CYP2D6-GUIDED OPIOID PRESCRIBING AND CLINICAL OUTCOMES IN CHRONIC PAIN: EVIDENCE FROM THE ADOPT PGX TRIAL LINKED TO MEDICARE AND MEDICAID CLAIMS
Author(s)
Suk-Chan Jang, PharmD, PhD1, Jungjun Bae, MS1, Rachel Myers, PhD2, Larisa Cavallari, PharmD1, Elizabeth Harris, BS2, Julie Johnson, PharmD3, Josh Peterson, MD, MPH4, Todd Skaar, PhD5, Paul Richard Dexter, MD6, Simona Volpi, PhD7, Renee Rider, MS, JD, CGC7, Hrishikesh Chakraborty, DrPH2, Erica Elwood, MHA1, Haesuk Park, PhD1;
1University of Florida, Gainesville, FL, USA, 2Duke University, Durham, NC, USA, 3The Ohio State University, Columbus, OH, USA, 4Vanderbilt University Medical Center, Nashville, TN, USA, 5Indiana University School of Medicine, Indianapolis, IN, USA, 6Indiana University, Indianapolis, IN, USA, 7National Human Genome Research Institute, Bethesda, MD, USA
1University of Florida, Gainesville, FL, USA, 2Duke University, Durham, NC, USA, 3The Ohio State University, Columbus, OH, USA, 4Vanderbilt University Medical Center, Nashville, TN, USA, 5Indiana University School of Medicine, Indianapolis, IN, USA, 6Indiana University, Indianapolis, IN, USA, 7National Human Genome Research Institute, Bethesda, MD, USA
OBJECTIVES: Pharmacogenetic guidelines recommend avoiding certain opioids in individuals with absent or reduced CYP2D6 activity, as genetic variation or concomitant use of CYP2D6 inhibitors can alter opioid metabolism and lead to inadequate pain control. While CYP2D6-guided opioid prescribing may optimize chronic pain management, the clinical impact of prolonged pharmacogenetic (PGx) non-concordance remains unclear. We assessed associations between prolonged PGx non-concordance, pain severity, and the risk of emergency department (ED) visits or hospitalization.
METHODS: Participants in A Depression and Opioid Pragmatic Trial in Pharmacogenetics (ADOPT PGx; NCT05966129) with ≥3 months of chronic pain who used or were considered for tramadol, codeine, hydrocodone, or oxycodone were linked to their Medicare/Medicaid claims. Patient-reported pain scores (higher scores indicate worse pain) were obtained from the trial, and healthcare utilization from claims. For this study, PGx non-concordance was defined as ≥30 days of opioid therapy discordant with CYP2D6 phenotype (activity score ≤0.75 or >2). Generalized estimating equations modeled repeated pain scores, and logistic regression estimated odds ratios (ORs) for all-cause ED visits and hospitalization, adjusting for demographics.
RESULTS: Among 349 participants (mean age 62 years; 72% female; 39% Black), 237 were PGx concordant, and 112 were non-concordant. Mean pain score did not differ meaningfully between non-concordant and concordant groups (month 3: 10.41 vs 10.11; month 6: 10.09 vs 9.79). However, pain scores tended to be higher with longer duration of non-concordance, although this association was not statistically significant (coefficient 0.162, p=0.56). Compared with concordant participants, non-concordant participants had higher odds of ED visit (25.9 % vs. 23.2%; OR 1.25, 95% CI 0.73-2.14) and hospitalization (7.1% vs 4.6%; OR 1.55, 95% CI 0.57-4.07), though these were not statistically significant.
CONCLUSIONS: Prolonged PGx non-concordance may be associated with modest differences in pain scores and all-cause healthcare utilization. Further studies examining non-opioid pain medications and pain-related healthcare utilization are warranted.
METHODS: Participants in A Depression and Opioid Pragmatic Trial in Pharmacogenetics (ADOPT PGx; NCT05966129) with ≥3 months of chronic pain who used or were considered for tramadol, codeine, hydrocodone, or oxycodone were linked to their Medicare/Medicaid claims. Patient-reported pain scores (higher scores indicate worse pain) were obtained from the trial, and healthcare utilization from claims. For this study, PGx non-concordance was defined as ≥30 days of opioid therapy discordant with CYP2D6 phenotype (activity score ≤0.75 or >2). Generalized estimating equations modeled repeated pain scores, and logistic regression estimated odds ratios (ORs) for all-cause ED visits and hospitalization, adjusting for demographics.
RESULTS: Among 349 participants (mean age 62 years; 72% female; 39% Black), 237 were PGx concordant, and 112 were non-concordant. Mean pain score did not differ meaningfully between non-concordant and concordant groups (month 3: 10.41 vs 10.11; month 6: 10.09 vs 9.79). However, pain scores tended to be higher with longer duration of non-concordance, although this association was not statistically significant (coefficient 0.162, p=0.56). Compared with concordant participants, non-concordant participants had higher odds of ED visit (25.9 % vs. 23.2%; OR 1.25, 95% CI 0.73-2.14) and hospitalization (7.1% vs 4.6%; OR 1.55, 95% CI 0.57-4.07), though these were not statistically significant.
CONCLUSIONS: Prolonged PGx non-concordance may be associated with modest differences in pain scores and all-cause healthcare utilization. Further studies examining non-opioid pain medications and pain-related healthcare utilization are warranted.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
CO157
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
SDC: Systemic Disorders/Conditions (Anesthesia, Auto-Immune Disorders (n.e.c.), Hematological Disorders (non-oncologic), Pain)