Risk of Persistent Disability in Patients With Pediatric-Onset Multiple Sclerosis
Authors: Damiano Baroncini, Marta Simone, Pietro Iaffaldano, Vincenzo Brescia Morra, Roberta Lanzillo, Massimo Filippi, Marzia Romeo, Francesco Patti, Clara Grazia Chisari, Eleonora Cocco, Giuseppe Fenu, Giuseppe Salemi, Paolo Ragonese, Matilde Inglese, Maria Cellerino, Lucia Margari, Giancarlo Comi, Mauro Zaffaroni, Angelo Ghezzi, Umberto Aguglia, Maria P. Amato, Roberto Balgera, Paola Banfi, Valeria Barcella, Paolo Bellantonio, Roberto Bergamaschi, Antonio Bertolotto, Roberto Bombardi, Ardito Bonaventura, Placido Bramati, Giampaolo Brichetto, Lorenzo Capone, Daniela Cargnelutti, Elisabetta Cartechini, Guido Cavaletti, Paola Cavalla, Luca Chiveri, Raffaella Clerici, Marinella Clerico, Cristoforo Comi, Francesco Corea, Salvatore Cottone, Paola Crociani, Francesco D'Andrea, Maura C. Danni, Francesca De Robertis, Mario Di Napoli, Alessia Di Sapio, Diana Ferraro, Elisabetta Ferraro, Maria T. Ferrò, Antonio Gallo, Claudio Gasperini, Maurizia Gatto, Paola Gazzola, Franco Granella, Maria G. Grasso, Alessandra Lugaresi, Giacomo Lus, Davide Maimone, Giorgia T. Maniscalco, Girolama Marfia, Nerina Mascoli, Luca Massacesi, Massimiliano Mirabella, Fiorella Mondino, Sara Montepietra, Davide Nauselli, Marco Onofrj, Sergio Parodi, Ilaria Pesci, Carlo Piantadosi, Carlo Pozzilli, Alessandra Protti, Rocco Quatrale, Augusto Rini, Marco Rovaris, Marco Salvetti, Giuseppe Santuccio, Elio Scarpini, Leonardo Sinisi, Patrizia Sola, Daniele Spitaleri, Silvia Strumia, Tiziana Tassinari, Simone Tonietti, Valentina Torri Clerici, Rocco Totaro, Paola Valentino, Simonetta Venturi, Marika Vianello
Journal: JAMA Neurology (2021)

Availability of new disease-modifying therapies (DMTs) and changes of therapeutic paradigms have led to a general improvement of multiple sclerosis (MS) prognosis in adults. It is still unclear whether this improvement also involves patients with pediatric-onset MS (POMS), whose early management is more challenging.To evaluate changes in the prognosis of POMS over time in association with changes in therapeutic and managing standards.Retrospective, multicenter, observational study. Data were extracted and collected in May 2019 from the Italian MS Registry, a digital database including more than 59 000 patients. Inclusion criteria were MS onset before age 18 years, diagnosis before January 2014, and disease duration of at least 3 years. Exclusion criteria were primary progressive MS, Expanded Disability Status Scale (EDSS) score of at least 8 one year after onset, unavailability of diagnosis date, and less than 2 EDSS score evaluations. Eligible patients were 4704 patients with POMS. According to these criteria, we enrolled 3198 patients, excluding 1506.We compared time to reach disability milestones by epoch of MS diagnosis (<1993, 1993-1999, 2000-2006, and 2007-2013), adjusting for possible confounders linked to EDSS evaluations and clinical disease activity. We then analyzed the difference among the 4 diagnosis epochs regarding demographic characteristics, clinical disease activity at onset, and DMTs management.Disability milestones were EDSS score 4.0 and 6.0, confirmed in the following clinical evaluation and in the last available visit.We enrolled 3198 patients with POMS (mean age at onset, 15.2 years; 69% female; median time to diagnosis, 3.2 years; annualized relapse rate in first 1 and 3 years, 1.3 and 0.6, respectively), with a mean (SD) follow-up of 21.8 (11.7) years. Median survival times to reach EDSS score of 4.0 and 6.0 were 31.7 and 40.5 years. The cumulative risk of reaching disability milestones gradually decreased over time, both for EDSS score of 4.0 (hazard ratio [HR], 0.70; 95% CI, 0.58-0.83 in 1993-1999; HR, 0.48; 95% CI, 0.38-0.60 in 2000-2006; and HR, 0.44; 95% CI, 0.32-0.59 in 2007-2013) and 6.0 (HR, 0.72; 95% CI, 0.57-0.90; HR, 0.44; 95% CI, 0.33-0.60; and HR, 0.30; 0.20-0.46). In later diagnosis epochs, a greater number of patients with POMS were treated with DMTs, especially high-potency drugs, that were given earlier and for a longer period. Demographic characteristics and clinical disease activity at onset did not change significantly over time.In POMS, the risk of persistent disability has been reduced by 50% to 70% in recent diagnosis epochs, probably owing to improvement in therapeutic and managing standards.