Developing medicines for the pre-symptomatic stage of degenerative neurological conditions: Challenges and opportunities.

Neurodegenerative disorders have a devastating disease course and an increasing prevalence due to prolonged life expectancy. In the last decades, it has become increasingly clear that these diseases often start much earlier, before the onset of symptoms, creating a potential window for pre-symptomatic treatment, a strategy that is desirable from both the biologic and the ethical point of view. However, studying treatments for a pre-symptomatic population presents objective difficulties. This article intends to give a perspective about opportunities and challenges of pre-symptomatic prevention of neurodegenerative diseases. Besides the requirement for biomarkers that would facilitate both the selection of study population and demonstrating a treatment effect, further considerations about balancing benefits, risks and uncertainties pertaining a pre-symptomatic population will be examined.

Symptomatic Care in Multiple System Atrophy: State of the Art.

Without any disease-modifying treatment strategy for multiple system atrophy (MSA), the therapeutic management of MSA patients focuses on a multidisciplinary strategy of symptom control. In the present review, we will focus on state of the art treatment in MSA and additionally give a short overview about ongoing randomized controlled trials in this field.

Developing evidence-based guidelines for the safety of symptomatic drugs in multiple sclerosis during pregnancy and breastfeeding: A systematic review and Delphi consensus.

BACKGROUND: Multiple sclerosis (MS) is frequently diagnosed in people of reproductive age, many of whom will become pregnant following diagnosis. Although many women report an improvement in symptoms and relapses during pregnancy, symptoms such as fatigue and spasticity are commonly reported and can worsen. Prescribing medications during pregnancy and breastfeeding presents unique challenges and guidance on the use of symptomatic therapies is limited. OBJECTIVES: This paper aims to provide a consensus on the current evidence base to facilitate informed decision-making and optimise pre-conception counselling. METHODS: A list of most commonly prescribed medications for symptom management in MS was created using pregnancy and MS-related READ codes in the Welsh GP Dataset, followed by a review by MS neurologists. RESULTS: A final list of 24 medications was generated for review. Searches were performed on each medication, and evidence graded using standardised criteria. Evidence-based recommendations were developed and distributed to experts in the field and revised according to feedback using modified Delphi criteria. CONCLUSIONS: Our guidelines provide evidence-based recommendations on the safety of symptomatic therapies during pregnancy and breastfeeding for general practitioners and specialist teams working with people with MS who are hoping to embark on pregnancy or are currently pregnant. Individual risk-benefit ratios should be considered during pre-conception counselling to optimise symptom burden and minimise harm to both parent and child.

Intravesical injections of botulinum neurotoxin A to treat overactive bladder and/or detrusor overactivity related to multiple sclerosis: 5-Year continuation rate and specific risk factors for discontinuation-A study from the neuro-urology committee of the French Association of Urology.

BACKGROUND: While intravesical injections of botulinum neurotoxin A (BoNT-A) are currently recommended for patients experiencing refractory neurogenic overactive bladder and/or detrusor overactivity (OAB/DO), it is unclear how much this therapy is effective and sustainable in the long-term in patients with multiple sclerosis (MS). OBJECTIVES: To assess the mid-term continuation rate of BoNT-A injections to treat neurogenic OAB/DO in MS patients and to investigate MS-specific risk factors for discontinuation. METHODS: This retrospective study involved 11 French university hospital centers. All MS patients who received BoNT-A to treat neurogenic OAB/DO between 2008 and 2013 and were subsequently followed up for at least 5 years were eligible. RESULTS: Of the 196 MS patients included, 159 (81.1%) were still under BoNT-A 5 years after the first injection. The combination of the Expanded Disability Status Scale (EDSS < 6 or ⩾ 6) and of the MS type (relapsing-remitting vs progressive) predicted the risk of discontinuation. This risk was 5.5% for patients with no risk factor, whereas patients presenting with one or two risk factors were 3.3 and 5.7 times more likely to discontinue, respectively. CONCLUSION: BoNT-A is a satisfying mid-term neurogenic OAB/DO therapy for most MS patients. Combining EDSS and MS type could help predict BoNT-A discontinuation.

