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.