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

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.

Informations de copyright

Copyright © 2022. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of Competing Interest Helen Tedeholm received a research grant from the Swedish MS Society in 2018. Funds for research time were granted by the Western Swedish Region. Fredrik Piehl has received research grants from Genzyme, Merck KGaA, and UCB, and fees for serving as chair of DMC in clinical trials with Parexel. Jan Lycke has received travel support and/or lecture honoraria from Biogen, Novartis, Merck, Alexion, Roche, and SanofiGenzyme; has served on scientific advisory boards for Biogen, Novartis, Merck, Roche, BSM, and SanofiGenzyme; serves on the editorial board of Acta Neurologica Scandinavica; and has received unconditional research grants from Biogen and Novartis. Jenny Link has nothing to declare. Leszek Stawiarz has nothing to declare. Joachim Burman has nothing to declare. Pierre de Flon has nothing to declare. Katarina Fink has received honoraria for lectures and advisory boards from Merck, Novartis, Roche, Biogen, and Aktelion. Martin Gunnarsson has nothing to declare. Johan Mellergård has received honoraria for advisory boards from Biogen, Sanofi Genzyme and Merck and lecture honoraria from Merck. Petra Nilsson has received travel support from Bayer Schering Pharma, Merck Serono, Biogen, and Genzyme a Sanofi Company; honoraria for lectures and advisory boards from Merck Serono and Genzyme a Sanofi Company; serves on advisory boards for Novartis and Roche; lectures for Biogen; and has received unrestricted grants from Biogen. Peter Sundström has nothing to declare. Anders Svenningsson has nothing to declare. Helena Johansson has nothing to declare. Oluf Andersen serves on the editorial board of Acta Neurologica Scandinavica.