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ND was defined according to clinical criteria for SPMS and the HERCULES cohort adapting the trial inclusion criteria. Progression independent from relapse activity (PIRA) and relapse-associated worsening (RAW) events were assessed. Diagnostic performances of SPMS definitions were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 20,306 patients, 866 (4.26%) were classified as SPMS by ND and 1603 (7.89%) by HERCULES criteria. The HERCULES group included older patients, less likely to relapse post-conversion. PIRA occurred in 88.8% of ND and 88.5% of HERCULES-defined cases, with a shorter median time to first PIRA in the latter. The HERCULES definition showed high specificity (93.4%) and low sensitivity (37.6%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HERCULES-adapted criteria identified a subgroup of 7.9% nrSPMS patients in the real-world cohort of RISM, characterized by fewer post-conversion relapses and earlier PIRA onset. 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They note, however, that patients included in the analysis received various disease-modifying therapies, and several authors have received honoraria, travel grants, consulting fees, research support, or participated in advisory boards sponsored by pharmaceutical companies, including Actelion, Allergan, Almirall, Alexion, Amgen, Bayer Schering, Biogen, Bristol Myers Squibb, Celgene, Excemed, Genzyme, Forward Pharma, Ipsen, Medday, Merck, Mylan, Novartis, Sanofi, Roche, Teva, and their affiliates.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"RISM was approved by the ethical committee at the \u201cAzienda Ospedaliero\u2014Universitaria\u2014Policlinico of Bari\u201d (Study REGISTRO SM001\u2014approved on 8 July 2016) and by local ethics committees in all participating centers.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Patients signed an informed consent to collect and use their clinical data for research purposes.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate and publication"}}],"article-number":"193"}}