The aim of this work was to evaluate sex differences in the incidence of multiple sclerosis relapses; assess the relationship between sex and primary progressive disease course; and compare effects of age and disease duration on relapse incidence. Annualized relapse rates were calculated using the MSBase registry. Patients with incomplete data or <1 year of follow-up were excluded. Patients with primary progressive multiple sclerosis were only included in the sex ratio analysis. Relapse incidences over 40 years of multiple sclerosis or 70 years of age were compared between females and males with Andersen-Gill and Tweedie models. Female-to-male ratios stratified by annual relapse count were evaluated across disease duration and patient age and compared between relapse-onset and primary progressive multiple sclerosis. The study cohort consisted of 11 570 eligible patients with relapse-onset and 881 patients with primary progressive multiple sclerosis. Among the relapse-onset patients (82 552 patient-years), 48,362 relapses were recorded. Relapse frequency was 17.7% higher in females compared with males. Within the initial 5 years, the female-to-male ratio increased from 2.3:1 to 3.3:1 in patients with 0 versus ≥4 relapses per year, respectively. The magnitude of this sex effect increased at longer disease duration and older age (P < 10(-12)). However, the female-to-male ratio in patients with relapse-onset multiple sclerosis and zero relapses in any given year was double that of the patients with primary progressive multiple sclerosis. Patient age was a more important determinant of decline in relapse incidence than disease duration (P < 10(-12)). Females are predisposed to higher relapse activity than males. However, this difference does not explain the markedly lower female-to-male sex ratio in primary progressive multiple sclerosis. Decline in relapse activity over time is more closely related to patient age than disease duration.
This study demonstrated that both low-dose topiramate and propranolol could significantly reduce migraine headache frequency, intensity, and duration. However, compared with propranolol, low-dose topiramate showed better results.
Background and Objectives:The severity of multiple sclerosis (MS) varies widely among individuals. Understanding the determinants of this heterogeneity will help clinicians optimize the management of MS. The aim of this study was to investigate the association between latitude of residence, ultraviolet B radiation exposure (UVB) and the severity of MS.Methods:This observational study used the MSBase registry data. The included patients met the 2005 or 2010 McDonald diagnostic criteria for MS and had a minimum dataset recorded in the registry (date of birth, sex, clinic location, date of MS symptom onset, disease phenotype at baseline and censoring, and ≥1 EDSS [Expanded Disability Status Scale] score recorded). The latitude of each study center and cumulative annualized UVB dose at study center (calculated from NASAʼs Total Ozone Mapping Spectrometer) at ages 6 and 18 and the year of disability assessment were calculated. Disease severity was quantified with MS Severity Score (MSSS). Quadratic regression was used to model the associations between latitude, UVB and MSSS.Results:46,128 patients contributing 453,208 visits and a cumulative follow-up of 351,196 patient-years (70% women, mean age 39.2±12, resident between latitudes 19°35´ and 56°16´) were included in this study. Latitude showed a non-linear association with MS severity. In latitudes greater than 40°, more severe disease was associated with higher latitudes (β=0.08, 95%CI: 0.04 to 0.12). For example, this translates into a mean difference of 1.3 points of MSSS between patients living in Madrid and Copenhagen. No such association was observed in latitudes <40° (β=-0.02, 95% CI:-0.06 to 0.03). The overall disability accrual was faster in those with a lower level of estimated UVB exposure before the age of 6 (β=- 0.5, 95% CI: -0.6 to 0.4) and 18 years (β=- 0.6, 95%CI:-0.7 to 0.4), as well as with lower life-time UVB exposure at the time of disability assessment (β=-1.0, 95%CI:-1.1 to 0.9).Discussion:In temperate zones, MS severity is associated with latitude. This association is mainly, but not exclusively, driven by UVB exposure contributing to both MS susceptibility and severity.
Background: Natalizumab and fingolimod were the first preparations recommended for disease breakthrough in priorly treated relapsing-remitting multiple sclerosis. Of three published head-to-head studies two showed that natalizumab is the more effective to prevent relapses and EDSS worsening. Methods: By re-analyzing original published results from MSBase, France, and Denmark using uniform methodologies, we aimed at identifying the effects of differences in methodology, in the MS-populations, and at reevaluating the differences in effectiveness between the two drugs. We gained access to copies of the individual amended databases and pooled all data. We used uniform inclusion/ exclusion criteria and statistical methods with Inverse Probability Treatment Weighting. Results: The pooled analyses comprised 968 natalizumab-and 1479 fingolimod treated patients. The ontreatment natalizumab/fingolimod relapse rate ratio was 0.77 (p=0.004). The hazard ratio (HR) for a first relapse was 0.82 (p=0.030), and the HR for sustained EDSS improvement was 1.4 (p=0.009). There were modest differences between each of the original published studies and the replication study, but the conclusions of the three original studies remained unchanged: in two of them natalizumab was more effective, but in the third there was no difference between natalizumab and fingolimod. Conclusion:The results were largely invariant to the epidemiological and statistical methods but differed between the MS populations. Generally, the advantage of natalizumab was confirmed.with the Center for Data Review applications (j. nr. 2012-58-0004/VD-2018-121 I-suite 6361). Declaration of Competing InterestJ.B. Andersen received travel grant and congress participation support from Merck.N. Koch-Henriksen received support for participation in congresses and symposia by Biogen, Merck, Novartis, and Teva.F. Sellebjerg served on scientific advisory boards, been on the steering committees of clinical trials, served as a consultant, received support for congress participation, received speaker honoraria, or received research support for his laboratory from Biogen, Merck, Novartis, Roche, Sanofi Genzyme and Teva. P. S. Sørensen received personal compensation for serving on scientific advisory boards, steering committees, independent data monitoring committees or have received speaker honoraria for Merck, Novartis, TEVA, GlaxoSmithKline, MedDay Pharmaceuticals, SanofiAventis/Genzyme, and Celgene.C. Hilt received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genzyme, Biogen, Roche, Novartis, and Merck P.V. Rasmussen received speaker honoraria from TEVA, Biogen, Roche and Novartis, support for congress participation from Merck, Roche, Sanofi and TEVA, fees for serving on advisory boards from Merck, Roche, Novartis, Biogen, and Sanofi.M.B. Jensen served on scientific advisory boards, served as a consultant, received support for congress participation or received speaker honoraria from Biogen, Merck, Novartis, Roch...
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