Parkinson's disease therapy: what lies ahead?

The worldwide prevalence of Parkinson's disease (PD) has been constantly increasing in the last decades. With rising life expectancy, a longer disease duration in PD patients is observed, further increasing the need and socioeconomic importance of adequate PD treatment. Today, PD is exclusively treated symptomatically, mainly by dopaminergic stimulation, while efforts to modify disease progression could not yet be translated to the clinics. New formulations of approved drugs and treatment options of motor fluctuations in advanced stages accompanied by telehealth monitoring have improved PD patients care. In addition, continuous improvement in the understanding of PD disease mechanisms resulted in the identification of new pharmacological targets. Applying novel trial designs, targeting of pre-symptomatic disease stages, and the acknowledgment of PD heterogeneity raise hopes to overcome past failures in the development of drugs for disease modification. In this review, we address these recent developments and venture a glimpse into the future of PD therapy in the years to come.

Patterns of use of symptomatic treatments for Alzheimer's disease dementia (AD).

BACKGROUND: Symptomatic treatment for Alzheimer's disease (AD) dementia could temporarily slow symptom worsening and improve the quality of life for both AD dementia patients and their caregivers. A comprehensive evaluation of symptomatic treatment patterns using recent data for newly diagnosed AD dementia has not been performed and compared across different countries. METHODS: The drug name, time to the first therapy, duration, discontinuation or switches were described in newly diagnosed AD dementia patients in two databases (a major U.S. health plan [US] and UK-Clinical Practice Research Datalink [CPRD GOLD]). This analysis included patients with newly diagnosed AD dementia in 2018-2019, who initiated symptomatic AD drug therapy, with ≥ 1 year baseline period and ≥ 1 year of follow-up. RESULTS: Over median follow-ups of 698 and 645 days, 63% and 65% of AD dementia patients used symptomatic treatments, with 34% and 77% newly initiating therapy, constituting analytic samples of 7637 patients in the US database and 4470 patients in the CPRD, respectively. The median time to the first therapy was 14 days for US and 49 days for CPRD; donepezil ranked the as most frequently used (69% vs 61%), followed by memantine (19% vs 28%) in the US database and CPRD, respectively. Median time on first therapy was 213 and 334 days, and 30% and 12% of patients proceeded to a second treatment in the US and CPRD databases, respectively. CONCLUSION: Approximately two thirds of newly diagnosed AD dementia patients utilized approved symptomatic treatment. Time on first therapy was relatively short (< 1 year) and the majority did not move to a second therapy, highlighting the need for better adherence and persistence to existing AD symptomatic therapies and the need for additional therapies to alleviate the significant burden of AD dementia.

Polypharmacy in Multiple Sclerosis: Prevalence, Risks, and Mitigation Strategies.

PURPOSE OF REVIEW: Polypharmacy, the use of ≥ 5 medications, is common in people with multiple sclerosis and is associated with negative outcomes. The use of multiple medications is common for symptom management in people with multiple sclerosis, but risks drug-drug interactions and additive side effects. Multiple sclerosis providers should therefore focus on the appropriateness and risks versus benefits of pharmacotherapy in each patient. This review describes the prevalence and risks associated with polypharmacy in people with multiple sclerosis and offers strategies to identify and mitigate inappropriate polypharmacy. RECENT FINDINGS: Research in people with multiple sclerosis has identified risk factors and negative outcomes associated with polypharmacy. Medication class-specific investigations highlight their contribution to potentially inappropriate polypharmacy in people with multiple sclerosis. People with multiple sclerosis are at risk for inappropriate polypharmacy. Multiple sclerosis providers should review medications and consider their appropriateness and potential for deprescribing within the context of each patient.

