Herpes Zoster Infections With Multiple Sclerosis Disease-Modifying Therapies: A Real-World Pharmacovigilance Study

Abstract

Background and objectives: Immunosuppressive multiple sclerosis (MS) disease-modifying therapies (DMTs) may increase the risk of opportunistic infections such as herpes zoster (HZ). We sought to evaluate the risk of HZ across various MS DMTs using publicly available pharmacovigilance reporting data.

Methods: We queried the Food and Drug Administration Adverse Event Reporting System (FAERS) and OpenVigil 2.1 for reports of HZ involving immunosuppressive MS DMTs (ocrelizumab [OCR], ofatumumab [OFT], rituximab [RTX], natalizumab [NTZ], alemtuzumab, dimethyl fumarate and diroximel fumarate [DRF], fingolimod [FING], siponimod [SIP], ozanimod [OZ], mitoxantrone [MITO], cladribine [CLAD], and teriflunomide [TERF]) and calculated reporting odds ratios and their 95% CIs.

Results: We identified 4,210 total reports of HZ across these MS DMTs. All had disproportionally higher RORs compared with all other FAERS medications. Alemtuzumab had the greatest reporting risk (ROR; 95% CI) (11.1; 9.7-12.6), followed by OCR (9.3; 8.6-10.0), FING (5.6; 5.2-6.0), CLAD (5.3; 3.7-4.2), NTZ (4.0; 3.7-4.2), RTX (3.8; 3.5-4.1), SIP (3.2; 2.4-4.2), DRF (3.1; 2.4-4.1), OFT (3.0; 2.6-3.6), dimethyl fumarate (2.5; 2.3-2.8), OZ (2.5; 1.8-3.6), MITO (2.4; 1.6-3.6), and TERF (1.6; 1.3-1.9).

Discussion: Immunosuppressive MS DMTs are associated with greater HZ reporting in the FAERS. These findings emphasize the importance of pre-DMT HZ vaccination because of avoidable HZ infections.