Natalizumab, Fingolimod and Dimethyl Fumarate Use and Pregnancy-Related Relapse and Disability in Women With Multiple Sclerosis

To investigate pregnancy-related disease activity in a contemporary multiple sclerosis (MS) cohort

Country, Sex, EDSS Change and Therapy Choice Independently Predict Treatment Discontinuation in Multiple Sclerosis and Clinically Isolated Syndrome

We conducted a prospective study, MSBASIS, to assess factors leading to first treatment discontinuation in patients with a clinically isolated syndrome (CIS) and early relapsing-remitting multiple sclerosis (RRMS). The MSBASIS Study, conducted by MSBase Study Group members, enrols patients seen from CIS onset, reporting baseline demographics, cerebral magnetic resonance imaging (MRI) features and Expanded Disability Status Scale (EDSS) scores. Follow-up visits report relapses, EDSS scores, and the start and end dates of MS-specific therapies. We performed a multivariable survival analysis to determine factors within this dataset that predict first treatment discontinuation. A total of 2314 CIS patients from 44 centres were followed for a median of 2.7 years, during which time 1247 commenced immunomodulatory drug (IMD) treatment. Ninety percent initiated IMD after a diagnosis of MS was confirmed, and 10% while still in CIS status. Over 40% of these patients stopped their first IMD during the observation period. Females were more likely to cease medication than males (HR 1.36, p = 0.003). Patients treated in Australia were twice as likely to cease their first IMD than patients treated in Spain (HR 1.98, p = 0.001). Increasing EDSS was associated with higher rate of IMD cessation (HR 1.21 per EDSS unit, p<0.001), and intramuscular interferon-β-1a (HR 1.38, p = 0.028) and subcutaneous interferon-β-1a (HR 1.45, p = 0.012) had higher rates of discontinuation than glatiramer acetate, although this varied widely in different countries. Onset cerebral MRI features, age, time to treatment initiation or relapse on treatment were not associated with IMD cessation. In this multivariable survival analysis, female sex, country of residence, EDSS change and IMD choice independently predicted time to first IMD cessation

Real world efficacy and safety of teriflunomide in multiple sclerosis: an observational study with four years follow-up

Background: Efficacy and safety of teriflunomide has been demonstrated in clinical trials, but there is a shortage of data from real-world evidence.Objective: We aimed to describe efficacy, safety and persistence in patients treated with teriflunomide in real-life clinical settings.Methods: Using the Imed MS registry, RRMS patients prescribed teriflunomide in 18 MS centers were retrospectively analyzed. Basic demographics, clinical data, relapses, MRI activities, EDSS scores and discontinuations were recorded as part of routine clinical practice.Results: A total of 1130 RRMS (763 females, 367 males; female/male=2.01) patients treated with teriflunomide were included in the study. Mean age at teriflunomide initiation was 41.3 ± 11.2 years (18-78). Age onset was 30.9 ± 10 (10.4-69.6). Teriflunomide was first line drug in 621 (55%) of the patients. 509 patients switched to teriflunomide from other treatments, 392 (77%) switched from injectable and 49 (9%) from fingolimod, 2 % from natalizumab, 12% from others due to loss of tolerability or inefficacy. The average duration for drug treatment was 16.7 ± 13 months (1 to 80 months). Before treatment, the mean annualized relapse rates (ARR) were 0.63 and the median EDSS was 1.6 (0-5.5). ARR were 0.28 in year 1, 0.24 in year 2, 0.24 in year 3 and 0,20 in year 4. The average time to relapse was 11.2 months. Median EDSS was 1.7 (2.2 ±1.9) in year 1, 2.0 (2.2 ±1.8) in year 2, 2.0 (2.2 ±1.8) and 2.0 (2.6 ±1.9) in year 4. Fifty-three patients had 1 step confirmed EDSS progression. MRI’s showed new or enhanced lesions in 20 % of patients in the first year and % 18 in the second year. 372 patients (%33) discontinued teriflunomide. Discontinuation rates were 13% in year 1 and 24% in year 2. Reported reasons for discontinuations were mainly lack of efficacy, lack of tolerance, adverse events and pregnancy planning. No life-threatened adverse events were encountered.Conclusion: We found that efficacy and safety of teriflunomide in real-life settings were similar to data obtained by the pivotal trials. In this cohort, the female to male ratio were similar to the MS population treated with other drugs. Relapse rates decreased over 4 years of treatment with teriflunomide compared to pre-treatment. We conclude that teriflunomide is a well-tolerated and effective option especially for early RRMS patients as first-line therapy and switch therapy from other medications in patients without high disease activity.</p

Evaluating Treatment Decision for Multiple Sclerosis

PubMedWo

Effects of rituximab on prognosis in myasthenia gravis: A single-center experience from Turkey = A rituximab hatása a myasthenia gravis prognózisára: egy központú, törökországi tapasztalat

