Magnetic resonance imaging (MRI) of the brain and spinal cord plays a crucial role in the diagnosis and monitoring of multiple sclerosis (MS). There is conclusive evidence that brain and spinal cord MRI findings in early disease stages also provide relevant insight into individual prognosis. This includes prediction of disease activity and disease progression, the accumulation of long-term disability and the conversion to secondary progressive MS. The extent to which these MRI findings should influence treatment decisions remains a subject of ongoing discussion. The aim of this review is to present and discuss the current knowledge and scientific evidence regarding the utility of MRI at early MS disease stages for prognostic classification of individual patients. In addition, we discuss the current evidence regarding the use of MRI in order to predict treatment response. Finally, we propose a potential approach as to how MRI data may be categorized and integrated into early clinical decision making.

Background:To reduce the risk of long-term disability in people with Multiple Sclerosis (pwMS), an increasing number of disease-modifying immune therapies (DMT) are available, involving diverse mechanisms of action, levels of efficacy, treatment risks, and tolerability aspects. Including patient preferences and expectations in shared decision-making may improve treatment satisfaction, adherence, and persistence.Purpose:To investigate long-term alignment of individual preferences and expectations of pwMS with their actual DMT and its effect on treatment satisfaction, health-related quality of life (HRQoL), adherence, and treatment discontinuation.Methods:A total of 401 pwMS beginning a new DMT were enrolled from 2015 to 2018 in a non-interventional study at three German MS centres. Patient preferences regarding DMT, TSQM-9, SF36, and self-reported adherence as well as relapses and EDSS were recorded at baseline and every 3 to 6 months for up to 3 years.Results:Efficacy and tolerability were the highest-ranking preferences at baseline. Actual selection of DMT corresponded more closely to safety than efficacy, tolerability, or convenience preferences. Participants reported excellent adherence throughout the study. DMT persistence was 69.0%, with earlier discontinuation for injectable vs oral or infusion therapies. Breakthrough disease, rather than patient-reported outcomes, was the main driver of DMT discontinuation. For all routes of administration, global treatment satisfaction increased over time despite lower satisfaction with convenience. Several patterns of changing preferences were observed.Conclusion:This study provides insight into the interaction of DMT preferences of pwMS with their actual treatment experience. Treatment decisions should be aligned with long-term expectations of pwMS to promote continuous adherence.

Purpose: The Harlequin syndrome may occur in patients treated with venoarterial extracorporal membrane oxygenation (VA-ECMO), in whom blood from the left ventricle and the ECMO system supply different parts of the body with different paCO2-levels. The purpose of this study was to compare two variants of paCO2-analysis to account for the Harlequin syndrome during apnea testing (AT) in brain death (BD) determination. Materials and methods: Twenty-seven patients (median age 48 years, 26-76 years; male n = 19) with VA-ECMO treatment were included who underwent BD determination. In variant 1, simultaneous arterial blood gas (ABG) samples were drawn from the right and the left radial artery. In variant 2, simultaneous ABG samples were drawn from the right radial artery and the postoxygenator ECMO circuit. Differences in paCO2-levels were analysed for both variants. Results: At the start of AT, median paCO2-difference between right and left radial artery (variant 1) was 0.90 mmHg (95%-confidence intervall [CI]: 0.7-1.3 mmHg). Median paCO2-difference between right radial artery and postoxygenator ECMO circuit (variant 2) was 3.3 mmHg (95%-CI: 1.5-6.0 mmHg) and thereby significantly higher compared to variant 1 (p = 0.001). At the end of AT, paCO2-difference according to variant 1 remained unchanged with 1.1 mmHg (95%-CI: 0.9-1.8 mmHg). In contrast, paCO2-difference according to variant 2 increased to 9.9 mmHg (95%-CI: 3.5-19.2 mmHg; p = 0.002). Conclusions: Simultaneous paCO2-analysis from right and left distal arterial lines is the method of choice to reduce the risk of adverse effects (e.g. severe respiratory acidosis) while performing AT in VA-ECMO patients during BD determination.

