OBJECTIVES: Chronic kidney disease (CKD)-associated pruritus is linked with numerous clinical and patient-reported outcomes. Pregabalin is indicated for neuropathic pain, and also used off-label to reduce pruritus symptoms. There are, however, concerns about adverse events, namely altered mental status and falls. We explored real-world pregabalin utilization patterns and relevant adverse events in US hemodialysis patients, and how they may differ by diagnosis of CKD-associated pruritus vs. neuropathic pain.

METHODS: We used claims data from 533,232 adult hemodialysis patients in the USRDS database between 2016-2020 with Fee-For-Service Medicare Part D coverage. Pregabalin use, dose, and time to discontinuation were stratified by time-updated diagnosis of CKD-associated pruritus or neuropathic pain. The associations between time-varying pregabalin dose – defined as current prescription updated continuously – and six adverse events were analysed by recurrent event Andersen-Gill model and adjusted for potential confounders, separately by time-updated diagnosis of CKD-associated pruritus or neuropathic pain.

RESULTS: Point-prevalence of pregabalin prescription was 2.4% overall, and was higher among patients with neuropathic pain (4.0%) than with CKD-associated pruritus (1.7%). Median [IQR] time to discontinuation was 4.6 [1.5, 12.6] months in the neuropathic pain group and 4.5 [1.0, 12.0] months in the CKD-associated pruritus group. Mean pregabalin dose was higher (132 vs. 115 mg/day) in the neuropathic pain vs. CKD-associated pruritus group.

Adverse event rates ranged from 9.2 (fracture) to 37.7 (altered mental status) per 100 patient-years. We observed a dose-response association between pregabalin dose and adverse events in patients with neuropathic pain and CKD-associated pruritus.

CONCLUSIONS: Use of pregabalin in hemodialysis patients was associated with a higher risk of adverse events vs. no use (including altered mental status, dizziness, falls, and fracture), even at doses as low as 25 mg/day. Prescribers should consider the clinically relevant side effects of pregabalin when providing treatment options to their patients with neuropathic pain or CKD-associated pruritus.