Background and purpose – Management of treatmentresistant patients with myasthenia gravis (MG) remains an important issue. This study aimed to evaluate the effects of rituximab (RTX) treatment on the prognosis of patients with acetylcholine receptor autoantibody-positive (AChR-Ab+), muscle-specific kinase autoantibody-positive (MuSK-Ab+), or seronegative or double seropositive MG. Methods – Nineteen patients treated with RTX between 2015 and 2020 were included in this study. Demographic and clinical characteristics, prognosis, and prognostic predictors of MG were evaluated retrospectively. The Myas - thenia Gravis Foundation of America Post-Inter vention Status (MGFA-PIS) before RTX treatment (pre-RTX) and after RTX treatment (post-RTX) were recorded. Results – A total of 10 patients (52.6%) were AchR Ab+, 6 patients (31.6%) were MuSK Ab+, 1 patient (5.3%) was seronegative, and 2 patients (10.5%) were double seropositive. Steroid dose was pre-RTX 38.9±5.7 (25-45), it was post-RTX 10.5±10.3 (0-30) (p<0.001). Post-RTX steroid treatment was discontinued in 6 of 19 patients (p=0.041). Only three patients received intravenous immunoglobulin at the post-RTX follow-up (p<0.001). In post-RTX 12th month, the MGFA-PIS score was as minimally manifestation or better in 9 patients (47.3%) and improved or was better in 18 patients (94.7%) (p-value 0.004; <0.001, respectively). Conclusion – The improvement in MGFA-PIS scores postRTX was similar in MuSK-Ab+ and AChR-Ab+ patients. The data are insufficient in seronegative and double seropositive patients and RTX must be considered in the treatment of suitable patients with MuSK-Ab+ and AChRAb+ refractory MG. = Háttér és cél – A terápiára nem reagáló myasthenia gravis- (MG-) betegek kezelése fontos problémát jelent. Vizsgálatunk célja az volt, hogy megvizsgáljuk a rituxi - mab- (RTX-) kezelés hatását az acetilkolin-receptor-ellenes autoantitest-pozitív (AChR-Ab+), az izomspecifikus kinázellenes autoantitest-pozitív (MuSK-Ab+), a szeronegatív és a dupla szeropozitív MG-ben szenvedô betegek esetében. Módszerek – A vizsgálatba 19 olyan MG-beteget vontunk be, akiket 2015 és 2020 között RTX-szel kezeltek. Retrospektív módon összegyûjtöttük a betegek demográfiai és klinikai adatait, valamint értékeltük az MG prognosztikus prediktorait. Feljegyeztük az RTX-kezelés elôtti (pre-RTX) és utáni (post-RTX) MGFA-PIS-értékeket (MGFAPIS: Myasthenia Gravis Foundation of America PostIntervention Status). Eredmények – 10 beteg (52,6%) volt AChR-Ab+, hat beteg (31,6%) volt MuSK-Ab+, egy beteg (5,3%) volt szeronegatív, és két beteg (10,5%) volt dupla szeropozitív. A pre-RTX szteroiddózis 38,9 ± 5,7 (25–45) volt, a postRTX szteroiddózis pedig 10,5 ± 10,3 (0–30) (p < 0,001). A post-RTX szteroid-kezelés a 19 betegbôl hat esetében vált szükségtelenné (p = 0,041). A post-RTX-utánkövetés során mindössze három beteg kapott intravénás immunglobulint (p < 0,001). Az RTX-kezelés utáni 12. hónapban az MGFA-PIS-pontszám kilenc beteg (47,3%) esetében minimális vagy jobb értékeket mutatott, 18 beteg (94,7%) esetében pedig javuló vagy jobb manifesztációt (p-érték: 0,004; <0,001). Következtetés – Az RTX-kezelés utáni MGFA-PISpontszám-javulás hasonló volt a MuSK-Ab+ és az AChRAb+ betegek körében. A szeronegatív és a dupla szero - pozitív MG-betegek esetében elégtelen mennyiségû adat keletkezett. Az RTX-kezelés megfontolandó a megfelelôen kiválasztott, terápiarezisztens MuSK-Ab+ és AChR-Ab+ MG-betegek esetében

Comparative analysis of fingolimod versus teriflunomide in relapsing-remitting multiple sclerosis

