Hematopoietic Stem Cell Transplantation in People With Active Secondary Progressive Multiple Sclerosis
Giacomo Boffa, Alessio Signori, Luca Massacesi, Alice Mariottini, Elvira Sbragia, Salvatore Cottone, Maria Pia Amato, Claudio Gasperini, Lucia Moiola, Stefano Meletti, Anna Maria Repice, Vincenzo Brescia Morra, Giuseppe Salemi, Francesco Patti, Massimo Filippi, Giovanna De Luca, Giacomo Lus, Mauro Zaffaroni, Patrizia Sola, Antonella Conte, Riccardo Nistri, Umberto Aguglia, Franco Granella, Simonetta Galgani, Luisa Caniatti, Alessandra Lugaresi, Silvia Romano, Pietro Iaffaldano, Eleonora Cocco, Riccardo Saccardi, Emanuele Angelucci, María Trojano, Giovanni Luigi Mancardi, Maria Pia Sormani, Matilde Inglese, on behalf of the Italian BMT-MS Study Group and the Italian MS Register, Marco Capobianco, Giovanni Bosco Zimatore, Jessica Frau, Elio Scarpini, Giuseppe Meucci, Donata Guidetti, Francesca Gualandi, Riccardo Varaldo, Anna Maria Raiola, Chiara Innocenti, Valerio Zoli, Fabio Ciceri, Raffaella Greco, Rosanna Scim`e, Marco De Gobbi, Alessandro Barilaro
Abstract
Background and ObjectivesUncontrolled evidence suggests that autologous hematopoietic stem cell transplantation (AHSCT) can be effective in people with active secondary progressive multiple sclerosis (SPMS). In this study, we compared the effect of AHSCT with that of other anti-inflammatory disease-modifying therapies (DMTs) on long-term disability worsening in active SPMS. MethodsWe collected data from the Italian Bone Marrow Transplantation Study Group and the Italian Multiple Sclerosis Register. Patients were considered eligible if treatment had been started after the diagnosis of SPMS. Disability worsening was assessed by the cumulative proportion of patients with a 6-month confirmed disability progression (CDP) according to the Expanded Disability Status Scale (EDSS) score. Key secondary endpoints were the EDSS time trend after treatment start and the prevalence of disability improvement over time. Time to first CDP was assessed by means of proportional hazard Cox regression models. A linear mixed model with a time × treatment group interaction was used to assess the longitudinal EDSS time trends. Prevalence of improvement was estimated using a modified Kaplan-Meier estimator and compared between groups by bootstrapping the area under the curve. ResultsSeventy-nine AHSCT-treated patients and 1975 patients treated with other DMTs (beta interferons, azathioprine, glatiramer-acetate, mitoxantrone, fingolimod, natalizumab, methotrexate, teriflunomide, cyclophosphamide, dimethyl fumarate, and alemtuzumab) were matched to reduce treatment selection bias using propensity score and overlap weighting approaches. Time to first CDP was significantly longer in transplanted patients (hazard ratio [HR] = 0.50; 95% CI = 0.31–0.81; p = 0.005), with 61.7% of transplanted patients free from CPD at 5 years. Accordingly, EDSS time trend over 10 years was higher in patients treated with other DMTs than in AHSCT-treated patients (+0.157 EDSS points per year compared with −0.013 EDSS points per year; interaction p < 0.001). Patients who underwent AHSCT were more likely to experience a sustained disability improvement: 34.7% of patients maintained an improvement (a lower EDSS than baseline) 3 years after transplant vs 4.6% of patients treated by other DMTs (p < 0.001). DiscussionThe use of AHSCT in people with active SPMS is associated with a slowing of disability progression and a higher likelihood of disability improvement compared with standard immunotherapy. Classification of EvidenceThis study provides Class III evidence that autologous hematopoietic stem cell transplants prolonged the time to CDP compared with other DMTs.