Therapeutic plasma exchange in multiple sclerosis patients with an aggressive relapse: an observational analysis in a high-volume center.

An evidence-based treatment for a Multiple Sclerosis (MS) relapse is an intravenous administration of 3-5 g of Methylprednisolone. In case of insufficient effect or corticosteroids intolerance, the therapeutic plasma exchange (TPE) is indicated. To assess the clinical effect of TPE in treatment of relapse in patients with relapsing-remitting MS (RRMS), we enrolled 155 patients meeting the following criteria (study period: January 2011 to February 2021): (1) age > 18, (2) RRMS according to the McDonald´s 2017 criteria, (3) MS relapse and insufficient effect of corticosteroids/corticosteroids intolerance, (4) baseline EDSS < 8. Exclusion criteria: (1) progressive form of disease, (2) history of previous TPE. Following parameters were monitored: EDSS changes (before and after corticosteroid treatment, before and after TPE; EDSS after TPE was assessed at the next clinical follow-up at the MS Center), and improvement of EDSS according to the number of procedures and baseline severity of relapse. 115 females (74%) and 40 males (26%) were included. The median age was 41 years (IQR 33-47)-131 patients underwent the pulse corticosteroids treatment and TPE, while 24 patients underwent only TPE without any previous corticosteroid treatment. Median baseline EDSS was 4.5 (IQR 3.5-5.5), median EDSS after finishing steroids was 4.5 (IQR 4.0-5.5). EDSS prior to the TPE was 4.5 (IQR 4-6), EDSS after TPE was 4.5 (IQR 3.5-5.5). We observed a significant improvement in the EDSS after TPE (p < 0.001). Sex differences were seen in TPE effectiveness, with median improvement of EDSS in females being -0.5 (IQR 1-0) and in males being 0 (IQR -0.5 to 0), p = 0.048. There was no difference in EDSS improvement by age category: 18-30 years, 31-40 years, 41-50 years, > 50 (p = 0.94), nor by total TPE count (p = 0.91). In this retrospective study of patients with an aggressive relapse and insufficient effect of intravenous corticosteroid treatment, a significant effect of TPE on EDSS improvement was observed. There was no significant difference in TPE effectivity according to the number of procedures, age, nor severity of a relapse. In this cohort, TPE was more effective in females.

Incidence of the urological tumours in patients suffering from multiple sclerosis.

OBJECTIVES: The goal of this study was to evaluate the incidence of urological malignancies in MS patients using active screening. MATERIAL AND METHODS: A total of 495 MS patients (141 men, 354 women, age of 42±13.4) were included in the study. The duration of disease was 12.3±11 years, and the EDSS score was 4.3 (±2.5). Patients, regardless of specific urological symptoms, were referred for urological evaluation. The outcomes of these evaluations were compared with data from the 2009 National Oncology Register of the Czech Republic. RESULTS: The standardized incidence ratio (SIR) for the whole MS study population was 38.8 (95% CI 12.6-90.6). This incidence of urological malignancies in the MS study population was higher (statistically significant) than that of the general population. The SIR for females was 66.0 (95% CI 18.0-169.1) in the MS study population, representing a statistically significant increase over that of the general female population. The increase in incidence of urological malignancies in men with MS did not reach statistical significance over that of the general male population (SIR 14.7, 95% CI 0.4-81.7). CONCLUSIONS: The incidence of urological cancer in MS patients as determined by active screening is significantly higher than that found in general population.

A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols* (Sativex(®) ), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis.

BACKGROUND: Spasticity is a disabling complication of multiple sclerosis, affecting many patients with the condition. We report the first Phase 3 placebo-controlled study of an oral antispasticity agent to use an enriched study design. METHODS: A 19-week follow-up, multicentre, double-blind, randomized, placebo-controlled, parallel-group study in subjects with multiple sclerosis spasticity not fully relieved with current antispasticity therapy. Subjects were treated with nabiximols, as add-on therapy, in a single-blind manner for 4weeks, after which those achieving an improvement in spasticity of ≥20% progressed to a 12-week randomized, placebo-controlled phase. RESULTS: Of the 572 subjects enrolled, 272 achieved a ≥20% improvement after 4weeks of single-blind treatment, and 241 were randomized. The primary end-point was the difference between treatments in the mean spasticity Numeric Rating Scale (NRS) in the randomized, controlled phase of the study. Intention-to-treat (ITT) analysis showed a highly significant difference in favour of nabiximols (P=0.0002). Secondary end-points of responder analysis, Spasm Frequency Score, Sleep Disturbance NRS Patient, Carer and Clinician Global Impression of Change were all significant in favour of nabiximols. CONCLUSIONS: The enriched study design provides a method of determining the efficacy and safety of nabiximols in a way that more closely reflects proposed clinical practice, by limiting exposure to those patients who are likely to benefit from it. Hence, the difference between active and placebo should be a reflection of efficacy and safety in the population intended for treatment.