Clinical and financial outcomes of per-oral endoscopic myotomy compared to laparoscopic heller myotomy for treatment of achalasia.

BACKGROUND: Previous studies analyzing short-term outcomes for per-oral endoscopic myotomy (POEM) have shown excellent clinical response rates and shorter operative times compared to laparoscopic Heller myotomy (LHM). Despite this, many payors have been slow to recognize POEM as a valid treatment option. Furthermore, comparative studies analyzing long-term outcomes are limited. This study compares perioperative and long-term outcomes, cost-effectiveness, and reimbursement for POEM and LHM at a single institution. METHODS: Adult patients who underwent POEM or LHM between 2014 and 2021 and had complete preoperative data with at least one complete follow up, were retrospectively analyzed. Demographic data, success rate, operative time, myotomy length, length of stay, pre- and postoperative symptom scores, anti-reflux medication use, cost and reimbursement were compared. RESULTS: 58 patients met inclusion with 25 undergoing LHM and 33 undergoing POEM. There were no significant differences in preoperative characteristics. Treatment success (Eckardt ≤ 3) for POEM and LHM was achieved by 88% and 76% of patients, respectively (p = 0.302). POEM patients had a shorter median operative time (106 min. vs. 145 min., p = 0.003) and longer median myotomy length (11 cm vs. 8 cm, p < 0.001). All LHM patients had a length of stay (LOS) ≥ 1 day vs. 51.5% for POEM patients (p < 0.001). Both groups showed improvements in dysphagia, heartburn, regurgitation, Eckardt score, GERD HRQL, RSI, and anti-reflux medication use. The improvement in dysphagia score was greater in patients undergoing POEM (2.30 vs 1.12, p = 0.003). Median hospital reimbursement was dramatically less for POEM ($3,658 vs. $14,152, p = 0.002), despite median hospital costs being significantly lower compared to LHM ($2,420 vs. $3,132, p = 0.029). RESULTS: POEM is associated with a shorter operative time and LOS, longer myotomy length, and greater resolution of dysphagia compared to LHM. POEM costs are significantly less than LHM but is poorly reimbursed.

Cell-penetrating peptide-conjugated Morpholino rescues SMA in a symptomatic preclinical model.

Spinal muscular atrophy (SMA) is a motor neuron disease and the leading genetic cause of infant mortality. Recently approved SMA therapies have transformed a deadly disease into a survivable one, but these compounds show a wide spectrum of clinical response and effective rescue only in the early stages of the disease. Therefore, safe, symptomatic-suitable, non-invasive treatments with high clinical impact across different phenotypes are urgently needed. We conjugated antisense oligonucleotides with Morpholino (MO) chemistry, which increase SMN protein levels, to cell-penetrating peptides (CPPs) for better cellular distribution. Systemically administered MOs linked to r6 and (RXRRBR)2XB peptides crossed the blood-brain barrier and increased SMN protein levels remarkably, causing striking improvement of survival, neuromuscular function, and neuropathology, even in symptomatic SMA animals. Our study demonstrates that MO-CPP conjugates can significantly expand the therapeutic window through minimally invasive systemic administration, opening the path for clinical applications of this strategy.

Results of a Web-Based Survey on 2105 Greek Migraine Patients-Second Part: Efficacy of Acute and Prophylactic Migraine Treatments and Corresponding Patients' Reported Satisfaction.

