Interferon beta-1a sc at 25 years: a mainstay in the treatment of multiple sclerosis over the period of one generation.

INTRODUCTION Interferon beta (IFN beta) preparations are an established group of drugs used for immunomodulation in patients with multiple sclerosis (MS). Subcutaneously (sc) applied interferon beta-1a (IFN beta-1a sc) has been in continuous clinical use for 25 years as a disease-modifying treatment. AREAS COVERED Based on data published since 2018, we discuss recent insights from analyses of the pivotal trial PRISMS and its long-term extension as well as from newer randomized studies with IFN beta-1a sc as the reference treatment, the use of IFN beta-1a sc across the patient life span and as a bridging therapy, recent data regarding the mechanisms of action, and potential benefits of IFN beta-1a sc regarding vaccine responses. EXPERT OPINION IFN beta-1a sc paved the way to effective immunomodulatory treatment of MS, enabled meaningful insights into the disease process, and remains a valid therapeutic option in selected vulnerable MS patient groups

Incidence and mitigation of gastrointestinal events in patients with relapsing–remitting multiple sclerosis receiving delayed-release dimethyl fumarate: a German phase IV study (TOLERATE)

Background: Gastrointestinal (GI) events are common adverse events (AEs) associated with delayed-release dimethyl fumarate (DMF), an approved treatment for relapsing–remitting multiple sclerosis (RRMS). The objective of the TOLERATE study was to evaluate GI tolerability and GI mitigation via symptomatic therapies in patients initiating DMF in a real-world clinical setting in Germany. Methods: TOLERATE was a multicentre, open-label, single-arm study performed at 25 German sites. Endpoints were frequency, severity, duration (all primary) and mitigation of GI-related events (secondary). Patients were instructed to take DMF according to the prescribing information for up to 12 weeks and to document GI events and intake of GI-symptomatic therapy on numerical rating scales, using eDiaries. Results: A total of 211 patients were included in the safety population (71% female; mean age 40 ± 11 years). Of these, 185 patients (87.7%) reported GI-related events, out of which nearly half received GI-symptomatic therapy (84/185; 45.4%). The most frequently reported GI events were upper abdominal pain, flatulence and nausea. GI-related events peaked during the first 3 weeks of therapy and rapidly decreased thereafter. The severity of GI events over 12 weeks according to the Modified Overall Gastrointestinal Symptom Scale were mild to moderate in the majority of patients reporting GI-related events and taking symptomatic GI medication (53.6%). Only 10% of all patients discontinued study treatment due to AEs in general, while 6.6% discontinued due to GI-related events. The severity of GI-related events decreased over time in patients who received symptomatic treatment with one or more medications (e.g. acid secretion blockers, antidiarrhoeals or antiemetics). Conclusion: Gastrointestinal events associated with delayed-release DMF were mainly mild to moderate in severity. Prevalence of GI events peaked during the first 3 weeks of therapy and rapidly faded thereafter. Although 44.9% of patients experiencing GI events used common GI symptomatic therapies, only 6.6% of patients discontinued DMF because of GI events, suggesting that GI events could be managed well with common symptomatic therapy

Control of SARS-CoV-2 infection in rituximab-treated neuroimmunological patients

Background!#!Diagnostic classification of central vs. peripheral etiologies in acute vestibular disorders remains a challenge in the emergency setting. Novel machine-learning methods may help to support diagnostic decisions. In the current study, we tested the performance of standard and machine-learning approaches in the classification of consecutive patients with acute central or peripheral vestibular disorders.!##!Methods!#!40 Patients with vestibular stroke (19 with and 21 without acute vestibular syndrome (AVS), defined by the presence of spontaneous nystagmus) and 68 patients with peripheral AVS due to vestibular neuritis were recruited in the emergency department, in the context of the prospective EMVERT trial (EMergency VERTigo). All patients received a standardized neuro-otological examination including videooculography and posturography in the acute symptomatic stage and an MRI within 7 days after symptom onset. Diagnostic performance of state-of-the-art scores, such as HINTS (Head Impulse, gaze-evoked Nystagmus, Test of Skew) and ABCD!##!Results!#!Machine-learning methods (e.g., MultiGMC) outperform univariate scores, such as HINTS or ABCD!##!Conclusions!#!Established clinical scores (such as HINTS) provide a valuable baseline assessment for stroke detection in acute vestibular syndromes. In addition, machine-learning methods may have the potential to increase sensitivity and selectivity in the establishment of a correct diagnosis

Supplement_for_TOLERATE_manuscript – Supplemental material for Incidence and mitigation of gastrointestinal events in patients with relapsing–remitting multiple sclerosis receiving delayed-release dimethyl fumarate: a German phase IV study (TOLERATE)

<p>Supplemental material, Supplement_for_TOLERATE_manuscript for Incidence and mitigation of gastrointestinal events in patients with relapsing–remitting multiple sclerosis receiving delayed-release dimethyl fumarate: a German phase IV study (TOLERATE) by Ralf Gold, Eugen Schlegel, Birte Elias-Hamp, Christian Albert, Stephan Schmidt, Björn Tackenberg, James Xiao, Tom Schaak and Hans Christian Salmen in Therapeutic Advances in Neurological Disorders</p

Ofatumumab versus Teriflunomide in Multiple Sclerosis

BACKGROUND: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known. METHODS: In two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume. RESULTS: Overall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P<0.001) and 0.10 and 0.25 in trial 2 (difference, -0.15; 95% CI, -0.20 to -0.09; P<0.001). In the pooled trials, the percentage of patients with disability worsening confirmed at 3 months was 10.9% with ofatumumab and 15.0% with teriflunomide (hazard ratio, 0.66; P = 0.002); the percentage with disability worsening confirmed at 6 months was 8.1% and 12.0%, respectively (hazard ratio, 0.68; P = 0.01); and the percentage with disability improvement confirmed at 6 months was 11.0% and 8.1% (hazard ratio, 1.35; P = 0.09). The number of gadolinium-enhancing lesions per T1-weighted MRI scan, the annualized rate of lesions on T2-weighted MRI, and serum neurofilament light chain levels, but not the change in brain volume, were in the same direction as the primary end point. Injection-related reactions occurred in 20.2% in the ofatumumab group and in 15.0% in the teriflunomide group (placebo injections). Serious infections occurred in 2.5% and 1.8% of the patients in the respective groups. CONCLUSIONS: Among patients with multiple sclerosis, ofatumumab was associated with lower annualized relapse rates than teriflunomide. (Funded by Novartis; ASCLEPIOS I and II ClinicalTrials.gov numbers, NCT02792218 and NCT02792231.)