The Difference Between Pregabalin and Gabapentin in the Risk of Fragility Fractures - A Nationwide High-dimensional Propensity Score Matched Cohort Study

Background: Pregabalin and gabapentin are considered as first-line treatment for neuropathic pain. Initiation of both pregabalin and gabapentin has been associated with an increased risk of fragility fractures. Due to increasing use of both gabapentin and pregabalin and the small differences in the pharmacokinetic properties of the two gabapentinoids, we wanted to assess whether a difference in the risk of fragility fractures exists.

Objectives: The aim of this study was to assess whether the initiation of gabapentin compared with initiation of pregabalin was associated with a different risk of fragility fractures.

Methods: We performed a new user, high-dimensional propensity score matched active comparator cohort study with the use of the nationwide health registers in Denmark. The included patients were aged ≥ 18 years who initiated either pregabalin or gabapentin for any indication in the period from 1 January 1996 until 31 December 2018. Individuals meeting the inclusion criteria were followed from the first filled prescription until a fragility fracture, emigration, death, or until 90 days of follow-up. We applied a high-dimensional propensity score approach to match new users of gabapentin with new users of pregabalin in a 1:1 intention-to-treat approach. Hazard ratios (HR) were estimated with the use of Cox proportional hazard regression, and incidence rate difference (IRD) were obtained.

Results: We identified 305,086 eligible patients, 73,865 initiated pregabalin and 231,221 initiating gabapentin. After trimming and matching we included 48,265 matched pairs for further analysis. The mean age for the two matched cohorts was 56 (IQR 44-69) years and the average follow-up was approximately 11,500 person years in each matched cohort. The incidence rates (IR) of fragility fractures were 22.9 (95%CI 20.3-25.8), and 23.3 (95%CI 20.7-26.3) per 1,000 person years (PY) for pregabalin and gabapentin-exposed patients, respectively. This yielded a HR of 1.02 (95%CI 0.86-1.21) when using gabapentin as the intervention-drug, and pregabalin as the reference-drug. The IRD was estimated to 0.4 (95%CI -3.5-4.4).

Conclusions: The risk of fragility fractures among patients initiating gabapentin was not different compared to those initiating pregabalin.