Association between gabapentinoid exposure and chemotherapy-associated peripheral neuropathy among adults starting new neurotoxic chemotherapy in a multi-hospital health system.

Abstract

e24202 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and dose-limiting toxicity of taxane, platinum, and vinca alkaloid chemotherapy. While duloxetine is recommended for painful CIPN, preventive pharmacologic strategies are limited. Gabapentinoids are frequently used in clinical practice despite minimal evidence of preventive benefit. We evaluated the association between gabapentinoid exposure during chemotherapy and documented drug induced polyneuropathy in a real world cohort. Methods: We conducted a retrospective cohort study using electronic health record data from a multi-hospital health system. Adults receiving neurotoxic chemotherapy (paclitaxel, docetaxel, oxaliplatin, cisplatin, or vincristine) between July 2025 and January 2026 were included. Exposure was defined as receipt of any gabapentin or pregabalin during chemotherapy. The primary outcome was documentation of chemotherapy-associated peripheral neuropathy, defined by ICD-10-CM code G62.0 and/or chemotherapy adverse-effect codes (T45.1X5A, T45.1X5D, T88.7XXS) after chemotherapy initiation. Rates were compared between exposed and unexposed patients and stratified by taxane and platinum regimens. Secondary analyses evaluated G62.0 alone with gabapentinoid exposure. Results: Among 565 patients, the mean age was 66, and 26% were female; 130 (23.0%) had documented neuropathy. Gabapentinoid exposure was present in 182 (32.2%). Neuropathy occurred in 66/182 exposed patients (36.3%) versus 64/383 unexposed patients (16.7%) (RR 2.17, 95% CI 1.60–2.95). Among taxane-treated patients, neuropathy occurred in 49/116 exposed (42.2%) versus 31/200 unexposed (15.5%) (RR 2.72, 95% CI 1.86–3.98). Among platinum-treated patients, neuropathy occurred in 20/65 exposed (30.8%) versus 33/162 unexposed (20.4%) (RR 1.51, 95% CI 0.92–2.48). In secondary analyses limited to G62.0, neuropathy occurred in 64/182 exposed patients (35.2%) versus 59/383 unexposed patients (15.4%) (RR 2.29, 95% CI 1.71–3.07). Conclusions: Gabapentinoid exposure at initiation and or during neurotoxic chemotherapy was associated with higher rates of documented chemotherapy-associated peripheral neuropathy, particularly among taxane-treated patients. Secondary analyses also showed higher neuropathy rates among gabapentinoid-exposed patients. Because the timing of gabapentinoid initiation relative to neuropathy onset cannot be determined, causal inference is limited. Prospective studies are needed to assess preventive or disease-modifying effects. Cohort Gabapentinoid Exposed n/N (%) Unexposed n/N (%) Relative Risk (95% CI) Overall 66 / 182 (36.3%) 64 / 383 (16.7%) 2.17 (1.60–2.95) Taxane-based 49 / 116 (42.2%) 31 / 200 (15.5%) 2.72 (1.86–3.98) Platinum-based 20 / 65 (30.8%) 33 / 162 (20.4%) 1.51 (0.92–2.48)