BACKGROUND:The revised Lublin classification offers a framework for categorizing multiple sclerosis (MS) according to the clinical course and imaging results. Diagnosis of secondary progressive MS (SPMS) is often delayed by a period of uncertainty. Several quantitative magnetic resonance imaging (qMRI) markers are associated with progressive disease states, but they are not usually available in clinical practice. METHODS:The MAGNON project enrolled 629 patients (early relapsing-remitting MS (RRMS), n = 51; RRMS with suspected SPMS, n = 386; SPMS, n = 192) at 55 centers in Germany. Routine magnetic resonance imaging (MRI) scans at baseline and after 12 months were analyzed using a centralized automatic processing pipeline to quantify lesions and normalized brain and thalamic volume. Clinical measures included relapse activity, disability, and MS phenotyping. Neurologists completed questionnaires before and after receiving the qMRI reports. RESULTS:According to the physicians' reports, qMRI results changed their assessment of the patient in 31.8% (baseline scan) and 27.6% (follow-up scan). For ∼50% of patients with RRMS with suspected SPMS, reports provided additional information that the patient was transitioning to SPMS. In >25% of all patients, this information influenced the physicians' assessment of the patient's current phenotype. However, actual changes of treatment were reported only in a minority of these patients. CONCLUSIONS:The MAGNON results suggest that standardized qMRI reports may be integrated into the routine clinical care of MS patients and support the application of the Lublin classification as well as treatment decisions. The highest impact was reported in patients with suspected SPMS, indicating a potential to reduce diagnostic uncertainty.

BACKGROUND:Computed tomography angiography (CTA) has been investigated as a confirmatory study (CS) for the diagnosis of brain death (BD). International consensus regarding its use, study parameters, and evaluation criteria is lacking. In the German BD guideline, a CTA protocol was first introduced in 2015. METHODS:The authors obtained a comprehensive dataset of all BD examinations in adults from the German organ procurement organization to investigate implementation, results, and impact of CTA on BD determination during the first 4 years. RESULTS:In 5152 patients with clinically absent brain function, 1272 CTA were reported by 676 hospitals. Use of CTA increased from 17.2% of patients in the first year to 29.7% in the final year. CTA replaced other CS such as electroencephalography without increasing overall CS frequency. Technical failure was rare (0.9%); 89.3% of studies were positive. Negative results (9.8%) were more frequent with secondary brain injury, longer duration of the clinical BD syndrome, or unreliable clinical assessment. Median time to diagnosis was longer with CTA (2.6 h) versus other CS (1.6 h). CTA had no differential impact on the rate of confirmed BD and did not improve access of small hospitals to CS for BD determination. CONCLUSIONS:CTA expands the range of available CS for the diagnosis of BD in adults. Real-world evidence from a large cohort confirms usability of the German CTA protocol within the guideline-specified context.

Objectives:We describe the development of Your Multiple Sclerosis Questionnaire and present the real-world usability testing results of Your Multiple Sclerosis Questionnaire. Methods:The Your Multiple Sclerosis Questionnaire tool was developed in four stages to collect feedback from people living with MS (plwMS), patient organizations, and clinicians on content, format, and applicability. To assess its usability, 13 clinicians across 7 countries completed an online survey after using the tool with plwMS in a total of 261 consultations from September, 2020 to July, 2021. Results:The initial Your Multiple Sclerosis Questionnaire version was based on findings from previous research developing MSProDiscuss™, a clinician-completed tool. Subsequently, insights from plwMS obtained during cognitive debriefing, patient councils and advisory boards led to changes including the addition of mood and sexual problems and the definition of relapse. All 13 clinicians completed the individual survey, whereas 10 clinicians completed the final survey. Clinicians "strongly agreed" or "agreed" that Your Multiple Sclerosis Questionnaire was easy to use and understand (98.5%; 257/261 patient consultations). The clinicians were willing to use the tool again with the same patient (98.1%; 256/261 patient consultations). All clinicians who completed the final survey (100%; 10/10) reported the tool to have a positive influence on their clinical practice, helped patients engage with their MS, facilitated discussion with patients, and complemented neurological assessment. Conclusion:Your Multiple Sclerosis Questionnaire benefits both plwMS and clinicians by facilitating a structured discussion and engaging the plwMS to self-monitor and self-manage. Your Multiple Sclerosis Questionnaire is compatible with telemedicine practice and integration of the tool into electronic health records would enable tracking of the disease evolution and individual monitoring of MS symptoms over time.