Background and Objectives: The Greek Society of Migraine and Headache Patients conducted, in 2020, its second online survey, titled "Migraine in Greece-2020", after publication of the first similar online survey conducted in 2018. To compare the current findings with the corresponding data obtained in 2018, we herein release the second part of results obtained from the 2020 survey on the efficacy of preventive and symptomatic anti-migraine medications and the patients' reported satisfaction with these treatments. Materials and Methods: We surveyed 2105 migraine patients from all over Greece with the use of a 151-questions specific migraine-focused questionnaire in Greek language, which was distributed through the online research software "SurveyMonkey". Results: Triptans were mostly used with efficacy for the symptomatic relief of migraine attacks. About 2 of 3 surveyed patients had received various prophylactic oral medications and the majority of them discontinued these prophylactic medications as a result of inefficacy/safety issues. BoNTA was reported to be effective only when administration was commenced by a trained neurologist/headache specialist, while our current findings are generally comparable to those obtained in our 2018 pre-COVID-19 survey and the pandemic has not imposed any significant attitudes on migraine therapies and corresponding patients' satisfaction. Conclusion: Although a market change is anticipated with the evolving widespread use of anti-CGRPs monoclonal antibodies or gepants in the symptomatic and prophylactic treatment of migraine, it is of great interest to review published results of larger longitudinal population-based studies to further ascertain the satisfaction of patients to migraine therapies.

Development of recommendations for the use of venoactive drugs in the treatment of chronic venous disease - where they are effective and where they are not.

The article provides an overview of the development of recommendations for indications of venoactive drugs for treating symptoms and signs associated with chronic venous disease (CVD). Venoactive drugs may be beneficial in patients with subjective problems and/or swelling of the lower limbs, after surgery for varicose veins, in chronic venous insufficiency or in microcirculatory disorders. They are not indicated in asymptomatic patients with CVD, in the prevention of varicose veins or to prevent their progression. Drugs with proven efficacy in clinical trials should be preferred.

Fluoxetine for the Symptomatic Treatment of Multiple System Atrophy: The MSA-FLUO Trial.

BACKGROUND: There are no effective treatments for multiple system atrophy (MSA). OBJECTIVE: The objective of this study was to assess the efficacy and safety of the serotonin reuptake inhibitor fluoxetine (40 mg/d) for the symptomatic treatment of MSA. METHODS: This was a double-blind, parallel-group, placebo-controlled, randomized trial in patients with "probable" MSA. The primary outcome was the change from baseline to week 12 in the mean total score of the Unified MSA Rating Scale (UMSARS Parts I + II). Secondary outcomes included change from baseline to week 6 in total UMSARS, and change from baseline to week 12 in the Scales for Outcomes in Parkinson Disease-Autonomic Dysfunction, Beck Depression Inventory, and different domains of the MSA-Quality of Life Questionnaire. Exploratory outcomes included change from baseline to week 12 in the UMSARS Parts I and II separately and change from baseline to week 24 in the total UMSARS score. RESULTS: A total of 81 patients were randomly assigned, with no significant difference in the primary outcome (-2.13 units [95% confidence interval, CI, -4.55 to 0.29]; P = 0.08). There was a greater reduction on fluoxetine in the change from baseline to 12-week in UMSARS Part II (exploratory outcome: -1.41 units [95% CI, -2.84; 0.03]; p = 0.05) and in MSA-QoL emotional/social dimension (secondary outcome: -6.99 units [95% CI, -13.40; -0.56]; p < 0.03). A total of 5 deaths occurred (3 on fluoxetine and 2 on placebo). CONCLUSION: The MSA-FLUO failed to demonstrate fluoxetine superiority over placebo on the total UMSARS score, whereas trends in motor and emotional secondary/exploratory outcomes deserve further investigation. © 2021 International Parkinson and Movement Disorder Society.

Myasthenia Gravis in Poland: National Healthcare Database Epidemiological Study.

