated Analgesic Assessment score at 10 days postsurgery, a rank-based composite measure combining average pain intensity on a 10-point scale and prescribed opioid use expressed as morphine milligram equivalents—with higher scores indicating greater pain and opioid use.
Genotype Guidance Changed Prescribing Patterns
Genotype-informed prescribing substantially increased concordance between opioid selection and metabolic phenotype.
Concordance occurred in 64% of the patients in the genotype-guided arm compared with 27% of those in the control arm.
The intervention also shifted the types of opioids prescribed. Hydrocodone prescribing occurred in 24% of the patients in the genotype-guided group vs 58% in the control group.
Hydromorphone prescribing was more common in the genotype-guided arm, occurring in 39% of patients compared with 3% of control participants.
Nearly all of the patients in both groups were prescribed an opioid postoperatively.
Pain and Opioid Use Similar Between Groups
Despite the prescribing differences, postoperative pain outcomes were similar between the groups.
At 10 days following surgery:
- Mean Silverman Integrated Analgesic Assessment score was 1.4 in the genotype-guided group vs −1.4 in the control group.
- Mean numeric pain rating was 5.2 vs 5.1.
- Mean opioid use was 13.7 vs 13.2 morphine milligram equivalents per day.
None of these outcomes differed between the study arms.
The secondary outcomes were also similar. These included composite pain intensity, mobility at 30 days, and overall well-being at 1 month following surgery.
Among the participants prescribed opioids, 13% (n = 41) reported not taking any opioid medication within 10 days following surgery.
Multimodal Analgesia Common
Use of nonopioid pain management strategies was frequent across both groups.
Among the participants with actionable phenotypes:
- 55% received a nerve block
- 65% reported acetaminophen use
- 46% reported nonsteroidal anti-inflammatory drug use
- 34% reported gabapentinoid use.
These therapies were similarly distributed between the treatment groups.
The researchers noted that multimodal pain management strategies are recommended to reduce postoperative pain and minimize opioid use.
Subgroup Analyses Showed Similar Findings
Subgroup analyses showed no statistically significant differences between the study arms. In the per-protocol population, the mean 10-day Silverman Integrated Analgesic Assessment score was 0.2 in the genotype-guided arm and −1.4 in the control arm. The results were also similar when analyses were limited to patients undergoing knee or hip arthroplasty and when patients receiving oxycodone were excluded.
Study Limitations
The researchers noted several study limitations. The pragmatic trial design allowed prescribers to retain autonomy over opioid prescribing, resulting in less-than-complete adherence to genotype-based recommendations. The Silverman Integrated Analgesic Assessment score also showed large variability, which may have reduced the ability to detect differences between groups. In addition, missing data for the primary outcome occurred in about 11% of the actionable population.
Conclusion
The genotype-guided approach significantly changed opioid prescribing but didn't improve postoperative pain outcomes.
“[A] CYP2D6-guided approach led to significant changes in postsurgical opioid prescribing but had no effect on pain control or opioid use,” wrote lead study author Larisa H. Cavallari, PharmD, of the Department of Pharmacotherapy and Translational Research as well as the Center for Pharmacogenomics and Precision Medicine at the College of Pharmacy at the University of Florida, and colleagues.
They concluded that the findings “do not support a role for CYP2D6-guided opioid therapy in the contemporary postoperative setting of multimodal pain management.”
Co–study author Chancellor F. Gray, MD, disclosed receiving personal fees from Smith & Nephew unrelated to the present study. Co–study author Josh F. Peterson, MD, reported personal fees from Myome outside the submitted work. Co–study author Aniwaa Owusu Obeng, PharmD, reported serving as an advisor for Datum outside the submitted work. Co–study author Lori A. Orlando, MD, reported grant support from Duke University during the study. The study authors reported no other conflicts of interest.
Source: JAMA Network Open