Objective: The non-interventional AMASIA study aims to provide real-world evidence on the long-term effectiveness and safety of siponimod on patients suffering from active secondary progressive multiple sclerosis (SPMS). Furthermore, the impact of siponimod-treatment on quality of life is also investigated. Background: The selective sphingosine-1-phosphate receptor modulator siponimod is approved for the treatment of relapsing forms of MS in the US and for the treatment of active SPMS in the EU. Real-word insights on the long-term effectiveness and safety of siponimod will support treatment decisions. Design/Methods: In this ongoing non-interventional study in Germany, siponimod treated active SPMS patients are followed over 3 years. Every 6 months, disability progression and cognitive changes are evaluated by EDSS, FSMC and SDMT. Questionnaires from the perspective of patients, physicians, and relatives on disability progression, cognitive worsening and quality of life are documented. The results correspond to the interim analyses as of June 2022 and February 2023. Results: Data collected from more than 600 active SPMS-patients receiving siponimod for the first time give an insight into the real-world clinical practice in Germany. Subgroup analyses by patient age, EDSS and time between diagnosis of MS and inclusion into this study indicate that siponimod exhibits a sustained effectiveness over the time studied (i.e. 18 months) in regard to preventing further progression of the disease as measured by EDSS, FSMC and SDMT. Younger patients and patients who start siponimod treatment earlier after the onset of their disease benefit slightly more. Regardless of age, TSQM scores "Effectiveness", "Convenience", and "Global Satisfaction" are at a high level throughout the observational period to date. Conclusions: AMASIA provides real-world evidence on the use of siponimod in the treatment of active SPMS patients in Germany, indicating a particular benefit for younger patients and patients who are treated early after the onset of the disease. Disclosure: Dr. Hoffmann has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Hoffmann has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Hoffmann has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hoffmann has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Hoffmann has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Hoffmann has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene. Dr. Hoffmann has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Hoffmann has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Hoffmann has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sandoz. Dr. Hoffmann has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Novartis. Dr. Hoffmann has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Hoffmann has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Merck. Dr. Hoffmann has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Roche. Dr. Hoffmann has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. The institution of Dr. Hoffmann has received research support from Biogen. The institution of Dr. Hoffmann has received research support from Novartis. The institution of Dr. Hoffmann has received research support from Sanofi. Herbert Schreiber has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Herbert Schreiber has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis . Herbert Schreiber has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Herbert Schreiber has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Herbert Schreiber has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche . Herbert Schreiber has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Almirall. Herbert Schreiber has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis . Herbert Schreiber has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Herbert Schreiber has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Teva. Herbert Schreiber has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Klotz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer. Dr. Klotz has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Klotz has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genzyme. Dr. Klotz has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Klotz has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck Serono. Dr. Klotz has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Klotz has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva. Dr. Klotz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Klotz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Klotz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Klotz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Klotz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Klotz has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Klotz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Klotz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Viatris. Dr. Klotz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BMS. The institution of Dr. Klotz has received research support from Immunic AG. The institution of Dr. Klotz has received research support from Merck. Martin Weber, MD has nothing to disclose. Dr. Weiss has received personal compensation for serving as an employee of Novartis Pharma GmbH. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BMS Celgene. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Roche. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Novartis. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Dr. Ziemssen has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sanofi. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for BMS Celgene. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for TEVA. The institution of Dr. Ziemssen has received research support from Biogen. The institution of Dr. Ziemssen has received research support from Novartis. The institution of Dr. Ziemssen has received research support from Merck. The institution of Dr. Ziemssen has received research support from Sanofi. The institution of Dr. Ziemssen has received research support from Celgene.