INTRODUCTION: Myasthenia gravis (MG) is a rare autoimmune disorder of the neuromuscular junction. MG epidemiology has not been studied in Poland in a nationwide study before. METHODS: Our epidemiological data were drawn from the National Health Fund (Narodowy Fundusz Zdrowia, NFZ) database; an MG patient was defined as a person who received at least once medical service coded in ICD-10 as MG (G70) and at least 2 reimbursed prescriptions for pyridostigmine bromide (Mestinon®) or ambenonium chloride (Mytelase®) in 2 consecutive years. RESULTS: On 1st of January 2019, 8,702 patients with MG were receiving symptomatic treatment (female:male ratio: 1.65:1). MG incidence was 2.36/100,000. The mean age of incident cases in 2018 was 61.37 years, 59.17 years for women and 64.12 years for men. Incidence of early-onset MG (<50 years) was 0.80/100,000 and 4.98/100,000 for late-onset MG (LOMG), with male predominance in LOMG. Prevalence was 22.65/100,000. In women, there was a constant increase in prevalence of symptomatic MG from the first decade of life up to 80-89 years. In men, an increase in prevalence appeared in the 6th decade. The highest prevalence was observed in the age group of 80-89 years: 59.65/100,000 in women and 96.25/100,000 in men. CONCLUSIONS: Our findings provide information on epidemiology of MG in Poland and can serve as a tool to evaluate healthcare resources needed for MG patients.

Cortico-subcortical functional connectivity modifications in fatigued multiple sclerosis patients treated with fampridine and amantadine.

BACKGROUND AND PURPOSE: Fatigue in multiple sclerosis (MS) is common and disabling; medication efficacy is still not fully proven. The aim of this study was to investigate 4-week modifications of fatigue severity in 45 relapsing-remitting MS patients after different symptomatic treatments, and changes in concomitant resting state (RS) functional connectivity (FC). METHODS: Patients were randomly, blindly assigned to treatment with fampridine (n = 15), amantadine (n = 15) or placebo (n = 15), and underwent clinical assessment and 3-Tesla RS functional magnetic resonance imaging at baseline (t0) and after 4 weeks (w4) of treatment. Fifteen healthy controls (HCs) were also studied. Changes in modified fatigue impact scale (MFIS) score and network RS FC were assessed. RESULTS: In MS, abnormalities of network RS FC at t0 did not differ between treatment groups and correlated with fatigue severity. At w4, global scores and subscores on the MFIS decreased in all groups, with no time-by-treatment interaction. At w4, all patient groups had changes in RS FC in several networks, with significant time-by-treatment interactions in basal ganglia, sensorimotor and default-mode networks in fampridine-treated patients versus the other groups, and in frontoparietal network in amantadine-treated patients. In the fampridine group, RS FC changes correlated with concurrently decreased MFIS score (r range = -0.75 to 0.74, p range = 0.003-0.05). CONCLUSIONS: Fatigue improved in all MS groups, independently of treatment. Concomitant RS FC modifications were located in sensorimotor, inferior frontal and subcortical regions for fampridine- and amantadine-treated patients, and in associative sensory cortices for placebo-treated patients.

Symptomatic treatment (using NSAIDS) versus antibiotics in uncomplicated lower urinary tract infection: a meta-analysis and systematic review of randomized controlled trials.

BACKGROUND: Current guidelines recommend empiric antibiotics as first-line treatment for uncomplicated UTI. Despite proven benefits in treatment, antibiotic resistance rates remain on the rise. This meta-analysis aims to determine whether non-steroidal anti-inflammatory drugs can serve as an effective and safe option in the treatment of uncomplicated lower UTI among non-pregnant women compared to antibiotics. METHODS: A systematic literature search in PUBMED, CENTRAL, and ACP databases from inception to April 2021 was conducted to identify randomized controlled trials that compare the use of non-steroidal anti-inflammatory drugs versus antibiotics in non-pregnant women ≥18 years old with uncomplicated lower urinary tract infection. Primary outcomes were symptom resolution of UTI by Day 3 or 4 of intervention, and upper UTI complications. Secondary outcomes include persistence of positive urine culture despite treatment and need for another rescue antibiotic. Random and fixed-effects model for dichotomous data using Mantel-Haenszel and Peto odds method were reported at 95% CI followed by sensitivity analysis for substantial heterogeneity. RESULTS: Four RCTs involving 1165 patients were analyzed. The probability of having a symptom resolution by Day 3 or 4 with NSAID use is only less than three-fourths of that with antibiotic treatment (RR: 0.69, 95% CIs [0.55, 0.86], p = 0.0008, I2 = 73%, moderate certainty of evidence). The odds of developing upper UTI complications with use of NSAIDs are 6.49 to 1 for antibiotics (Peto OR: 6.49, 95% CIs [3.02, 13.92], p < 0.00001, I2 = 0%, moderate certainty of evidence). Secondary analysis showed that the NSAID group is 2.77x more likely to have persistence of a positive microbiologic urine culture than the antibiotic group (RR: 2.77, 95% CIs [1.95, 3.94], p < 0.00001, I2 = 36%, moderate certainty of evidence). Treatment with NSAIDs are three times more likely to use a secondary or rescue antibiotic due to persistent or worsening symptoms as compared to antibiotics (RR: 3.16, 95% CIs [2.24, 4.44], p < 0.00001, I2 = 47%, low certainty of evidence). CONCLUSION: Antibiotic treatment was more effective than use of non-steroidal anti-inflammatory drugs for acute uncomplicated lower urinary tract infection with an overall moderate certainty of evidence.

