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.

• MeSH
• Alemtuzumab administration & dosage   adverse effects   MeSH
• Dimethyl Fumarate administration & dosage   adverse effects   MeSH
• Fingolimod Hydrochloride administration & dosage   adverse effects   MeSH
• Immunoglobulin G blood   immunology   MeSH
• Immunologic Factors administration & dosage   adverse effects   MeSH
• Immunosuppressive Agents administration & dosage   adverse effects   MeSH
• Immunotherapy adverse effects   MeSH
• Infections blood   chemically induced   immunology   MeSH
• Coinfection MeSH
• Humans MeSH
• Natalizumab administration & dosage   adverse effects   MeSH
• Neurology methods   trends   MeSH
• Rituximab administration & dosage   adverse effects   MeSH
• Risk Factors MeSH
• Age Factors MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Alemtuzumab MeSH
• Dimethyl Fumarate MeSH
• Fingolimod Hydrochloride MeSH
• Immunoglobulin G MeSH
• Immunologic Factors MeSH
• Immunosuppressive Agents MeSH
• Natalizumab MeSH
• Rituximab MeSH

We report the final analysis of the PROLONG study on ofatumumab maintenance in relapsed chronic lymphocytic leukemia (CLL). In all, 480 patients with CLL in complete or partial remission after second- or third-line treatment were randomized 1:1 to ofatumumab (300 mg first week, followed by 1000 mg every 8 weeks for up to 2 years) or observation. Median follow-up duration was 40.9 months. Median progression-free survival was 34.2 and 16.9 months for ofatumumab and observation arms, respectively, (hazard ratio, 0.55 [95% confidence interval, 0.43-0.70]; P < 0.0001). Median time to next treatment for ofatumumab and observation arms, respectively, was 37.4 and 27.6 months (0.72 [0.57-0.91]; P = 0.0044). Overall survival was similar in both arms; median was not reached (0.99 [0.72-1.37]). Grade ≥ 3 adverse events occurred in 62% and 51% of patients in ofatumumab and observation arms, respectively, the most common being neutropenia (23% and 10%), pneumonia (13% and 12%) and febrile neutropenia (6% and 4%). Up to 60 days after the last treatment, four deaths were reported in the ofatumumab arm versus six in the observation arm, none considered related to ofatumumab. Ofatumumab maintenance significantly prolonged progression-free survival in patients with relapsed CLL and was well tolerated.

• MeSH
• Leukemia, Lymphocytic, Chronic, B-Cell diagnosis   drug therapy   mortality   MeSH
• Adult MeSH
• Antibodies, Monoclonal, Humanized administration & dosage   adverse effects   therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Retreatment MeSH
• Antineoplastic Agents, Immunological administration & dosage   adverse effects   therapeutic use   MeSH
• Recurrence MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Maintenance Chemotherapy MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Names of Substances
• Antibodies, Monoclonal, Humanized MeSH
• ofatumumab MeSH Browser
• Antineoplastic Agents, Immunological MeSH