Zusammenfassung Hintergrund Seit Inkrafttreten der 4. Fortschreibung der Richtlinie der Bundesärztekammer gelten in Deutschland wesentliche neue Normierungen in der Diagnostik des irreversiblen Hirnfunktionsausfalls (IHA). Hierzu zählen die Qualifikationsanforderungen an die Untersucher, zugelassene Verfahren zur apparativen Zusatzdiagnostik und eine Präzisierung zur Abfolge der Prozessschritte. Fragestellung Untersuchung der Auswirkungen auf die Praxis der IHA-Feststellung. Methodik Deskriptive Auswertung der Dokumentation der Deutschen Stiftung Organtransplantation über IHA-Diagnostik im Vergleich der Zeiträume Juli 2011 bis Juni 2015 (3. Fortschreibung) und Juli 2015 bis Juni 2019 (4. Fortschreibung). Ergebnisse Die Zahl der erfassten Patienten sank von 6100 auf 5403. Die stärkste Abnahme betraf Krankenhäuser ohne Neurochirurgie. Kinder unter 14 Jahren waren nicht betroffen. Die klinische Diagnostik erfolgte ab Juli 2015 vermehrt im Bereitschaftsdienst durch externe neurologische Konsiliare. Zusatzdiagnostik erhielten nun 83,8 % der Patienten, zuvor 80,1 %. Die neu etablierte CTA wurde bei 23,2 % eingesetzt. Sie wies in 89,4 % den zerebralen Zirkulationsstillstand nach. Die Zeitdauer zwischen erstmaliger Feststellung der klinischen Ausfallzeichen und Feststellung des IHA stieg von 7,0 ± 12,7 h auf 8,2 ± 14,2 h. Der IHA wurde mit 95,3 % gegenüber 96,6 % geringfügig seltener festgestellt. Diskussion Die neuen Normierungen wurden richtlinienkonform umgesetzt. Der Bedarf an konsiliarischer Unterstützung durch Neurologen und Neurochirurgen sowie der Zeitbedarf für die IHA-Feststellung haben zugenommen. Negative Effekte auf die pädiatrische IHA-Diagnostik wurden nicht deutlich. Die CTA wird bei Erwachsenen als neues zusatzdiagnostisches Verfahren flächendeckend erfolgreich eingesetzt.

Background Ofatumumab is approved for treating relapsing multiple sclerosis (RMS). Examining tolerability will enable understanding of its risk–benefit profile. Objective Report the tolerability profile of ofatumumab in RMS during treatment of up to 4 years and the effect of pre-medication. Methods Cumulative data from the overall safety population included patients taking continuous ofatumumab or being newly switched from teriflunomide. Injection-related reactions (IRRs) by incidence and severity, and post-marketing surveillance data, with an exposure of 18,530 patient-years, were analyzed. Results Systemic IRRs affected 24.7% of patients (487/1969) in the overall safety population; most (99.2% [483/487]) were mild (333/487) to moderate (150/487) in Common Terminology Criteria for Adverse Events severity; most systemic IRRs occurred after first injection. Local-site IRRs affected 11.8% (233/1969) and most (99.6% [232/233]) were mild/moderate. Incidence and severity of systemic and localized IRRs were similar between continuous and newly switched patients across repeated injections. Systemic IRR incidence and severity were not substantially affected by steroidal or non-steroidal pre-medication. Post-marketing surveillance identified no new tolerability issues. Conclusion Ofatumumab is well tolerated, displays a consistent safety profile during continuous use or after switching from teriflunomide and does not require pre-medication. This enables home management of RMS with a high-efficacy treatment.

