The current standing of autologous haematopoietic stem cell transplantation for the treatment of multiple sclerosis.

Autologous haematopoietic stem cell transplantation (aHSCT) is gaining traction as a valuable treatment option for patients affected by severe multiple sclerosis (MS), particularly the relapsing-remitting form. We describe the current literature in terms of clinical trials, observational and retrospective studies, as well as immune reconstitution following transplantation, with a focus on the conditioning regimens used for transplantation. The evidence base predominantly consists of non-randomised, uncontrolled clinical trials or data from retrospective or observational cohorts, i.e. very few randomised or controlled trials. Most often, intermediate-intensity conditioning regimens are used, with promising results from both myeloablative and lymphoablative strategies, as well as from regimens that are low and high intensity. Efficacy of transplantation, which is likely secondary to immune reconstitution and restored immune tolerance, is, therefore, not clearly dependent on the intensity of the conditioning regimen. However, the conditioning regimen may well influence the immune response to transplantation. Heterogeneity of conditioning regimens among studies hinders synthesis of the articles assessing post-aHSCT immune system changes. Factors associated with better outcomes were lower Kurtzke Expanded Disability Status Scale, relapsing-remitting MS, younger age, and shorter disease duration at baseline, which supports the guidance for patient selection proposed by the European Society for Blood and Marrow Transplantation. Interestingly, promising outcomes were described for patients with secondary progressive MS by some studies, which may be worth taking into account when considering treatment options for patients with active, progressive disease. Of note, a significant proportion of patients develop autoimmune disease following transplantation, with alemtuzumab-containing regimens associated with the highest incidence.

Effects of disease-modifying therapy on peripheral leukocytes in patients with multiple sclerosis.

Modern disease-modifying therapies (DMTs) in multiple sclerosis (MS) have variable modes of action and selectively suppress or modulate the immune system. In this review, we summarize the predicted and intended as well as unwanted adverse effects on leukocytes in peripheral blood as a result of treatment with DMTs for MS. We link changes in laboratory tests to the possible therapeutic risks that include secondary autoimmunity, infections, and impaired response to vaccinations. Profound knowledge of the intended effects on leukocyte counts, in particular lymphocytes, explained by the mode of action, and adverse effects which may require additional laboratory and clinical vigilance or even drug discontinuation, is needed when prescribing DMTs to treat patients with MS.

Shorter infusion time of ocrelizumab: Results from the randomized, double-blind ENSEMBLE PLUS substudy in patients with relapsing-remitting multiple sclerosis.

BACKGROUND: Ocrelizumab is an approved intravenously administered anti-CD20 antibody for multiple sclerosis (MS). Shortening the 600 mg infusion to 2 hours reduces the total site stay from 5.5-6 hours (approved infusion duration including mandatory pre-medication and post-infusion observation) to 4 hours. The safety profile of shorter-duration ocrelizumab infusions was investigated using results from ENSEMBLE PLUS. METHODS: ENSEMBLE PLUS is a randomized, double-blind substudy to the single-arm ENSEMBLE study (NCT03085810). In ENSEMBLE, patients with early-stage relapsing-remitting MS received ocrelizumab 600 mg infusions every 24 weeks for 192 weeks. In ENSEMBLE PLUS, ocrelizumab 600 mg administered over the approved 3.5-hour infusion time (conventional duration) is compared with a 2-hour infusion (shorter duration); the durations of the initial infusions (2×300 mg, 14 days apart) were unaffected. The primary endpoint was the proportion of patients with infusion-related reactions (IRRs) following the first Randomized Dose. RESULTS: From November 1, 2018, to December 13, 2019, 745 patients were randomized 1:1 to the conventional or shorter infusion group. At the first Randomized Dose, 99/373 patients (26.5%) in the conventional and 107/372 patients (28.8%) in the shorter infusion group experienced IRRs. The majority of IRRs were mild or moderate; >99% of all IRRs resolved without sequelae in both groups (conventional infusion group, 99/99; shorter infusion group, 106/107). No IRRs were serious, life-threatening, or fatal. No IRR-related discontinuations occurred. During the first Randomized Dose, 22/373 (5.9%) and 39/372 (10.5%) patients in the conventional and shorter infusion groups, respectively, had IRRs leading to infusion slowing/interruption. Adverse events were consistent with the known safety profile of ocrelizumab. CONCLUSION: The rates and severity of IRRs were similar between conventional and shorter infusions. No new safety signals were detected. Shortening the infusion time to 2 hours reduces the total site stay time (including mandatory pre-medication/infusion/observation) from 5.5-6 hours to 4 hours, and may reduce patient and site staff burden. A short video summarizing the key results is provided in supplemental material.

