Multiple sclerosis in Latin America: A different disease course severity? A collaborative study from the MSBase Registry

Limited data suggest that multiple sclerosis (MS) in Latin America (LA) could be less severe than in the rest of the world. The objective was to compare the course of MS between LA and other regions. Methods: Centers from 18 countries with >20 cases enrolled in the MSBase Registry participated. Patients with MS with a disease duration of >1 year and <30 years at time of EDSS measurement were evaluated. The MS Severity Score (MSSS) was used as a measure of disease progression. Comparisons among regions (North America, Europe, Australia and LA), hemispheres and countries were performed. Results: A total of 9610 patients were included. Patients were from: Europe, 6290 (65.6%); North America, 1609 (16.7%); Australia, 1119 (11.6%); and LA, 592 (6.1%). The mean MSSS in patients from LA was 4.47±2.8, 4.53±2.8 in North America, 4.51±2.8 in Europe and 4.49±2.7 in Australia. Mean MSSS in the northern hemisphere was 4.51±1.6 compared to 4.48±1.9 in the southern hemisphere. No differences were found for MSSS among hemispheres (p ¼ 0.68), regions (p ¼ 0.96) or countries (p ¼ 0.50). Conclusions: Our analyses did not discover any difference in mean MSSS among patients from different regions, hemispheres or countries

Seasonal variation of relapse rate in multiple sclerosis is latitude dependent

Objective: Previous studies assessing seasonal variation of relapse onset in multiple sclerosis have had conflicting results. Small relapse numbers, differing diagnostic criteria, and single region studies limit the generalizability of prior results. The aim of this study was to determine whether there is a temporal variation in onset of relapses in both hemispheres and to determine whether seasonal peak relapse probability varies with latitude. Methods: The international MSBase Registry was utilized to analyze seasonal relapse onset distribution by hemisphere and latitudinal location. All analyses were weighted for the patient number contributed by each center. A sine regression model was used to model relapse onset and ultraviolet radiation (UVR) seasonality. Linear regression was used to investigate associations of latitude and lag between UVR trough and subsequent relapse peak. Results: A total of 32,762 relapses from 9,811 patients across 30 countries were analyzed. Relapse onset followed an annual cyclical sinusoidal pattern with peaks in early spring and troughs in autumn in both hemispheres. Every 10° of latitude away from the equator was associated with a mean decrease in UVR trough to subsequent relapse peak lag of 28.5 days (95% confidence interval = 3.29–53.71, p = 0.028). Interpretation: We demonstrate for the first time that there is a latitude-dependent relationship between seasonal UVR trough and relapse onset probability peak independent of location-specific UVR levels, with more distal latitude associated with shorter gaps. We confirm prior meta-analyses showing a strong seasonal relapse onset probability variation in the northern hemisphere, and extend this observation to the southern hemisphere

Exposure to treatment with interferon β-1a SC thrice weekly.

<p>Numbers of patients treated with Rebif recorded within the MSBase registry (n = 4678) and stratified by time on treatment are shown. Red bar in year 1 indicates the proportion of patients in whom dose escalation was a planned procedure. TIW, three times weekly.</p

Baseline demographic and clinical data in patients unmatched and matched by the propensity score.

<p>CIS, clinical isolated syndrome; EDSS, Expanded Disability Status Scale; MS, multiple sclerosis; PPMS, primary progressive multiple sclerosis; RRMS, relapsing-remitting multiple sclerosis; SD, standard deviation; SPMS, secondary progressive multiple sclerosis.</p

Discontinuation events.

<p>Data are presented as number of discontinuation events with annual probability of discontinuation stratified by recorded reasons for discontinuation. The events were recorded in all patients within the MSBase ever treated with Rebif. Escalations of treatment dosage planned as part of the treatment initiation protocol (i.e. occurring within the initial 6 months of treatment with Rebif 22 µg) were excluded.</p

Baseline demographic, clinical and MRI data in the sub-group with available MRI, unmatched and matched by the propensity score.

<p>CIS, clinical isolated syndrome; EDSS, Expanded Disability Status Scale; MRI, magnetic resonance imaging; MS, multiple sclerosis; PPMS, primary progressive multiple sclerosis; RRMS, relapsing-remitting multiple sclerosis; SD, standard deviation; SPMS, secondary progressive multiple sclerosis.</p

Kaplan-Meier plots for the proportion of patients free from clinical relapses.

<p>No statistically significant differences between the treatment dosages were observed. MRI, magnetic resonance imaging; TIW, three times weekly.</p

Likelihood of discontinuation by exposure to treatment.

<p>Overall proportion of treatment discontinuations in patients treated with either Rebif dosage is shown (left). Discontinuation rates by the recorded reasons are shown. Hazard ratio (HR) is given where significantly different from 1, dashed lines represent 95% confidence intervals. Planned dose escalations within the first year of treatment are not included. HR, hazard ratio; TIW, three times weekly.</p