Purpose: We investigated cerebral perfusion pressure (CPP) at the time loss of cerebral blood flow (CBF) occurred during brain death (BD). We hypothesized that a critical closing pressure (CrCP) may be reached before CPP drops to 0 mmHg. Materials and methods: 14 patients with increasing intracranial pressure (ICP) leading to BD were included. Transcranial Duplex (TCD) ultrasonography was used to investigate CBF. Starting at a CPP of 30 mmHg, TCD was repeated until waveforms indicated loss of CBF. We then analyzed CPP by the time TCD indicated absent CBF and clinical BD was established. Results: In 12 patients, CPP was positive when clinical BD was manifest and TCD illustrated absent CBF. Across all patients, mean CPP at clinical BD manifestation was 10.0 mmHg (range 0-20 mmHg); mean CPP by the time CBF stopped was 7.5 mmHg (0-20 mmHg). In four patients, clinical BD preceded loss of CBF. Here, the mean CPP dif-ference from clinical BD to loss of CBF was 8.8 mmHg (5-15 mmHg). Conclusions: CrCP may be reached although CPP is still positive, resulting in complete loss of CBF and BD. By in-cluding bedside TCD, neuromonitoring may contribute to early identification of patients at risk to experience loss of CBF and subsequent BD. (c) 2022 Elsevier Inc. All rights reserved.

The Your Multiple Sclerosis Questionnaire (YMSQ; www.yourms.com), a patient-completed tool, was co-developed with people living with MS (plwMS), patient advocacy groups, and clinicians to capture MS symptom changes and facilitate discussion between plwMS and clinicians. We describe the development of YMSQ and present the real-world usability testing results of YMSQ conducted across 7 countries. The YMSQ tool was developed in 4 stages to collect feedback from plwMS, patient organizations, and clinicians on content, format, and applicability. To assess its usability, 13 clinicians across 7 countries completed an online survey after using the tool with plwMS in a total of 261 consultations from September, 2020 to July, 2021. The initial YMSQ version was based on findings from previous research developing MSProDiscuss™, a clinician-completed tool. Subsequently, insights from plwMS obtained during cognitive debriefing, patient councils and advisory boards led to changes including the addition of mood and sexual problems and the definition of relapse. All 13 clinicians completed the individual survey, whereas 10 clinicians completed the final survey. Clinicians “strongly agreed” or “agreed” that YMSQ was easy to use and understand (98.5%; 257/261 patient consultations). The clinicians were willing to use the tool again with the same patient (98.1%; 256/261 patient consultations). All clinicians who completed the final survey (100%; 10/10) reported that the use of the tool had a positive influence on their clinical practice, helped patients engage with their MS, facilitated discussion with patients, and complemented neurological assessment. YMSQ benefits both plwMS and clinicians by facilitating a structured discussion and engaging the plwMS to self-monitor and self-manage. YMSQ is compatible with telemedicine practice and integration of the tool into electronic health records would enable tracking of the disease evolution and individual monitoring of MS symptoms over time.

