Background

In 2019, alcohol use disorder (AUD) affected 14.5 million people aged 12 years or over, but only 4% of patients receive Food and Drug Administration (FDA) approved medication for AUD. Challenges in treating AUD include limited physician knowledge and experience in prescribing, prescription complexity, and a perception that treatment is only available through specialty clinics. While Acamprosate requires taking 6 large pills daily, Gabapentinoids are simple to use and commonly prescribed by primary care physicians. This study aimed to examine the association of Gabapentinoids and Acamprosate with the progression of alcoholic liver disease (ALD) among patients with AUD.

Methods

Using the Veterans Health Administration Corporate Data Warehouse (CDW), we extracted data of patients who had an inpatient or outpatient diagnosis of AUD using International Classification of Diseases (ICD) codes. We then identified patients who were initiated on either Acamprosate or Gabapentinoids after being diagnosed with AUD. We excluded patients with decompensated liver cirrhosis and liver transplant. The primary outcome was a composite outcome of ALD progression (compensated cirrhosis, decompensated cirrhosis, alcoholic hepatitis, ALD, Hepatocellular Carcinoma) as defined by ICD codes. We formed a propensity score (PS) from 85 variables encompassing demographics, comorbidities, liver and kidney function tests, vital signs, healthcare utilization, and medication use. We propensity score-matched treatment groups. We created another PS-matched cohort restricted to patients who continued their medications for 120 days or more (persistent cohort).

Results

Out of 29,707 Acamprosate users and 440,495 Gabapentinoids users, we matched 24,477 pairs. The composite outcome of ALD progression occurred in 15.78% of acamprosate users and 13.37% of Gabapentinoids users (odds ratio [OR]: 1.21; 95% confidence interval [95%CI]: 1.15-1.28). Compensated cirrhosis developed in 8.31% of Acamprosate users and 7.36% of Gabapentinoids users (OR: 1.14, 95%CI: 1.07-1.22). Decompensated cirrhosis developed in 5.05% of Acamprosate users and 3.96% of Gabapentinoids users (OR: 1.29, 95%CI: 1.18-1.41). On secondary analysis in patients with pre-existing liver disease, the composite outcome occurred in 30.41% of Acamprosate users and 25.82% of the Gabapentinoids group (OR: 1.15, 95%CI: 1.10-1.21). Similar outcomes were observed in the PS-matched persistent cohort of 12,258 pairs.

Conclusion

Although Acamprosate has been approved for the treatment of AUD, Gabapentinoids have been used off-label for the same purpose. Our study indicates that Gabapentinoids were associated with slower progression of ALD than Acamprosate. The outcomes also favored the Gabapentinoids group in the persistent cohort. Hence, Gabapentinoids may be a valuable option for the treatment of AUD.

Richard Henriquez

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