Towards a validated definition of the clinical transition to secondary progressive multiple sclerosis: A study from the Italian MS Register

Pietro Iaffaldano, Giuseppe Lucisano, Tommaso Guerra, Francesco Patti, Marco Onofrj, Vincenzo Brescia Morra, Mauro Zaffaroni, Carlo Pozzilli, Eleonora Cocco, Patrizia Sola, Giuseppe Salemi, Matilde Inglese, Roberto Bergamaschi, Claudio Gasperini, Antonella Conte, Marco Salvetti, Giacomo Lus, Giorgia Teresa Maniscalco, Rocco Totaro, Marika VianelloFranco Granella, Elisabetta Ferraro, Umberto Aguglia, Maurizia Gatto, Francesca Sangalli, Clara Grazia Chisari, Giovanna De Luca, Antonio Carotenuto, Damiano Baroncini, Delia Colombo, Mihaela Nica, Damiano Paolicelli, Giancarlo Comi, Massimo Filippi, Maria Pia Amato, Maria Trojano

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Background: Definitions for reliable identification of transition from relapsing-remitting multiple sclerosis (MS) to secondary progressive (SP)MS in clinical cohorts are not available. Objectives: To compare diagnostic performances of two different data-driven SPMS definitions. Methods: Data-driven SPMS definitions based on a version of Lorscheider’s algorithm (DDA) and on the EXPAND trial inclusion criteria were compared, using the neurologist’s definition (ND) as gold standard, in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), Akaike information criterion (AIC) and area under the curve (AUC). Results: A cohort of 10,240 MS patients with ⩾5 years of follow-up was extracted from the Italian MS Registry; 880 (8.5%) patients were classified as SPMS according to the neurologist definition, 1806 (17.6%) applying the DDA and 1134 (11.0%) with the EXPAND definition. The DDA showed greater discrimination power (AUC: 0.8 vs 0.6) and a higher sensitivity (77.1% vs 38.0%) than the EXPAND definition, with similar specificity (88.0% vs 91.5%). PPV and NPV were higher using the DDA than considering EXPAND definition (37.5% vs 29.5%; 97.6% vs 94.0%). Conclusion: Data-driven definitions demonstrated greater ability to capture SP transition than neurologist’s definition and the global accuracy of DDA seems to be higher than the EXPAND definition.

Original languageEnglish
Pages (from-to)2243-2252
Number of pages10
JournalMultiple Sclerosis Journal
Issue number14
StatePublished - Dec 2022
Externally publishedYes


  • Multiple sclerosis
  • big data
  • data-driven algorithm
  • disease registry
  • prognosis
  • secondary progressive


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