Cutaneous adverse events in multiple sclerosis patients treated with daclizumab

Irene Cortese; Joan Ohayon; Kaylan Fenton; Chyi-Chia Lee; Mark Raffeld; Edward W Cowen; John J DiGiovanna; Bibiana Bielekova

doi:10.1212/WNL.0000000000002417

Cutaneous adverse events in multiple sclerosis patients treated with daclizumab

Neurology. 2016 Mar 1;86(9):847-55. doi: 10.1212/WNL.0000000000002417. Epub 2016 Feb 3.

Authors

Irene Cortese¹, Joan Ohayon¹, Kaylan Fenton¹, Chyi-Chia Lee¹, Mark Raffeld¹, Edward W Cowen¹, John J DiGiovanna¹, Bibiana Bielekova²

Affiliations

¹ From the Neuroimmunology Clinic (I.C., J.O.) and the Neuroimmunological Diseases Unit (B.B.), National Institute of Neurological Disorders and Stroke, and the Laboratory of Pathology (C.-C.L., M.R.) and the Dermatology Branch (E.W.C., J.J.D.), Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda; and Department of Neurology (K.F.), Johns Hopkins School of Medicine, Baltimore, MD.
² From the Neuroimmunology Clinic (I.C., J.O.) and the Neuroimmunological Diseases Unit (B.B.), National Institute of Neurological Disorders and Stroke, and the Laboratory of Pathology (C.-C.L., M.R.) and the Dermatology Branch (E.W.C., J.J.D.), Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda; and Department of Neurology (K.F.), Johns Hopkins School of Medicine, Baltimore, MD. bibi.bielekova@nih.gov.

Abstract

Objective: To analyze the spectrum and mechanisms of cutaneous adverse events (AEs) in patients with multiple sclerosis treated with daclizumab high-yield process (DAC-HYP).

Methods: A total of 31 participants in an institutional review board-approved open-label phase I study of DAC-HYP (NCT01143441) were prospectively evaluated over 42 months for development of cutaneous AEs. Participants provided written informed consent. Fifteen participants were naive to anti-CD25 therapy (cohort B), while 16 had received daclizumab (Zenapax; Hoffmann-La Roche) IV for 4-9 years (mean 5.8 years) prior to enrollment (cohort A). Immunohistochemistry was performed on pretreatment and posttreatment skin biopsies of normal-appearing skin (cohort B only) and on lesional biopsies in participants presenting with rash (both cohorts).

Results: Cutaneous AEs occurred in 77% of patients, the majority presenting with patches of eczema requiring no treatment. Moderate to severe rash developed in 6 participants (19%) and required discontinuation of DAC-HYP in 4 (13%). More severe rashes presented psoriasiform phenotype, but lesional biopsies lacked features of either psoriasis or drug hypersensitivity eruptions. Instead, irrespective of clinical severity, lesional biopsies showed nonspecific features of eczematous dermatitis, but with prominent CD56+ lymphocytic infiltrates. Pretreatment and posttreatment biopsies of normal-appearing skin demonstrated no histopathologic changes.

Conclusions: Observed cutaneous AEs are likely related to the immunomodulatory effects DAC-HYP exerts on innate lymphoid cells, including natural killer cells. Vigilance and timely management of skin reactions may prevent treatment discontinuation in participants with severe rash.

Publication types

Clinical Trial, Phase I
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antibodies, Monoclonal, Humanized / adverse effects*
Antibodies, Monoclonal, Humanized / therapeutic use*
Daclizumab
Drug Eruptions / diagnosis*
Drug Eruptions / etiology*
Female
Humans
Immunoglobulin G / adverse effects*
Immunoglobulin G / therapeutic use*
Immunosuppressive Agents / adverse effects
Immunosuppressive Agents / therapeutic use
Male
Multiple Sclerosis / complications*
Multiple Sclerosis / drug therapy*
Treatment Outcome

Substances

Antibodies, Monoclonal, Humanized
Immunoglobulin G
Immunosuppressive Agents
Daclizumab

Grants and funding

Intramural NIH HHS/United States