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

H Tedeholm; F Piehl; J Lycke; J Link; L Stawiarz; J Burman; P de Flon; K Fink; M Gunnarsson; J Mellergård; P Nilsson; P Sundström; A Svenningsson; H Johansson; O Andersen

doi:10.1016/j.msard.2022.104220

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

Mult Scler Relat Disord. 2022 Dec:68:104220. doi: 10.1016/j.msard.2022.104220. Epub 2022 Oct 5.

Authors

H Tedeholm¹, F Piehl², J Lycke¹, J Link³, L Stawiarz³, J Burman⁴, P de Flon⁵, K Fink⁶, M Gunnarsson⁷, J Mellergård⁸, P Nilsson⁹, P Sundström¹⁰, A Svenningsson¹¹, H Johansson¹², O Andersen¹³

Affiliations

¹ Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg. Department of Neurology, Sahlgrenska University Hospital, 413 45 Göteborg, Sweden.
² Neuroimmunology Unit., Department of Clinical Neuroscience, Karolinska Institute, CMM L8:4 Karolinska University Hospital Solna, Stockholm, Sweden.
³ Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
⁴ Department of Neuroscience, Uppsala University, Uppsala, Sweden.
⁵ Unit of Neurology, Östersund Hospital, Östersund, Jämtland Härjedalen Region, Sweden.
⁶ Department of Neurology, Karolinska University Hospital, Stockholm, Sweden, Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
⁷ Department of Neurology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
⁸ Department of Neurology and Department of Biomedical and Clinical Sciences Linköping University, Linköping, Sweden.
⁹ Department of Clinical Sciences, Neurology, Lund University, Skåne University Hospital, Lund, Sweden.
¹⁰ Department of Clinical Science, Neurosciences, Umeå University, Umeå, Sweden.
¹¹ Department of Clinical Sciences, Karolinska Institute, Danderyd Hospital, Stockholm, Sweden.
¹² Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden, and Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, Victoria, Australia.
¹³ Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg. Department of Neurology, Sahlgrenska University Hospital, 413 45 Göteborg, Sweden. Electronic address: Oluf.andersen@neuro.gu.se.

PMID: 36242804
DOI: 10.1016/j.msard.2022.104220

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 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.

Keywords: Annual incidence; Disease-modifying therapy; Multiple sclerosis; Observational study; Secondary progression.

MeSH terms

Adult
Disease Progression
Humans
Incidence
Middle Aged
Multiple Sclerosis*
Multiple Sclerosis, Chronic Progressive* / drug therapy
Multiple Sclerosis, Chronic Progressive* / epidemiology
Multiple Sclerosis, Relapsing-Remitting* / drug therapy
Multiple Sclerosis, Relapsing-Remitting* / epidemiology
Recurrence