Patient-reported outcomes with subcutaneous immunoglobulin in chronic inflammatory demyelinating polyneuropathy: the PATH study.

BACKGROUND AND PURPOSE: Chronic inflammatory demyelinating polyneuropathy (CIDP) causes weakness which adversely impacts function and quality of life (QOL). CIDP often requires long-term management with intravenous or subcutaneous immunoglobulin. The Polyneuropathy and Treatment with Hizentra® (PATH) study showed that subcutaneous immunoglobulin (SCIG) was efficacious in CIDP maintenance. Here, patient-reported outcomes in patients on SCIG are assessed. METHODS: Subjects stabilized on intravenous immunoglobulin were randomly allocated to receive weekly 0.2 or 0.4 g/kg bodyweight of 20% SCIG (IgPro20) or placebo. Overall QOL/health status was assessed using the EuroQoL 5-Dimension (EQ-5D) health profile and visual analog scale, treatment satisfaction was assessed with the Treatment Satisfaction Questionnaire for Medicine (TSQM) and work-related impact was assessed with the Work Productivity and Activity Impairment Questionnaire for General Health (WPAI-GH). The EQ-5D health profile was assessed in terms of the percentage of subjects maintained or improved at week 25 of SCIG therapy on each of the EQ-5D domains versus baseline after intravenous immunoglobulin stabilization. TSQM and WPAI-GH were assessed by median score changes from baseline to week 25. RESULTS: In total, 172 subjects were randomized to placebo (n = 57), 0.2 g/kg IgPro20 (n = 57) and 0.4 g/kg IgPro20 (n = 58). Significantly higher proportions of IgPro20-treated subjects improved/maintained their health status on the EQ-5D usual activities dimension, and in additional dimensions (mobility and pain/discomfort) in sensitivity analyses. TSQM and WPAI-GH scores were more stable with IgPro20 treatment compared with placebo. CONCLUSIONS: IgPro20 maintained or improved QOL in most subjects with CIDP, consistent with the PATH study findings that both IgPro20 doses were efficacious in maintaining CIDP.

[Diagnosis of multiple sclerosis: revision of the McDonald criteria 2017]. / Diagnose der Multiplen Sklerose: Revision der McDonald-Kriterien 2017.

Multiple sclerosis (MS) is the most common chronic autoimmune disorder of the central nervous system (CNS) largely affecting young adults. The diagnosis of MS is based on two pillars: 1) detection of the spatial and temporal dissemination of focal neurological deficits and 2) exclusion of important differential diagnoses. The current revision of the diagnostic criteria (McDonald 2017) also follows these principles, takes new data on magnetic resonance imaging (MRI) into account and reintroduces the role of cerebrospinal fluid (CSF) diagnostics for relapsing-remitting forms. The main priority is a reliable diagnosis as early as possible with the aim of a timely initiation of course-adapted treatment. Some of the concrete innovations are the consideration of cortical MRI lesions (equivalent to juxtacortical foci), the elimination of a distinction between asymptomatic and symptomatic MRI lesions and consideration of characteristic CSF findings for the criterion of temporal dissemination. Relapsing MS can be diagnosed at the time of the first attack by the detection of CSF-specific oligoclonal bands and the MRI detection of a typical local lesion distribution (even without simultaneous detection of a contrast-enhancing lesion). For the primary progressive course, for which a first treatment option has recently been approved, the known definition remains unaltered. With respect to the differential diagnosis there is a clear demarcation from Devic's syndrome, now known as neuromyelitis optica spectrum disorders (NMOSD), as recent insights indicate a separate disease entity caused by an autoimmune response against the astrocytic aquaporin 4 (AQP4) water channel. Finally, future studies will have to provide a definition for secondary progressive MS courses and clarify how to handle diseases characterized by antibodies against myelin oligodendrocyte glycoprotein (MOG) or patients with radiologically isolated syndrome (RIS), i. e. incidental MRI-based detection of CNS lesions in the absence of any clinical event. In summary, McDonald 2017 is within the conceptual structure of its predecessor and simplifies an early diagnosis, thus paving the way to early treatment of MS.