Objective To characterize the risk of injection-related reactions (IRRs: systemic and local-site) observed in relapsing multiple sclerosis (RMS) patients treated with ofatumumab in clinical trials and post-marketing surveillance. Methods Data from patients treated with ofatumumab in the core ASCLEPIOS I/II trials and ALITHIOS study (overall, N=1969; patients who received continuous ofatumumab, N=1292; patients newly switched from teriflunomide to ofatumumab, N=677) and post-marketing surveillance (cut-off: 29-Jan-2021) were included in the analysis. Incidence of both systemic and local-site IRRs, their severity and seriousness were reported. Results Systemic/local-site IRRs were observed in 24.6%/11.5% in overall; 25.6%/13.2% in continuous and 22.6%/8.3% in newly-switched groups. Upon first injection, incidence of systemic/local-site IRRs in overall, continuous, and newly-switched groups were 17.4%/2.9%, 17%/3.4%, and 18.2%/2.1%, respectively. Majority (99.5%) were mild-to-moderate (Grade 1/2) in severity. No life-threatening IRRs were observed during the study. In the overall population, systemic and local-site IRRs led to treatment discontinuation in 5 and 1 patient, respectively. The most common systemic IRR symptoms (≥5%) with all injections were fever, headache, chills, fatigue, and local site IRR symptoms (≥3%) were erythema/redness and pain. From the post-marketing, 6 serious cases were assessed as potential systemic IRRs (HCP/non-HCP: 2/4): 1 patient was hospitalized with weakness. In addition, 5 patients reported serious hypersensitivity reactions (HCP/non-HCP: 1/4) including 1 anaphylaxis. Conclusions Systemic and local-site IRRs reported upon first injection with ofatumumab in the ALITHIOS trial and post-marketing surveillance were mostly mild-to-moderate in severity. These results are consistent with the Phase 3 ASCLEPIOS I/II trials.

To characterize the risk of injection-related reactions (IRRs: systemic and local-site) observed in relapsing multiple sclerosis (RMS) patients treated with ofatumumab in clinical trials and post-marketing surveillance.

Zusammenfassung Die Multiple Sklerose ist eine komplexe, autoimmun vermittelte Erkrankung des zentralen Nervensystems, charakterisiert durch inflammatorische Demyelinisierung sowie axonalen/neuronalen Schaden. Die Zulassung verschiedener verlaufsmodifizierender Therapien und unser verbessertes Verständnis der Krankheitsmechanismen und -entwicklung in den letzten Jahren haben die Prognose und den Verlauf der Erkrankung deutlich verändert. Diese Aktualisierung der Behandlungsempfehlung der Multiple Sklerose Therapie Konsensus Gruppe konzentriert sich auf die wichtigsten Empfehlungen für verlaufsmodifizierende Therapien der Multiplen Sklerose im Jahr 2021. Unsere Empfehlungen basieren auf aktuellen wissenschaftlichen Erkenntnissen und gelten für diejenigen Medikamente, die in weiten Teilen Europas, insbesondere in den deutschsprachigen Ländern (Deutschland, Österreich, Schweiz), zugelassen sind.

Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particularly German-speaking countries (Germany, Austria, and Switzerland).

Background Multiple sclerosis (MS) is a disease continuum from a clinically isolated syndrome through relapsing remitting MS to secondary progressive MS (SPMS). There are numerous therapeutic approaches with proven efficacy on relapse and focal inflammatory disease aspects, whereas treatment of secondary progression and associated neuropathological aspects continues to be a challenge. Objective Overview of the current options for disease-modifying treatment of SPMS. Material and methods Results of randomized clinical trials are presented and evaluated on a substance-specific basis. Results Randomized SPMS trials showed inconsistent results regarding disability progression for beta interferons and negative results for natalizumab. Oral cladribine and ocrelizumab reduced disability progression in relapsing MS but have not been specifically studied in an SPMS population. Positive results for mitoxantrone are only partially applicable to current SPMS patients. For siponimod, a substance that crosses the blood-brain barrier, the EXPAND trial demonstrated a significant reduction in the risk of disability progression in typical SPMS. Subgroup analyses suggest a higher efficacy of siponimod in younger patients with active SPMS. Conclusion There is limited evidence for the use of previously available disease-modifying treatment in SPMS. Siponimod represents a new therapeutic option for active SPMS, defined by relapses or focal inflammatory MRI activity. To establish the therapeutic indications for siponimod, early detection of relapse-independent progression as well as differentiation of active SPMS from inactive disease are of critical importance.