Boz, Cavit/0000-0003-0956-3304; Altintas, Ayse/0000-0002-8524-5087; YUCEYAR, NUR/0000-0003-4590-6423; Sevim, Serhan/0000-0002-0518-3374; Efendi, Husnu/0000-0002-9143-3893WOS: 000502098900008PubMed: 31473488Background: Fingolimod and teriflunomide are commonly used in the treatment of relapsing-remitting multiple sclerosis (RRMS). These have not been compared in controlled trials, but only in observational studies, with inconclusive results. Comparison of their effect on relapse and disability in a real-world setting is therefore needed. Objectives: the objective of this study was to compare the efficacy of fingolimod and teriflunomide in reducing disease activity in RRMS. Methods: This multicenter, retrospective observational study was carried out with prospectively collected data from 15 centers. All consecutive RRMS patients treated with teriflunomide or fingolimod were included. Data for relapses, Expanded Disability Status Scale (EDSS) scores and brain magnetic resonance imaging (MRI) scans were collected. Patients were matched using propensity scores. Annualized relapse rates (ARR), disability accumulation, percentage of patients with active MRI and treatment discontinuation over a median 2.5-year follow-up period were compared. Results: Propensity score matching retained 349 out of 1388 patients in the fingolimod group and 349 out 678 in the teriflunomide group for final analyses. Mean ARR decreased markedly from baseline after 1 and 2 years of treatment in both the fingolimod (0.58-0.17 after 1 year and 0.11 after 2 years, p < 0.001) and teriflunomide (0.56-0.29 after 1 year and 0.31 after 2 years, p < 0.001) groups. Mean ARR was lower in fingolimod-treated patients than in those treated with teriflunomide at years 1 (p = 0.02) and 2 (p = 0.004). Compared to teriflunomide, the fingolimod group exhibited a higher percentage of relapse-free patients and a lower percentage of MRI-active patients after 2.5-year follow-up. Disability worsening was similar between the two groups. Patients were less likely to discontinue fingolimod than teriflunomide (p < 0.001). Conclusion: Fingolimod was associated with a better relapse control and lower discontinuation rate than teriflunomide. the two oral therapies exhibited similar effects on disability outcomes

Historical changes of seasonal differences in the frequency of multiple sclerosis clinical attacks: a multicenter study

Previous papers show discordant patterns of monthly and seasonal differences in the frequency of multiple sclerosis relapses. Attacks are more often reported in spring and summer, but there are many variations, mainly as to summer peaks. This paper, an MSBase collaboration substudy, reports multiple series of relapses from 1980 to 2010, comparing ultradecennal trends of seasonal frequency of attacks in different countries. The MSBase international database was searched for relapses in series recording patient histories from 1980 up to 2010. The number of relapses by month was stratified by decade (1981-1990, 1991-2000, 2001-2010). Positive spring versus summer peaks were compared by odds ratios; different series were compared by weighted odds ratio (Peto OR). Decade comparison of the 1990s versus 2000s shows inversion of spring-summer peak (2000s = March; 1990s = July), significant in the whole group (Peto odds ratio = 1.31, CI = 1.10-1.56, p = 0.003) and in Salerno series (OR = 1.97, CI = 1.14-1.40). The global significance persisted also excluding Salerno series (Peto odds ratio = 1.25, CI = 1.04-1.50, p = 0.002). Multicentric data confirm a summer peak of relapses in the 1991-2000 decade, significantly different from the spring peak of 2001-2010. Seasonal frequency of relapses shows long-term variations, so that other factors such as viral epidemics might have more relevance than ultraviolet exposure

An Outbreak of Botulism: Evaluation of the 24 Patients

Botulism is a neuroparalytic disease caused by the microorganism Clostridium botulinum, which secretes toxins that affect the peripheral synapses. In this study, epidemiological and clinical features of the outbreak of botulism in the Ayvadere village, Trabzon in April 2000 are evaluated and discussed. The material responsible for contamination was identified as home-made cheese, a traditional food in the region. The outbreak affected a total of 24 people of which 16 were men and 8 were women. The mean value of patients age was 39.6 ± 14.9 (16-72) and the mean duration of incubation was 86.5 ± 64 (8-192) hours. The frequency symptoms and signs were as follows; dryness of mouth and fatigue 96%, visual disturbances 83%, dysphagia 79%, decrease in gag reflex 75%, diplopia 63%. The patients were classifed into two groups: Group 1 (n= 11) consisting of patients with generalized symptoms and respiratory distress and Group 2 (n= 13) consisting of patients without respiratory distress symptoms. All patients were followed after hospitalization. In Group 1, 5 patients underwent tracheotomy and of these 4 necessiated mechanical ventilation. Antitoxin was available for only 8 patients in Group 1 and hypersensitivity to antitoxin developed in one patient. Mean duration of stay in hospital in Group 1 was 20.8 ± 15.9 days for those receiving antitoxin (n= 8) and 35 ± 12.1 days for those that did not receive antitoxin. Three patients who died belonged to the Group 1 and were associated with severe respiratory distress. The mean duration of incubation periods for the fatal cases and survived cases was 26.6 ± 20.1 and 95.1 ± 63.7 hours and the patients mean age was 45.6 ± 19.4 and 38.7 ± 14.6 respectively. However no significant difference was present between the groups with respect to incubation (p> 0.05). In the follow-up after three months persistance of complaints such as fatigue and muscular weakness were noted. This is the largest series of botulismus outbreak reported from Turkey, diagnosed in view of clinical and epidemiological features further supported by EMG findings