Cerebrospinal fluid findings in reversible cerebral vasoconstriction syndrome: a way to differentiate from cerebral vasculitis?

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by an acute onset of severe headache and multi-focal segmental vasoconstriction of cerebral arteries resolving within 12 weeks. Diagnostic criteria include normal or near-normal findings in cerebrospinal fluid (CSF) analysis, especially leucocyte levels < 10/mm³. Distinguishing RCVS from primary angiitis of the central nervous system (PACNS) is essential to avoid unnecessary and sometimes unfavourable immunosuppressive treatment. We reviewed retrospectively the clinical and diagnostic data of 10 RCVS patients who presented in our neurological department from 1 January 2013 to February 2017. The main purpose was to verify whether CSF leucocyte counts < 10/mm³ serve to discriminate RCVS from PACNS. Five of six patients who underwent lumbar puncture presented with CSF leucocyte levels ≥ 10/mm³. Two patients had a history of misinterpretation of CSF pleocytosis as cerebral vasculitis and of immunosuppressive treatment. A complete restitution of cerebral vasoconstriction was evident in all. No patient had further cerebral strokes or bleedings without immunosuppressive treatment over more than 12 weeks. Despite the established diagnostic criteria, RCVS can manifest with CSF leucocyte levels > 10/mm³. Careful anamnesis and the response of 'vasculitis-like angiography' to nimodipine given as a test during angiography and as oral medication are key to differentiate RCVS from cerebral vasculitis.

[Cladribine tablets : Oral immunotherapy of relapsing-remitting multiple sclerosis with short yearly treatment periods]. / Cladribin-Tabletten : Orale Immuntherapie der schubförmigen Multiplen Sklerose mit kurzen, jährlichen Behandlungsphasen.

BACKGROUND: The selective modulation of lymphocyte numbers and function is an attractive concept in the treatment of relapsing-remitting multiple sclerosis (RMS). OBJECTIVE: Cladribine tablets (Mavenclad®), an oral RMS medication with an innovative treatment concept, have been available since August 2017. This review article summarizes the currently available clinical study data on cladribine tablets and aspects of their use in clinical practice. RESULTS: Cladribine tablets are administered during two treatment phases of 8-10 (two times 4-5) days with a 1-year interval. The drug selectively reduces the number of T and B lymphocytes, which are subsequently gradually reconstituted with divergent kinetics. A pronounced and sustained effect on the clinical and paraclinical MS disease activity is achieved with good tolerability and a favorable overall safety profile. After completing the two short treatment phases, a relevant proportion of the treated patients experience a prolonged treatment-free period with absence of relevant disease activity. Regular monitoring of lymphocyte counts and reliable contraception during the required time frames are the most important safety measures. There is no evidence of an increased risk of malignancies. CONCLUSION: Cladribine tablets are an important addition to the therapeutic landscape in RMS. With patient-friendly short dosing periods and a favorable adverse event profile, cladribine tablets provide a sustained and strong reduction of MS disease activity. The primary target population for cladribine tablets is patients with relevant MS disease activity (highly active RMS) while on first-line treatment, e. g. with injectable disease-modifying drugs.

[Multiple sclerosis and hepatitis B vaccination : What does the verdict of the European Court of Justice on liability after vaccination mean?] / Multiple Sklerose und Hepatitis-B-Impfung : Was bedeutet das Urteil des EuGH zur Haftung nach Impfung?

In June 2017 the European Court of Justice (ECJ) issued a verdict on the legal assessment of the association between hepatitis B immunization and the subsequent manifestation of multiple sclerosis (MS). This led to a high level of insecurity in the medical field as well as the normal population, especially in MS patients. The aim of this article is to briefly present the evidence-based medical facts and in particular to clearly highlight the legal aspects of the abovenamed ECJ verdict.

ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is a complex disease of the central nervous system. As new drugs are becoming available, knowledge on diagnosis and treatment must continuously evolve. There is therefore a need for a reference tool compiling current data on benefit and safety, to aid professionals in treatment decisions and use of resources across Europe. The European Committee of Treatment and Research in Multiple Sclerosis (ECTRIMS) and the European Academy of Neurology (EAN) have joined forces to meet this need. The objective was to develop an evidence-based clinical practice guideline for the pharmacological treatment of people with MS to guide healthcare professionals in the decision-making process. METHODS: This guideline has been developed using the GRADE methodology and following the recently updated EAN recommendations for guideline development. Clinical questions were formulated in PICO format (patient, intervention, comparator, outcome) and outcomes were prioritized according to their relevance to clinical practice. An exhaustive literature search up to December 2016 was performed for each question and the evidence is presented narratively and, when possible, combined in a meta-analysis using a random-effects model. The quality of evidence for each outcome was rated into four categories - very high, high, low and very low - according to the risk of bias. GRADE evidence profiles were created using GRADEprofiler (GRADEpro) software (Version 3.6). The recommendations with assigned strength (strong, weak) were formulated based on the quality of evidence and the risk-benefit balance. Consensus between the panellists was reached by use of the modified nominal group technique. RESULTS: A total of 10 questions have been agreed, encompassing treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns and treatment strategies in MS and pregnancy. The guideline takes into account all disease-modifying drugs approved by the European Medicine Agency at the time of publication. A total of 20 recommendations were agreed by the guideline working group members after three rounds of consensus.

Survey of diagnostic and treatment practices for multiple sclerosis (MS) in Europe. Part 2: Progressive MS, paediatric MS, pregnancy and general management.

BACKGROUND AND PURPOSE: The European Charcot Foundation supported the development of a set of surveys to understand current practice patterns for the diagnosis and management of multiple sclerosis (MS) in Europe. Part 2 of the report summarizes survey results related to secondary progressive MS (SPMS), primary progressive MS (PPMS), pregnancy, paediatric MS and overall patient management. METHODS: A steering committee of MS neurologists developed case- and practice-based questions for two sequential surveys distributed to MS neurologists throughout Europe. RESULTS: Respondents generally favoured changing rather than stopping disease-modifying treatment (DMT) in patients transitioning from relapsing-remitting MS to SPMS, particularly with active disease. Respondents would not initiate DMT in patients with typical PPMS symptoms, although the presence of ≥1 spinal cord or brain gadolinium-enhancing lesion might affect that decision. For patients considering pregnancy, respondents were equally divided on whether to stop treatment before or after conception. Respondents strongly favoured starting DMT in paediatric MS with active disease; recommended treatments included interferon, glatiramer acetate and, in John Cunningham virus negative patients, natalizumab. Additional results regarding practice-based questions and management are summarized. CONCLUSIONS: Results of part 2 of the survey of diagnostic and treatment practices for MS in Europe largely mirror results for part 1, with neurologists in general agreement about the treatment and management of SPMS, PPMS, pregnancy and paediatric MS as well as the general management of MS. However, there are also many areas of disagreement, indicating the need for evidence-based recommendations and/or guidelines.

Late age onset of amyotrophic lateral sclerosis is often not considered in elderly people.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease causing an upper and lower motor neuron loss. It is neurology textbook knowledge that the mean age of onset is about 60 years. However, recent investigations show an increasing incidence in older persons. We therefore evaluated whether ALS is potentially not considered in elderly people with ALS symptoms, respectively, not recognized. MATERIALS AND METHODS: We included retrospectively all patients with ALS diagnoses after work-up that were admitted to our neurological and geriatric departments from 2007 to 2010 and collected their clinical data. The diagnosis of ALS was based on the El Escorial criteria. Patients were grouped into three categories according to age (<50, between 50 and 70, >70), and differences in clinical and/ or biographical factors were investigated. RESULTS: We identified 35 patients (18 men and 17 women) with a median age at onset of 71.5 years (range: 36-87 years). When establishing the diagnosis, 51% were older than 70 years, 40% (14/35) between 50 and 70, and only 9% younger than 50. Only in 46 per cent of patients who were sent to our departments with ALS symptoms ALS was considered by the referring physician. CONCLUSION: Late age onset of ALS seems to be more common than formerly assumed and is presumably under-recognized in elderly patients. ALS needs to be considered as a differential diagnosis in older patients. Potential factors accounting for older people being underdiagnosed with ALS relate to frequent presentation with symptoms like dysphagia, frailty or general weakness for other reasons.

Survey of diagnostic and treatment practices for multiple sclerosis in Europe.

