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. 2023 May;98(5):676-688.
doi: 10.1016/j.mayocp.2022.11.004. Epub 2023 Apr 5.

Baclofen and the Risk of Encephalopathy: A Real-World, Active-Comparator Cohort Study

Y Joseph Hwang  1 , Alex R Chang  2 , Daniel J Brotman  3 , Lesley A Inker  4 , Morgan E Grams  5 , Jung-Im Shin  6
Affiliations

Baclofen and the Risk of Encephalopathy: A Real-World, Active-Comparator Cohort Study

Y Joseph Hwang et al. Mayo Clin Proc. 2023 May.

Abstract

Objective: To quantify the risk of encephalopathy associated with oral baclofen compared with other muscle relaxants-tizanidine or cyclobenzaprine.

Patients and methods: We conducted a new-user, active-comparator study of 2 pairwise cohorts using tertiary health system data from Geisinger Health in Pennsylvania (January 1, 2005, through December 31, 2018). Adults (aged ≥18 years) newly treated with baclofen or tizanidine were included in cohort 1. Adults newly treated with baclofen or cyclobenzaprine were included in cohort 2. Propensity score-based inverse probability of treatment weighting (IPTW) was used to balance the respective cohorts on 45 patient characteristics. Fine-Gray competing risk regression was used to estimate the risk of encephalopathy.

Results: Cohort 1 included 16,192 new baclofen users and 9782 new tizanidine users. The 30-day risk of encephalopathy was higher in patients treated with baclofen vs tizanidine (IPTW incidence rate, 64.7 vs 28.3 per 1000 person-years) with an IPTW subdistribution hazard ratio (SHR) of 2.29 (95% CI, 1.43 to 3.67). This risk persisted through 1 year (SHR, 1.32 [95% CI, 1.07 to 1.64]). Similarly in cohort 2, baclofen vs cyclobenzaprine was associated with a greater risk of encephalopathy at 30 days (SHR, 2.35 [95% CI, 1.59 to 3.48]) that persisted through the first year of treatment (SHR, 1.94 [95% CI, 1.56 to 2.40]).

Conclusion: The risk of encephalopathy was greater with baclofen vs tizanidine or cyclobenzaprine use. The elevated risk was apparent as early as 30 days and persisted through the first year of treatment. Our findings from routine care settings may inform shared treatment decisions between patients and prescribers.

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Conflict of interest statement

Dr. Hwang reports grants from Division of Hospital Medicine at Johns Hopkins Hospital, Department of Medicine, Johns Hopkins University, during the conduct of the study. Dr. Chang reports grants from Novo Nordisk, personal fees from Novartis, outside the submitted work. Dr. Brotman has nothing to disclose. Dr. Inker has nothing to disclose. Dr. Grams reports grants from NIDDK, during the conduct of the study; serving on the scientific advisory board for NKF and USRDS, outside the submitted work; serving on the executive committee for KDIGO, outside the submitted work. Dr. Shin reports grants from NIH, during the conduct of the study; grants from Merck, outside the submitted work.

Figures

Figure 1.
Figure 1.
Cumulative incidence of encephalopathy in the weighted study population in (A) Cohort 1 (baclofen vs tizanidine) and (B) Cohort 2 (baclofen vs cyclobenzaprine). Abbreviations: IPTW, inverse probability of treatment weighting
Figure 1.
Figure 1.
Cumulative incidence of encephalopathy in the weighted study population in (A) Cohort 1 (baclofen vs tizanidine) and (B) Cohort 2 (baclofen vs cyclobenzaprine). Abbreviations: IPTW, inverse probability of treatment weighting
Figure 2.
Figure 2.
1-year risk of encephalopathy in subgroups of age, estimated glomerular filtration rate, sex, and concomitant opioid use in (A) Cohort 1 (baclofen vs tizanidine) and (B) Cohort 2 (baclofen vs cyclobenzaprine). Abbreviations: CI, confidence interval; eGFR, estimated glomerular filtration rate; IPTW, inverse probability of treatment weighting; SHR, subdistribution hazard ratio
Figure 2.
Figure 2.
1-year risk of encephalopathy in subgroups of age, estimated glomerular filtration rate, sex, and concomitant opioid use in (A) Cohort 1 (baclofen vs tizanidine) and (B) Cohort 2 (baclofen vs cyclobenzaprine). Abbreviations: CI, confidence interval; eGFR, estimated glomerular filtration rate; IPTW, inverse probability of treatment weighting; SHR, subdistribution hazard ratio
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