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Active and non-active progression independent of relapse activity within the first 20 years of relapsing multiple sclerosis
  1. Adil Maarouf1,2,
  2. Jan Patrick Stellmann2,3,
  3. Audrey Rico1,2,
  4. Clemence Boutiere1,
  5. Sarah Demortiere1,
  6. Pierre Durozard4,
  7. Wafaa Zaaraoui2,
  8. Jean-Philippe Ranjeva2,
  9. Jean Pelletier1,2,
  10. Bertrand Audoin1,2
  1. 1Pôle de Neurosciences Cliniques, Service de Neurologie, Assistance Publique Hopitaux de Marseille, Marseille, France
  2. 2Aix-Marseille Univ, CRMBM, CNRS UMR 7339, Marseille, France
  3. 3Département de Neuroradiologie, Assistance Publique Hopitaux de Marseille, Marseille, France
  4. 4Centre Hospitalier d'Ajaccio, Ajaccio, France
  1. Correspondence to Dr Bertrand Audoin, Assistance Publique Hopitaux de Marseille, Marseille, France; bertrand.audoin{at}


Background Progression independent of relapse activity (PIRA) has been described since the early stage of relapsing multiple sclerosis (RMS). However, little is known about the relation between PIRA and inflammatory activity that is particularly important at this stage of the disease.

Method We included 110 patients in a prospective study within 18 months of RMS onset. MRI examinations and clinical visits were scheduled on the same day for months 0, 6, 12, 24, 36, 60, 84, 120, 180 and 240.

Results The mean (SD) age of patients was 30 (6.7) years at inclusion and median (range) follow-up 15 (9–20) years. Analysis of 1118 between-visit intervals revealed 93 confirmed disability accumulation events in 68 (62%) patients: 50 (54%) events related to relapse activity worsening and 43 (46%) PIRA events, including 17 (18%) with MRI activity. The risk of PIRA between two visits (stable event as the reference category) was associated with Expanded Disability Status Scale (EDSS) score (HR: 1.41; 95% CI: 1.18 to 1.69; p<0.001), disease duration (HR: 0.75; 95% CI: 0.62 to 0.90; p<0.005) and new lesions between the visits (HR: 1.09 per lesion; 95% CI: 1.01 to 1.17; p<0.05). As compared with PIRA events with MRI activity, PIRA events without such activity occurred in patients with more disability (mean EDSS score 3, p<0.05), longer disease duration (mean 11 years, p<0.001) and greater number of T2-weighted lesions (p<0.05).

Conclusion This study evidenced that inflammatory activity increases the risk of PIRA in early RMS, arguing that a significant part of PIRA is accessible to treatment targeting inflammation in these patients.


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  • Contributors AM played a major role in the acquisition of the data and the gathering of data. JPS played a major role in the acquisition of the data and conducted statistical analysis. AR, CB, SD and WZ played a major role in the acquisition of the data. J-PR and JP planned the study and played a major role in the acquisition of the data. BA planned and conducted the study, conducted statistical analysis and wrote the manuscript.

  • Funding This study was supported by Fondation pour l’Aide à la Recherche sur la Sclérose En Plaques (ARSEP Fondation)

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.