BACKGROUND AND PURPOSE: Up-to-date information is needed on the extent to which neurologists treating multiple sclerosis (MS) in Europe are integrating rapidly evolving diagnostic criteria, disease-modifying therapies and recommendations for monitoring disease activity into their clinical practice. METHODS: A steering committee of MS neurologists used a modified Delphi process to develop case- and practice-based questions for two sequential surveys distributed to MS neurologists throughout Europe. Case-based questions were developed for radiologically isolated syndrome (RIS), clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS) and RRMS with breakthrough disease. RESULTS: Multiple sclerosis neurologists from 11 European countries responded to survey 1 (n = 233) and survey 2 (n = 171). Respondents agreed that they would not treat the patients in the RIS or CIS cases but would treat a patient with a relatively mild form of RRMS. Choice of treatment was evenly distributed among first-line injectables and oral treatments for mild RRMS, and moved to second-line treatment as the RRMS case increased in severity. Additional results on RRMS with breakthrough disease are presented. CONCLUSIONS: Although there was general agreement on some aspects of treatment, responses to other management and clinical practice questions varied considerably. These results, which reflect current clinical practice patterns, highlight the need for additional MS treatment education and awareness and may help inform the development of MS practice guidelines in Europe.

[Progressive multifocal leukoencephalopathy]. / Progressive multifokale Leukenzephalopathie.

Progressive multifocal leukoencephalopathy (PML) is a disease of immunosuppressed patients caused by the JC polyomavirus (JCPyV). Due to the elevated risk in patients treated with natalizumab for multiple sclerosis (MS) and also treatment with other biologicals for different indications, the relevance of PML has increased in recent years. This article summarizes the published knowledge on the biology and pathogenesis of PML with a focus on the role of cerebrospinal fluid diagnostics in the work-up for PML and the current PML case definition. Current recommendations regarding risk management are discussed, as are possible therapies and prevention.

[Hermann Oppenheim. Comments on his life and works]. / Hermann Oppenheim. Anmerkungen zu seinem Leben und Wirken.

The outstanding neurologist Hermann Oppenheim was renowned worldwide during his lifetime and was highly esteemed; however, he was also a contradictory, complex personality and his life was marked by several tragic events. Even for his contemporaries, his life and work was the subject of lively discussions and debates and also some 100 years later, it is an interesting challenge to obtain an insight into the extensive work of this famous man and to understand the reasons for his great successes and failures.

Safety and efficacy of dimethyl fumarate in multiple sclerosis: a multi-center observational study.

Dimethyl fumarate (DMF) was recently approved for treating patients with relapsing-remitting multiple sclerosis (RRMS) based on two phase III clinical trials demonstrating its efficacy. This prompts the need for demonstrating the clinical efficacy and safety of DMF in the real world. By retrospective analysis of medical records at two German MS centers, 644 MS patients treated with DMF were identified. All were included in a safety analysis, and a subgroup of patients with available efficacy data during previous MS therapies (n = 352) was further analyzed for annualized relapse rate and disability progression assessed by the EDSS. In the overall DMF population studied, the annualized relapse rate decreased from 0.52 at baseline to 0.35, and the annualized disability progression from 0.15 to 0.10. Patients who were switched from interferons or glatiramer acetate to DMF revealed a greater benefit, whereas patients pretreated with more potent immunotherapies did not respond that well. Interestingly, patients with a lymphocyte count ≥2000/µl after 0.52 years (mean, SD 0.2) of DMF treatment did not benefit compared to those with lower lymphocyte counts. In total, 22.2 % of the patients withdrew from DMF due to side effects, with gastrointestinal discomfort (12.7 %) and lymphopenia (5.3 %) as most frequently reported reasons. Our study corroborates that DMF is an overall safe and effective drug that reduces relapse rate as well as disability progression in MS patients. Further prospective studies are warranted to establish the additional parameters predicting DMF response, especially in patients switching from other first-line immunotherapies.

Dual roles of the adenosine A2a receptor in autoimmune neuroinflammation.

