Understanding the Medical Dictionary for Regulatory Activities (MedDRA) reporting of herpes simplex virus (HSV) adverse events in atopic dermatitis clinical trials.

Abstract

Drug efficacy is best evaluated by randomized, controlled, double-blind clinical trials; however, safety is harder to assess. The Medical Dictionary for Regulatory Activities (MedDRA) is used to track and categorize adverse events (AE) during clinical trials. Recent atopic dermatitis (AD) clinical trials were reviewed to illustrate how an understanding of MedDRA may be helpful when evaluating the rates and nature of adverse events related to herpes simplex virus (HSV) infection. All completed AD clinical trials (excluding phase I studies) with results on clinicaltrials.gov (01/01/2018-01/31/2023) were queried in January 2023. MedDRA version, preferred term (PT) for AEs captured as "HSV", PTs for other AEs possibly related to HSV, frequency thresholds for reporting non-serious AEs, and route of treatment were recorded. Of the 46 clinical trials, 17 had PTs for AEs captured as "HSV". Among all studies, 11 different versions of MedDRA were utilized, from versions 10 to 24.1. In all studies, PTs for AEs captured as "HSV" were listed in the Infections and Infestations system organ class (SOC)classification of MedDRA. PTs varied from "herpes simplex", "herpes virus infection", "herpes ophthalmic", "ophthalmic herpes simplex", "nasal herpes", "oral herpes", "herpes dermatitis", "eczema herpeticum", "genital herpes simplex", and "genital herpes." While one clinical trial of dupilumab (NCT03359356) simply reported the PT "oral herpes" as an AE, a clinical trial of DS107 (NCT03817190) reported the PTs "oral herpes", "herpes simplex", and "herpes virus infection" separately. In the DS107 clinical trial, it is unclear if the same adverse event was reported under multiple PTs or if multiple HSV-related AEs occurred. Although the definition of HSV is unchanged from 2018 to 2023 and there are few changes between MedDRA versions, coding for HSV is complex. HSV events can be reported in different ways, which may impact the interpretation of a drug's safety profile.