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Effectiveness of first generation disease-modifying therapy to prevent conversion to secondary progressive multiple sclerosis

Tedeholm, H. ; Piehl, F. ; Lycke, J. ; Link, J. ; Stawiarz, L. ; Burman, J. ; de Flon, P. ; Fink, K. ; Gunnarsson, M. and Mellergård, J. , et al. (2022) In Multiple Sclerosis and Related Disorders 68.
Abstract

Background: The use of disease-modifying therapies (DMTs) in multiple sclerosis (MS) has been associated with reduced relapse rates and accumulation of disability. However, studies examining impact of DMT on risk of transition to secondary progressive MS (SPMS) leveraging population-based nationwide data are still rare. Here, we determine the population incidence of conversion to SPMS using two consecutive nation-wide cohorts, one immediately before and one after the introduction of DMT in Sweden. Methods: We included two consecutive population cohorts of relapsing-remitting MS (RRMS) from the Swedish national MS register for the periods 1975–1994 (n = 2161), before DMT availability, and 1995–2011 (n = 3510), in which DMTs, mainly first... (More)

Background: The use of disease-modifying therapies (DMTs) in multiple sclerosis (MS) has been associated with reduced relapse rates and accumulation of disability. However, studies examining impact of DMT on risk of transition to secondary progressive MS (SPMS) leveraging population-based nationwide data are still rare. Here, we determine the population incidence of conversion to SPMS using two consecutive nation-wide cohorts, one immediately before and one after the introduction of DMT in Sweden. Methods: We included two consecutive population cohorts of relapsing-remitting MS (RRMS) from the Swedish national MS register for the periods 1975–1994 (n = 2161), before DMT availability, and 1995–2011 (n = 3510), in which DMTs, mainly first generation DMT (injectables), became available and eventually were used by 70% of patients. We explored the risk of transition to SPMS as a calendar year function encompassing the two cohorts. In addition, we determined the incidence of transition to SPMS through age strata below and above 50 years in untreated and treated patient subgroups. Results: The risk of conversion to SPMS (adjusted for current age, current time since onset, calendar year and sex) was significantly lower in the second compared with the first population cohort (hazard ratio 0.58; CI 0.48, 0.70). The risk of SPMS conversion per calendar year decreased by 2.6% annually (p < 0.001) after 1995. The risk of SPMS conversion increased with age until age 50. Thereafter, it was unchanged or decreased among those with early MS onset age (<35 years), but continued to increase with onset at higher age, with similar trends in treated and untreated subgroups. Conclusion: The incidence of SPMS conversion significantly decreased at the population level after introduction of first generation DMTs by 1995. DMT efficiency was confirmed by a downward turn of the annual trajectory of the risk of SPMS conversion after 1995. An onset age determined pattern of variable SPMS incidence in higher age appeared in both treated and untreated strata. While first generation DMT delayed conversion to SPMS, their long-term effect was only moderate.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Annual incidence, Disease-modifying therapy, Multiple sclerosis, Observational study, Secondary progression
in
Multiple Sclerosis and Related Disorders
volume
68
article number
104220
publisher
Elsevier
external identifiers
  • scopus:85139846258
  • pmid:36242804
ISSN
2211-0348
DOI
10.1016/j.msard.2022.104220
language
English
LU publication?
yes
id
e0481bba-bdc4-4537-9ca5-20f04d7aecbc
date added to LUP
2022-12-13 10:36:20
date last changed
2024-06-13 21:30:23
@article{e0481bba-bdc4-4537-9ca5-20f04d7aecbc,
  abstract     = {{<p>Background: The use of disease-modifying therapies (DMTs) in multiple sclerosis (MS) has been associated with reduced relapse rates and accumulation of disability. However, studies examining impact of DMT on risk of transition to secondary progressive MS (SPMS) leveraging population-based nationwide data are still rare. Here, we determine the population incidence of conversion to SPMS using two consecutive nation-wide cohorts, one immediately before and one after the introduction of DMT in Sweden. Methods: We included two consecutive population cohorts of relapsing-remitting MS (RRMS) from the Swedish national MS register for the periods 1975–1994 (n = 2161), before DMT availability, and 1995–2011 (n = 3510), in which DMTs, mainly first generation DMT (injectables), became available and eventually were used by 70% of patients. We explored the risk of transition to SPMS as a calendar year function encompassing the two cohorts. In addition, we determined the incidence of transition to SPMS through age strata below and above 50 years in untreated and treated patient subgroups. Results: The risk of conversion to SPMS (adjusted for current age, current time since onset, calendar year and sex) was significantly lower in the second compared with the first population cohort (hazard ratio 0.58; CI 0.48, 0.70). The risk of SPMS conversion per calendar year decreased by 2.6% annually (p &lt; 0.001) after 1995. The risk of SPMS conversion increased with age until age 50. Thereafter, it was unchanged or decreased among those with early MS onset age (&lt;35 years), but continued to increase with onset at higher age, with similar trends in treated and untreated subgroups. Conclusion: The incidence of SPMS conversion significantly decreased at the population level after introduction of first generation DMTs by 1995. DMT efficiency was confirmed by a downward turn of the annual trajectory of the risk of SPMS conversion after 1995. An onset age determined pattern of variable SPMS incidence in higher age appeared in both treated and untreated strata. While first generation DMT delayed conversion to SPMS, their long-term effect was only moderate.</p>}},
  author       = {{Tedeholm, H. and Piehl, F. and Lycke, J. and Link, J. and Stawiarz, L. and Burman, J. and de Flon, P. and Fink, K. and Gunnarsson, M. and Mellergård, J. and Nilsson, P. and Sundström, P. and Svenningsson, A. and Johansson, H. and Andersen, O.}},
  issn         = {{2211-0348}},
  keywords     = {{Annual incidence; Disease-modifying therapy; Multiple sclerosis; Observational study; Secondary progression}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Multiple Sclerosis and Related Disorders}},
  title        = {{Effectiveness of first generation disease-modifying therapy to prevent conversion to secondary progressive multiple sclerosis}},
  url          = {{http://dx.doi.org/10.1016/j.msard.2022.104220}},
  doi          = {{10.1016/j.msard.2022.104220}},
  volume       = {{68}},
  year         = {{2022}},
}