A double-blind, randomized, placebo-controlled, parallel-group study of Sativex, in subjects with symptoms of spasticity due to multiple sclerosis.

BACKGROUND: Muscle spasticity is common in multiple sclerosis (MS), occurring in more than 60% of patients. OBJECTIVE: To compare Sativex with placebo in relieving symptoms of spasticity due to MS. METHODS: A 15-week, multicenter, double-blind, randomized, placebo-controlled, parallel-group study in 337 subjects with MS spasticity not fully relieved with current anti-spasticity therapy. RESULTS: The primary endpoint was a spasticity 0-10 numeric rating scale (NRS). Intention-to-treat (ITT) analysis showed a non-significant improvement in NRS score, in favor of Sativex. The per protocol (PP) population (79% of subjects) change in NRS score and responder analyses (> or =30% improvement from baseline) were both significantly superior for Sativex, compared with placebo: -1.3 versus -0.8 points (change from baseline, p=0.035); and 36% versus 24% (responders, p=0.040). These were supported by the time to response (ITT: p=0.068; PP: p=0.025) analyses, carer global impression of change assessment (p=0.013) and timed 10-meter walk (p=0.042). Among the subjects who achieved a > or =30% response in spasticity with Sativex, 98, 94 and 73% reported improvements of 10, 20 and 30%, respectively, at least once during the first 4 weeks of treatment. Sativex was generally well tolerated, with most adverse events reported being mild-to-moderate in severity. DISCUSSION AND CONCLUSIONS: The 0-10 NRS and responder PP analyses demonstrated that Sativex treatment resulted in a significant reduction in treatment-resistant spasticity, in subjects with advanced MS and severe spasticity. The response observed within the first 4 weeks of treatment appears to be a useful aid to prediction of responder/non-responder status.

Analysis of the upper urinary tract function in multiple sclerosis patients.

AIMS: The objective of this study was to analyse the upper urinary tract (UT) function in a group of consecutive multiple sclerosis (MS) patients, who had not previously been treated by urologist. MATERIALS AND METHODS: Ninety-two MS patients suffering from lower UT dysfunction were included in the study. The group of patients consisted of 69 women and 23 men. The average Expanded Disability Status Scale (EDSS) score in our group was 4.29 (0-8.5). Functional examination of the kidneys using assessment of creatinine clearance and morphological examination of the kidneys using ultrasound was performed in all patients. Analysis of the upper UT function is presented. RESULTS: The average serum creatinine clearance in our group was 132.84 ml/min/1.73 m(2) (46.8-510). Lower levels than normal were found in three patients (3.3%). Abnormal ultrasound findings were recorded in five patients (5.4%). The creatinine clearance was correlated with the clinical subtype of MS, the severity expressed by EDSS, the urodynamic parameters, the duration of the disease, the duration of the symptoms of lower UT and the EDSS score. We did not find a statistically significant correlation for any of these parameters. CONCLUSIONS: Our results suggest that impairment of the upper UT function is exceptional in MS patients.

[Pregnancy and multiple sclerosis]. / Gravidita a roztrousená skleróza mozkomísní.

OBJECTIVE: To assume the influence of pregnancy on the clinical progress of multiple sclerosis and its influence on the course of delivery. DESIGN: Retrospective analysis. SETTING: Department of Obstetrics and Gynecology, University Hospital in Ostrava, Czech Republic. SUBJECT AND METHOD: It is the retrospective analysis of the influence of pregnancy on the clinical course of multiple sclerosis in the file of 57 patients with diagnosis of multiple sclerosis. The aim of the study is to compare the changes in the EDSS (expanded disability status scale) in the period before the pregnancy, during the pregnancy and 6 months after delivery. The authors also tried to analyze if multiple sclerosis influences the course of delivery. RESULTS: The progression of the multiple sclerosis during pregnancy and postpartum period was present in 62.8% of the patients. The mean change during the pregnancy and 4 months after delivery was 0.7 points in the EDSS scale. We did not find any influence of multiple sclerosis on the course of delivery.