Peripheral Neuropathy Associated With Proteasome Inhibitors and Immunomodulatory Drugs: A Pharmacovigilance Disproportionality Analysis Using VigiBase

Abstract

Immunomodulatory drugs (IMIDs) and proteasome inhibitors (PIs) are part of the frontline treatment landscape for multiple myeloma (MM). Despite their effectiveness, these drugs are associated with adverse effects, particularly clinically significant drug-induced peripheral neuropathy. The aim of this study was to evaluate the association between peripheral neuropathy and IMIDs and PIs used in MM, stratified by type of nerve dysfunction. VigiBase, the World Health Organization's global database of individual case safety reports (ICSRs), was analyzed. All ICSRs reported from 1 December 2001 to 31 May 2023 were extracted. Peripheral neuropathy cases were identified using MedDRA-preferred terms (neuropathy peripheral, autonomic neuropathy, peripheral motor neuropathy, peripheral sensory neuropathy) and standardized MedDRA queries (SMQ: peripheral neuropathy). Disproportionality signals were assessed using the reporting odds ratio (ROR) and information component (IC). Associations with peripheral neuropathy were found for all IMIDs and PIs. Both IMIDs and PIs were associated with peripheral sensory neuropathy. Associations with autonomic neuropathy were observed for bortezomib (ROR 12.90; 95% CI: 9.01-18.47), ixazomib (ROR 19.01; 95% CI: 7.89-45.80), carfilzomib (ROR 9.35; 95% CI: 3.01-29.10) thalidomide (ROR 8.86; 95% CI: 4.21-18.70). Associations with peripheral motor neuropathy were detected for bortezomib (ROR 63.87; 95% CI: 51.78-78.80), thalidomide (ROR 30.62; 95% CI: 22.67-41.40), lenalidomide (ROR 2.95; 95% CI: 2.11-4.14), pomalidomide (ROR 5.03; 95% CI: 2.91-8.69). Signals of autonomic neuropathy were identified for bortezomib, carfilzomib, ixazomib, and thalidomide, while signals of peripheral motor neuropathy were observed for bortezomib, thalidomide, lenalidomide, and pomalidomide. Associations with peripheral sensory neuropathy were detected for all IMIDs and PIs analyzed.

FIGURE 1

Flowchart of cases/no cases of peripheral neuropathy reported in VigiBase from December 1st, 2001 to May 31st, 2023. Date of extraction: August 21st, 2023.

FIGURE 2

Individual case safety reports for peripheral neuropathy according to MedDRA preferred terms by global region reported in VigiBase, 2001–2023. ICSR, individual case safety report.