Universität zu Köln

Szepanowski, Fabian, Warnke, Clemens, zu Hoerste, Gerd Meyer, Mausberg, Anne K., Hartung, Hans-Peter, Kleinschnitz, Christoph and Stettner, Mark (2021). Secondary Immunodeficiency and Risk of Infection Following Immune Therapies in Neurology. CNS Drugs, 35 (11). S. 1173 - 1189. NORTHCOTE: ADIS INT LTD. ISSN 1179-1934

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Abstract

Secondary immunodeficiencies (SIDs) are acquired conditions that may occur as sequelae of immune therapy. In recent years a number of disease-modifying therapies (DMTs) has been approved for multiple sclerosis and related disorders such as neuromyelitis optica spectrum disorders, some of which are frequently also used in- or off-label to treat conditions such as chronic inflammatory demyelinating polyneuropathy (CIDP), myasthenia gravis, myositis, and encephalitis. In this review, we focus on currently available immune therapeutics in neurology to explore their specific modes of action that might contribute to SID, with particular emphasis on their potential to induce secondary antibody deficiency. Considering evidence from clinical trials as well as long-term observational studies related to the patients' immune status and risks of severe infections, we delineate long-term anti-CD20 therapy, with the greatest data availability for rituximab, as a major risk factor for the development of SID, particularly through secondary antibody deficiency. Alemtuzumab and cladribine have relevant effects on circulating B-cell counts; however, evidence for SID mediated by antibody deficiency appears limited and urgently warrants further systematic evaluation. To date, there has been no evidence suggesting that treatment with fingolimod, dimethyl fumarate, or natalizumab leads to antibody deficiency. Risk factors predisposing to development of SID include duration of therapy, increasing age, and pre-existing low immunoglobulin (Ig) levels. Prevention strategies of SID comprise awareness of risk factors, individualized treatment protocols, and vaccination concepts. Immune supplementation employing Ig replacement therapy might reduce morbidity and mortality associated with SIDs in neurological conditions. In light of the broad range of existing and emerging therapies, the potential for SID warrants urgent consideration among neurologists and other healthcare professionals.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Szepanowski, Fabian UNSPECIFIED UNSPECIFIED UNSPECIFIED Warnke, Clemens UNSPECIFIED UNSPECIFIED UNSPECIFIED zu Hoerste, Gerd Meyer UNSPECIFIED UNSPECIFIED UNSPECIFIED Mausberg, Anne K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartung, Hans-Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Kleinschnitz, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Stettner, Mark UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-594702
DOI:	10.1007/s40263-021-00863-4
Journal or Publication Title:	CNS Drugs
Volume:	35
Number:	11
Page Range:	S. 1173 - 1189
Date:	2021
Publisher:	ADIS INT LTD
Place of Publication:	NORTHCOTE
ISSN:	1179-1934
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHRONIC LYMPHOCYTIC-LEUKEMIA; PLACEBO-CONTROLLED TRIAL; RELAPSING MULTIPLE-SCLEROSIS; ZOSTER-VIRUS INFECTIONS; B-CELL DEPLETION; DIMETHYL FUMARATE; INTRAVENOUS IMMUNOGLOBULIN; ALEMTUZUMAB TREATMENT; INTERFERON BETA-1A; CONTROLLED PHASE-3 Multiple languages Clinical Neurology; Pharmacology & Pharmacy; Psychiatry Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59470