The Clinician's Interview-Based Impression of Change (Plus caregiver input) and goal attainment in two dementia drug trials: Clinical meaningfulness and the initial treatment response.

INTRODUCTION: The Clinician's Interview-Based Impression of Change Plus caregiver input (CIBIC-Plus) has been widely used in dementia drug trials to evaluate cognition, behavior, and function. New trials of symptomatic drugs forecast renewed interest in this measure. METHODS: To test its clinical meaningfulness, we examined how CIBIC-Plus performed in two cholinesterase inhibitor trials compared to goal attainment scaling Scale (GAS) scores, a patient-reported outcome measure. RESULTS: Net goal attainment was seen for all but one GAS domains in subjects who improved on the CIBIC-Plus. Subjects who improved initially on CIBIC-Plus scores were likely to remain improved across all other outcomes for each trial's duration, except for Disability Assessment for Dementia scores. DISCUSSION: The initial response to treatment, as assessed by CIBIC-Plus, remained stable for most outcome measures. Even small CIBIC-Plus improvement changes are associated with clinically meaningful change as assessed by GAS. Other tests detect decline better than improvement.

[Treatment of antibody-mediated encephalomyelitis : Strategies for the treatment of neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody-associated disease]. / Therapie antikörpervermittelter Enzephalomyelitiden : Strategien zur Behandlung der Neuromyelitis-optica-Spektrumerkrankung und der Myelooligodendrozytenglykoprotein-Antikörper-assoziierten Erkrankung.

BACKGROUND: Antibody-mediated encephalomyelitis, such as neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and glial fibrillary acidic protein (GFAP) antibody-associated astrocytopathy belong to a group of newly described autoimmune diseases. AIM: Presentation of the treatment of antibody-mediated encephalomyelitis with a focus on NMOSD and MOGAD. METHODS: Selective literature search in PubMed taking the consultation version of the S2k guidelines of the German Society of Neurology (DGN) on the diagnosis and treatment of multiple sclerosis (MS), NMOSD and MOG IgG-associated diseases into account. RESULTS: Acute relapses are treated with high-dose steroid pulse therapy or apheresis therapy (plasma exchange or immunoadsorption). It is crucial to start treatment as quickly as possible and apheresis therapy can also be used as first-line treatment under certain conditions. For prophylactic immunotherapy, steroids, classical immunosuppressants and monoclonal antibodies with specific mechanisms of action are used. Eculizumab, inebilizumab and satralizumab are the first drugs approved for NMOSD. Symptomatic treatment and neurorehabilitation are important complementary measures. CONCLUSION: Treatment of antibody-mediated encephalomyelitis differs from treatment of multiple sclerosis and requires specific measures.

[The effect of fampridine on gait in people with Multiple sclerosis (MS)].

