Comparative Effectiveness, Safety, and Costs of Gabapentinoids in Older Adults With Long‐Term Opioid Use
Kevin T. Pritchard, Chun‐Ting Yang, Qiaoxi Chen, James M. Wilkins, Dae Hyun Kim, Kueiyu Joshua LinABSTRACT
Background
It is unclear whether managing chronic pain with adjuvant gabapentin versus pregabalin can safely reduce long‐term opioid use among older adults. Our objective was to compare clinical effectiveness, safety, and costs of initiating gabapentin versus pregabalin.
Methods
We conducted a retrospective cohort study and target trial emulation in a US National sample of 2013–2018 Medicare fee‐for‐service and 2004–2024 Optum's de‐identified Clinformatics Data Mart Database (Optum CDM). Participants included cancer‐free adults aged ≥ 65 with long‐term opioid use (> 90 days) who newly initiated gabapentin or pregabalin. New initiators of gabapentin were matched 1:1 to pregabalin initiators using propensity scores and 91 baseline covariates. The primary exposure was new dispensing (without use in the preceding 6 months) of gabapentin versus pregabalin. The primary outcome was opioid discontinuation, defined by a 60‐day refill gap. Safety outcomes included mortality and hospitalization. Hazard ratio (HR) estimates were calculated over 365‐days. Database‐specific estimates were pooled using inverse‐variance weighting. Pharmacy‐specific and non‐pharmacy costs were measured as annualized insurer expenses. Cost differences were estimated separately by database.
Results
We included 12,415 matched pairs (Mean age [SD] = 73 [7] years, women = 64%, White = 73%). Relative to pregabalin, gabapentin was not associated with discontinuing opioids (HR [95% CI], 0.97 [0.93–1.02]), mortality (HR [95% CI], 0.91 [0.75–1.10]), or hospitalization (HR [95% CI], 0.95 [0.90–1.00]). Comparatively, gabapentin had lower pharmacy‐specific costs in Medicare (Mean $‐1657 [$‐2298 to $‐1016]) and Optum CDM population ($‐888 [$‐1238 to $‐539]); non‐pharmacy costs were similar (Medicare: Mean $170 [$‐1027 to $1367]; Optum CDM: Mean $‐883 [$‐3309 to $1543]).
Conclusions
Compared to pregabalin, gabapentin treatment was not associated with opioid discontinuation, hospitalization, or mortality in the pooled analysis. Gabapentin had lower pharmacy‐related costs than pregabalin in Medicare and Optum CDM. Findings may not generalize to younger or uninsured populations. Residual confounding is possible as administrative claims data lack pain severity measures.