{
  "abstract": "Background Three decades have passed since the initial approval of disease-modifying therapies (DMTs). Ongoing discussion is focused on fundamental aspects of the disease, highlighting a growing division between successes in managing relapsing multiple sclerosis (MS) and the persistent challenges posed by disease progression.Methods A cohort study on prospectively acquired data from the Italian MS register. The primary outcome was to describe the MS disease course from onset to secondary progression (SP) defined according to a data-driven algorithm over 30 years follow-up and according to five different eras of disease onset.Results A total cohort of 9958 patients was analysed; 1364 converted to SP after a mean of 8.5 (SD 5.5) years. A higher rate of patients converting to SP had never been exposed to DMTs (135, 9.9% vs 424, 5.2%) than non-converting ones. The treatment coverage was also lower in patients converting to SP than non-converting ones 58.4 (SD 31.5) vs 73.6 (SD 27.6).The SP incidence rate was 1.26 (95% CI 1.19 to 1.32) overall. The rates showed a downward trend among the different eras: from 1st era 1.98 (95% CI 1.73 to 2.27) to 5th era 1.15 (95% CI 0.97 to 1.35).In the multivariable Cox model, 10% increase of treatment coverage was associated to 19% lower risk to convert to SP (10%, HR 0.89, 95% CI 0.87 to 0.90).Conclusions This 30-year analysis suggests that SP conversion rates have decreased over time, partially explained by improvements in therapeutic coverage. Future research should adopt a multifaceted approach to develop more comprehensive models of disease progression.",
  "authors": [
    {
      "affiliations": [
        "Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy"
      ],
      "name": "Aurora Zanghì"
    },
    {
      "affiliations": [
        "Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy"
      ],
      "name": "Massimiliano Copetti"
    },
    {
      "affiliations": [
        "Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy"
      ],
      "name": "Carlo Avolio"
    },
    {
      "affiliations": [
        "Department of Translational Biomedicines and Neurosciences, University of Bari Aldo Moro, Bari, Italy"
      ],
      "name": "Damiano Paolicelli"
    },
    {
      "affiliations": [
        "Neurology, San Raffaele Hospital, Milan, Italy"
      ],
      "name": "Marzia Anita Lucia Romeo"
    },
    {
      "affiliations": [
        "University of Catania, Catania, Italy"
      ],
      "name": "Francesco Patti"
    },
    {
      "affiliations": [
        "Centro Sclerosi Multipla, Clinica Neurologica, Ospedale SS Annunziata, Università degli Studi Gabriele d’Annunzio Chieti Pescara, Chieti, Italy"
      ],
      "name": "Giovanna De Luca"
    },
    {
      "affiliations": [
        "Department of Neurological Siences, University of Florence, Florence, Italy"
      ],
      "name": "Maria Pia Amato"
    },
    {
      "affiliations": [
        "San Camillo Forlanini Hospital, Roma, Italy"
      ],
      "name": "Simonetta Galgani"
    },
    {
      "affiliations": [
        "Department of Neuroscience, S. Agostino-Estense Hospital and University of Modena and Reggio Emilia, Modena, Italy"
      ],
      "name": "Patrizia Sola"
    },
    {
      "affiliations": [
        "Department of Experimental Medicine and Clinical Neurosciences, University of Palermo, Palermo, Italy"
      ],
      "name": "Giuseppe Salemi"
    },
    {
      "affiliations": [
        "Department of Neurosciences, University Hospital, Multiple Sclerosis Centre of Veneto Region, First Neurology Clinic, Padova, Italy"
      ],
      "name": "Paolo Gallo"
    },
    {
      "affiliations": [
        "Neurosciences, Multiple Sclerosis Center, University of Parma, Parma, Italy"
      ],
      "name": "Franco Granella"
    },
    {
      "affiliations": [
        "Center for Experimental Neurological Therapy, S. Andrea Hospital, University of Rome, La Sapienza, Rome, Italy"
      ],
      "name": "Silvia Romano"
    },
    {
      "affiliations": [
        "Multiple Sclerosis Centre, Azienda Ospedaliera Sant\\’Antonio Abate di Gallarate, Gallarate, Italy"
      ],
      "name": "Mauro Zaffaroni"
    },
    {
      "affiliations": [
        "Multiple Sclerosis Centre, Neurological Institute C.Mondino, Pavia, Italy"
      ],
      "name": "Roberto Bergamaschi"
    },
    {
      "affiliations": [
        "Sapienza University, Roma, Italy"
      ],
      "name": "Carlo Pozzilli"
    },
    {
      "affiliations": [
        "Università della Campania Luigi Van Vitelli, Naples, Italy"
      ],
      "name": "Giacomo Lus"
    },
    {
      "affiliations": [
        "OU Neurology, Unit of Neurology, Treviso, Italy"
      ],
      "name": "Marika Vianello"
    },
    {
      "affiliations": [
        "Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Bari, Italy"
      ],
      "name": "Maria Trojano"
    },
    {
      "affiliations": [
        "Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy"
      ],
      "name": "Emanuele D’Amico"
    },
    {
      "affiliations": [],
      "name": "for the Italian Multiple Sclerosis register"
    }
  ],
  "title": "Multiple sclerosis from onset to secondary progression: a 30-year Italian register study",
  "uid": "3f5444aa-dc08-5513-9735-65e9543730b6"
}