INTRODUCTION: Fampridine is a drug for people with Multiple Sclerosis (MS). It is a broad-spectrum voltage-dependent potassium channel blocker that enhances synaptic transmission. The drug has been shown to be able to enhance conduction in demyelinated axons, thereby leading to improved gait in patients with MS. The purpose of this study was to examine the effect of fampridine on gait function in people with MS in the end of a 2 weeks trial drug period and to observe how many patients continued drug therapy. MATERIAL AND METHODS: Data from 41 individuals with MS was collected retrospectively for this study. Measurements were administered by physiotherapists and the results from the Timed 25-Foot Walk (T25FW) and 12-item Multiple Sclerosis Walking Scale (MSWS-12) were obtained from medical records from The National University Hospital of Iceland. RESULTS: The results showed a significant difference in walking speed before and at the end of trial period (p<0.0001). The average improvement in walking speed was 22%. Results also demonstrated a significant difference in MSWS-12 scores before and at the end of treatment (p<0.0001). The average improvement in MSWS-12 was 11.4 points. Eighteen individuals (43.9%) continued treatment after the trial period. CONCLUSION: Fampridine can have a positive effect on impaired gait function in people with MS and can be an important adjunct to treatment.

Botulinum toxin for the management of spasticity in multiple sclerosis: the Italian botulinum toxin network study.

BACKGROUND: Botulinum toxin (BT) is an effective and safe treatment for spasticity, with limited evidence in multiple sclerosis (MS). We aim to describe the use of BT for the management of MS spasticity in the clinical practice, its combination with other anti-spastic treatments in MS and possible MS clinical correlates. METHODS: This is a multicentre cross-sectional observational study including 386 MS patients, receiving BT for spasticity in 19 Italian centres (age 53.6 ± 10.9 years; female 228 (59.1%); disease duration 18.7 ± 9.2 years; baseline Expanded Disability Status Scale (EDSS) 6.5 (2.0-9.0)). RESULTS: BT was used for improving mobility (n = 170), functioning in activities of daily living (n = 56), pain (n = 56), posturing-hygiene (n = 63) and daily assistance (n = 41). BT formulations were AbobotulinumtoxinA (n = 138), OnabotulinumtoxinA (n = 133) and IncobotulinumtoxinA (n = 115). After conversion to unified dose units, higher BT dose was associated with higher EDSS (Coeff = 0.591; p < 0.001), higher modified Ashworth scale (Coeff = 0.796; p < 0.001) and non-ambulatory patients (Coeff = 209.382; p = 0.006). Lower BT dose was used in younger patients (Coeff = - 1.746; p = 0.009), with relapsing-remitting MS (Coeff = - 60.371; p = 0.012). BT dose was higher in patients with previous BT injections (Coeff = 5.167; p = 0.001), and with concomitant treatments (Coeff = 43.576; p = 0.022). Three patients (0.7%) reported on post-injection temporary asthenia/weakness (n = 2) and hypophonia (n = 1). CONCLUSION: BT was used for spasticity and its consequences from the early stages of MS, without significant adverse effects. MS-specific goals and injection characteristics can be used to refer MS patients to BT treatment, to decide for the strategy of BT injections and to guide the design of future clinical trials and observational studies.

[Monoclonal antibodies for anti-infective therapy]. / Monoklonale Antikörper zur antiinfektiven Therapie.

Sera of animal origin and hyperimmunoglobulins have dominated serum therapy for a century. Although numerous monoclonal antibodies (MABs) have been developed since the end of the 1980s, particularly for the treatment of immunological and oncological diseases, it will take 20 years before the first anti-infective MAB is approved in the European Union. Interestingly, to combat the COVID-19 pandemic, numerous MABs, which are approved in particular for immunological indications, are currently being used to treat the consequences of SARS-CoV­2 infection, such as pneumonia or hyperimmune reactions.The approved monoclonal antibodies for the treatment of infectious diseases are presented here. In addition, an overview of the current developments, in particular in the treatment of SARS-CoV­2 infection, is provided.