Long-term Survival in Multiple Sclerosis is Improving
Stig Wergeland1, Janne Mannseth1, Sari Atula3, Lars Forsberg4, Anna Glaser4, Hanna Joensen5, Melinda Magyari5, Merja Soilu-Hanninen6, Matias Viitala7, Jan Hillert4, Nina Grytten2
1Norwegian MS-registry and biobank, 2National MS competence center, Haukeland University Hospital, 3Neurocenter, Helsinki University Hospital, 4Karolinska Institute, 5Danish Multiple Sclerosis Center and the Danish Multiple Sclerosis Registry, Copenhagen University Hospital, 6Neurocenter, Turku University Hospital, 7StellarQ Ltd
Objective:

To study longitudinal survival probability by period of MS-diagnosis and time from disease onset to diagnosis using nation-wide data from the Nordic MS-registries.

Background:
Long-term studies evaluating benefit from disease modifying therapy are few and the data on effects of treatment on survival in MS are limited. 
Design/Methods:

All patients in the MS registries in Norway (N=11869), Sweden (N=20696), Denmark (N=21492) and Finland (N=17716) alive at the study starting point of Jan 1st 2000 were included in the study, with a follow-up time for up to 20 years. A total of 6333 deaths were recorded during the follow-up period ending Dec. 31st 2020. Long-term survival in MS patients was analyzed in each MS-registry cohort using Cox proportional hazards regression. Covariates included in the regression model were sex (ref:male), age at onset, calendar period of diagnosis (< 1980, 1981-1989, 1990-1999 (ref), >1999), MS phenotype at diagnosis (relapsing-remitting MS (ref), primary progressive MS) and diagnostic delay (time from MS onset to MS diagnosis in years: <2 (ref), 2-4, 5-10, > 10). Results were then combined and used in meta-analyses to identify common effects or variations as well as overall estimates using all four MS registries.

Results:

The overall estimated values for hazard ratios and 95% confidence intervals for sex were 0.66 [0.61, 0.71], for onset age 1.06 [1.05, 1.07], for MS phenotype 1.65 [1.44, 1.89], for period of diagnosis 4.95 [2.44, 10.07], 2.03 [1.49, 2.76], 0.48 [0.35, 0.65], and for diagnostic delay 1.37 [1.23, 1.52], 1.70 [1.55, 1.86], 3.52 [3.09, 4.00]. The estimated effects were all significant, while the test for heterogeneity was significant for diagnosis period and diagnostic delay.

Conclusions:
In this study based on four nation-wise population-based Nordic MS-registries , we found that survival in MS has improved significantly over time depending on period of MS diagnosis, and that diagnostic delay significantly reduces survival probability.
10.1212/WNL.0000000000202149