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Multicenter Study
. 2025 May;32(5):e16583.
doi: 10.1111/ene.16583.

Secondary progression activity monitoring in MS despite an early highly active treatment the SPAM study

Mikael Cohen  1 , Fabien Rollot  2   3   4   5 , Marc Debouverie  6 , Hélène Zephir  7 , Sandra Vukusic  2   3   4   5 , Jérome De Seze  8   9 , Pierre Labauge  10   11 , Cassandre Landes-Chateau  1 , Lydiane Mondot  1 , Michael Levraut  1 , Aurélie Ruet  12   13   14 , Eric Berger  15 , David Laplaud  16   17 , Jonathan Ciron  18   19 , Bertrand Bourre  20 , Emmanuelle Le Page  21 , Caroline Papeix  22 , Eric Thouvenot  23   24 , Abdullatif Al Khedr  25 , Bruno Stankoff  26 , Jean Pelletier  27 , Elisabeth Maillart  28 , Olivier Casez  29   30 , Thibault Moreau  31 , Gilles Defer  32 , Pierre Clavelou  33 , Philippe Cabre  34 , Solène Moulin  35 , Jean Philippe Neau  36 , Mickael Zedet  37 , Karolina Hankiewicz  38 , Inès Doghri  39 , Haifa Ben Nasr  40 , Corinne Pottier  41 , Laurent Magy  42 , Dalia Dimitri Boulos  43 , Olivier Heinzlef  44 , Jean Philippe Camdessanche  45 , Marc Coustans  46 , Chantal Nifle  47 , David Brassat  28 , Romain Casey  2   3   4   5 , Christine Lebrun-Frenay  1 ; OFSEP and SFSEP study groups
Affiliations
Multicenter Study

Secondary progression activity monitoring in MS despite an early highly active treatment the SPAM study

Mikael Cohen et al. Eur J Neurol. 2025 May.

Abstract

Background: Real-world data suggest that the early use of highly active therapies (HAT) may reduce the risk of transition to secondary progressive MS (SPMS). However, current knowledge about predictive factors of outcomes needs to be improved. The primary objective of this study was to determine factors associated with the occurrence of SPMS in patients treated early after MS onset with an HAT.

Methods: Retrospective, multicentric study based on the French MS database. Patients who initiated a HAT within 5 years after MS onset, EDSS ⩽4, and had a follow-up >5 years were included. The association of each covariate at baseline with time to the occurrence of SPMS was quantified by hazard ratios (HRs) in unadjusted and adjusted Cox proportional hazards models.

Results: Two thousand two hundred and thirty-seven patients were included in the analysis: mean age 31.6 years, female/male sex ratio 2.3, and median EDSS 2.0. The estimated probability of reaching SPMS, progression independent of relapse activity (PIRA) and progression independent of activity (PIA) at 10 years was 8%, 22%, and 11%, respectively. After adjustment, we found that female patients (HR 0.64, p = 0.036) had a lower risk of developing SPMS. Older age, EDSS >0 (HR 7.44, p < 0.001), and oral versus intravenous HAT (HR 1.97, p = 0.003) were significantly associated with an increased SPMS risk. Early PIRA and PIA predicted conversion to SPMS.

Conclusions: Early HAT use resulted in a low risk of developing SPMS over 10 years. Introducing the HAT before any residual disability was associated with a lower risk of progression.

Keywords: disability; multiple sclerosis.

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Conflict of interest statement

Mikael Cohen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Merck, Sanofi, Roche, Celgene‐BMS, Janssen, Alexion, Horizon Therapeutics, and Ad Scientiam. Fabien Rollot, Marc Debouverie, Helene Zephir, Jerome de Seze, Eric Berger, David Laplaud, Emmanuelle Le Page, Caroline Papeix, Eric Thouvenot, Abdullatif Al Khedr, Bruno Stankoff, Jean Pelletier, Olivier Casez, Thibault Moreau, Pierre Clavelou, Philippe Cabre, Solene Moulin, Jean Philippe Neau, Karolina Hankiewicz, Ines Doghri, Haifa Ben Nasr, Corinne Pottier, Laurent Magy, Dalia Dimitri, Olivier Heinzlef, Jean Philippe Camdessanche, Marc Coustans, Chantal Nifle, Romain Casey, David Brassat, and Christine Lebrun Frenay have nothing to disclose. Sandra Vukusic has received lecturing fees, travel grants, and research support from Biogen, BMS‐Celgene, Janssen, Merck, Novartis, Roche, Sandoz, and Sanofi‐Genzyme. Pierre Labauge received honoraria/grants from Biogen, Novartis, Sanofi Genzyme, Roche, Novartis, and Merck. Aurélie Ruet received honoraria for meeting speaking from Merck, Alexion, Horizon TH, and Sanofi Genzyme. A Ruet received support for traveling from Biogen, Novartis, and Merck. Her institution received research grants from Biogen, Roche, Sanofi‐Genzyme, and BMS.

Jonathan Ciron has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Novartis, Merck, Sanofi, Roche, BMS, Alexion, Horizon Therapeutics, none related to this study. Bertrand Bourre serves on the scientific advisory board and has received funding for travel and honoraria from Alexion, Biogen, BMS, Horizon, Janssen, Merck, Novartis, Sanofi, and Roche. Elisabeth Maillart reports research support from Biogen and personal fees for lectures and advisory boards from Alexion, Biogen, Horizon, Janssen, Merck, Novartis, Roche, Sanofi, and Teva. Gilles Defer received personal compensation for the scientific advisory board from Biogen, BMS, Novartis, Genzyme, Roche, and Teva Pharmaceutical Industries Ltd. funding for travel and/or speaker honoraria from Merck Serono, Biogen, BMS, Novartis, Roche, Genzyme, and Teva Pharmaceutical Industries Ltd. His institution received grants supporting research for my department from Merck Serono, Biogen, Genzyme, and Novartis. Mickael Zedet reported receiving personal fees from Novartis and Alexion, meeting invitations from Merck, Roche, Sanofi, and Sandoz, and travel expenses from Merk, Sandoz, and Novartis outside the submitted work.

Figures

FIGURE 1
FIGURE 1
Study flowchart.
FIGURE 2
FIGURE 2
Cumulative probabilities of reaching secondary progressive MS (SPMS), Progression Independent of Relapse Activity (PIRA), and Progression Independent of Activity (PIA) during follow‐up.
FIGURE 3
FIGURE 3
Probability of reaching secondary progressive MS depending on PIRA (a) and PIA (b) status.
See this image and copyright information in PMC

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