BACKGROUND: Conditions of inflammatory tissue distress are associated with high extracellular levels of adenosine, due to increased adenosine triphosphate (ATP) degradation upon cellular stress or the release of extracellular ATP upon cell death, which can be degraded to adenosine by membrane-bound ecto-enzymes like CD39 and CD73. Adenosine is recognised to mediate anti-inflammatory effects via the adenosine A2a receptor (A2aR), as shown in experimental models of arthritis. Here, using pharmacological interventions and genetic inactivation, we investigated the roles of A2aR in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). METHODS: We used two independent mouse EAE variants, i.e. active immunization in C57BL/6 with myelin oligodendrocyte glycoprotein (MOG)35-55 or transfer-EAE by proteolipid protein (PLP)139-155-stimulated T lymphocytes and EAE in mice treated with A2aR-agonist CGS21680 at different stages of disease course and in mice lacking A2aR (A2aR(-/-)) compared to direct wild-type littermates. In EAE, we analysed myelin-specific proliferation and cytokine synthesis ex vivo, as well as inflammation and demyelination by immunohistochemistry. In vitro, we investigated the effect of A2aR on migration of CD4(+) T cells, macrophages and microglia, as well as the impact of A2aR on phagocytosis of macrophages and microglia. Statistical tests were Mann-Whitney U and Student's t test. RESULTS: We found an upregulation of A2aR in the central nervous system (CNS) in EAE, predominantly detected on T cells and macrophages/microglia within the inflamed tissue. Preventive EAE treatment with A2aR-specific agonist inhibited myelin-specific T cell proliferation ex vivo and ameliorated disease, while application of the same agonist after disease onset exacerbated non-remitting EAE progression and resulted in more severe tissue destruction. Accordingly, A2aR-deficient mice showed accelerated and exacerbated disease manifestation with increased frequencies of IFN-γ-, IL-17- and GM-CSF-producing CD4(+) T helper cells and higher numbers of inflammatory lesions in the early stage. However, EAE quickly ameliorated and myelin debris accumulation was lower in A2aR(-/-) mice. In vitro, activation of A2aR inhibited phagocytosis of myelin by macrophages and primary microglia as well as migration of CD4(+) T cells, macrophages and primary microglia. CONCLUSIONS: A2aR activation exerts a complex pattern in chronic autoimmune neurodegeneration: while providing anti-inflammatory effects on T cells and thus protection at early stages, A2aR seems to play a detrimental role during later stages of disease and may thus contribute to sustained tissue damage within the inflamed CNS.

[Current aspects of therapy conversion for multiple sclerosis]. / Aktuelles zur Therapieumstellung bei Multipler Sklerose.

In recent years the approval of new substances has led to a substantial increase in the number of course-modifying immunotherapies available for multiple sclerosis. Therapy conversion therefore represents an increasing challenge. The treatment options sometimes show complex adverse effect profiles and necessitate a long-term and comprehensive monitoring. This article presents an overview of therapy conversion of immunotherapies for multiple sclerosis in accordance with the recommendations of the Disease-Related Competence Network for Multiple Sclerosis and the German Multiple Sclerosis Society as well as the guidelines on diagnostics and therapy for multiple sclerosis of the German Society of Neurology and the latest research results. At the present point in time it should be noted that no studies have been carried out for most of the approaches for therapy conversion given here; however, the recommendations are based on theoretical considerations and therefore correspond to recommendations at the level of expert consensus, which is currently essential for the clinical daily routine.

[Infection risks in multiple sclerosis therapy by infusion of disease modifying drugs]. / Infektiologische Risiken in der Multiple-Sklerose-Therapie durch infundierbare Immuntherapeutika.

The increased risk of developing infections when using disease-modifying drugs for treatment of multiple sclerosis (MS) is a major challenge in the daily clinical routine. In the growing field of treatment options specific knowledge of treatment-related risks of infections and appropriate preventive and countermeasures is mandatory. Current clinical experience shows that an individual risk stratification is necessary when choosing treatment options and while monitoring during and after treatment administration. The determination of the individual risk of infection in the context of serial use of disease-modifying drugs remains a challenging issue. In addition to the mechanisms of action, the warning notices and current recommendations on infection prophylaxis when using intravenous disease-modifying drugs, such as alemtuzumab, natalizumab and mitoxantron, are presented in detail.

[Immunotherapy and infectious issues in multiple sclerosis. Self-injectable and oral drugs for immunotherapy]. / Immuntherapien und infektiologische Probleme bei Multipler Sklerose. Selbst injizierbare und orale Immuntherapeutika.

Immunotherapy is generally associated with an increased risk for the development of infections. Due to the continuously expanding spectrum of new and potent immunotherapy treatment options for multiple sclerosis (MS), this article describes the currently known risks for treatment-related infections and the current recommendations for prevention of corresponding problems with drugs used in treatment strategies for MS and their mechanisms of action. The new treatment options in particular are linked to specific and severe infections; therefore, intensive and long-lasting monitoring is required before, during and after treatment and multidisciplinary surveillance of patients is needed. This article gives a detailed review of drug-specific red flags and current recommendations for the prophylaxis of infections associated with treatment of relapsing-remitting MS and when using self-injectable and oral disease-modifying immunotherapeutic drugs.