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Peripheral neuropathies after BRAF and/or MEK inhibitor treatment: A pharmacovigilance study

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Reports suggested the potential occurrence of peripheral neuropathies (PN) in patients treated with BRAF (BRAFi) and/or MEK inhibitors (MEKi) for BRAF‐activated tumours. We aimed to better characterize these PN. We… Click to show full abstract

Reports suggested the potential occurrence of peripheral neuropathies (PN) in patients treated with BRAF (BRAFi) and/or MEK inhibitors (MEKi) for BRAF‐activated tumours. We aimed to better characterize these PN. We queried the French pharmacovigilance database for all cases of PN attributed to BRAFi and/or MEKi. Fifteen patients were identified. Two main clinical PN phenotypes were seen. Six patients presented a length‐dependent, axonal polyneuropathy: symptoms were mostly sensory and affecting the lower limbs; management and outcome were variable. Nine patients developed a demyelinating polyradiculoneuropathy: symptoms affected the four limbs and included hypoesthesia, weakness and ataxia; cranial nerves were involved in four cases; most patients received intravenous immunoglobulins or glucocorticoids, with variable outcome; one patient was rechallenged with a different BRAFi/MEKi combination with a rapid relapse in symptoms. In conclusion, patients under BRAFi/MEKi therapy may develop treatment‐induced PN. Two main phenotypes can occur: a symmetric, axonal, length‐dependent polyneuropathy and a demyelinating polyradiculoneuropathy.

Keywords: braf mek; brafi meki; treatment; neuropathies braf; pharmacovigilance; peripheral neuropathies

Journal Title: British Journal of Clinical Pharmacology
Year Published: 2022

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