Giovanni Novi1, Francesca Bovis2, Marco Capobianco3, Jessica Frau4, Giorgia Mataluni5, Erica Curti6, Luigi Zuliani7, Paola Cavalla8, Laura Brambilla9, Pietro Annovazzi10, Anna Maria Repice11, Roberta Lanzillo12, Sabrina Esposito13, Luana Benedetti1, Ilaria Maietta2, Francesco Sica14, Fabio Buttari14, Simona Malucchi3, Giuseppe Fenu4, Doriana Landi5, Chiara Bosa15, Sabrina Realmuto3, Maria Malentacchi16, Franco Granella6, Alessio Signori2, Simona Bonavita13, Antonio Uccelli1, Maria Pia Sormani17. 1. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy; Ospedale Policlinico San Martino - IRCCS, Genoa, Italy. 2. Department of Health Sciences (DISSAL), Section of Biostatistics, University of Genova, Genova, Italy. 3. SCDO Neurologia e Centro di Riferimento Regionale Sclerosi Multipla, AOU San Luigi, Orbassano, Italy. 4. Department of Medical Sciences and Public Health, University of Cagliari, Italy. 5. Multiple sclerosis unit, Department of system medicine, University of Rome Tor Vergata, Italy. 6. Neurosciences Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy. 7. Neurology Unit, ULSS 2 Marca Trevigiana, Ca' Foncello Hospital, Treviso, Italy. 8. MS Center, Department of Neurosciences, City of Health & Science University Hospital of Turin, Turin, Italy. 9. Department of Neuroimmunology and Neuromuscular Diseases, Neurological Institute C. Besta, IRCCS Foundation, Milan, Italy. 10. MS Center, ASST-Valle Olona, PO di Gallarate, Gallarate, VA, Italy. 11. Regional MS Center, University Hospital "Careggi", Florence, Italy. 12. Federico II University, Naples, Italy. 13. Department of Neurology, University of Campania, Luigi Vanvitelli, Naples, Italy. 14. IRCCS Istituto Neurologico Mediterraneo- Neuromed, Pozzilli, IS, Italy. 15. University of Turin, Italy. 16. Experimental Biomedicine and Clinical Neuroscience Department (BioNeC), University of Palermo, Palermo, Italy. 17. Ospedale Policlinico San Martino - IRCCS, Genoa, Italy; Department of Health Sciences (DISSAL), Section of Biostatistics, University of Genova, Genova, Italy. Electronic address: mariapia.sormani@unige.it.
Abstract
OBJECTIVE: To evaluate disease activity according to rituximab (RTX) induction and maintenance regimens in a multicenter real-life dataset of NMOSD patients. METHODS: This is an observational-retrospective multicentre study including patients with NMOSD treated with RTX in 21 Italian and 1 Swiss centers. Demographics, relapse rate and adverse events over the follow-up were summarized taking into account induction strategy (two-1 g infusions at a 15-day interval (IND-A) vs. 375 mg/m2/week infusions for one month (IND-B)) and maintenance therapy (regimen A (M-A) with fixed time-points infusions vs. regimen B (M-B) based on cytofluorimetric driven reinfusion regimens, the least further subdivided according to CD19+ B cells (M-B1) or CD27+ memory B cells (M-B2) monitoring). RESULTS: 131 subjects were enrolled, 127 patients completed the induction regimen and 119 patients had at least one follow-up visit and were included in the outcome analysis. Median follow-up was 1.7 years (range 0.1-11.6). Annualized relapse rate (ARR) was 1.7 in the year before RTX start and decreased to 0.19 during the follow-up. Both ARR and Time to first relapse (TTFR) analysis showed a trend toward an increased disease activity for IND-B and M-A. No patients with MT-B2 experienced relapses during the follow-up. Number of relapses in the year before RTX initiation and having received a previous treatment were significantly associated with higher ARR and reduced TTFR in the multivariate analysis. INTERPRETATION: We confirm RTX efficacy in NMOSD patients. Use of specific induction and maintenance protocols is warranted in order to foster RTX efficacy and to reduce costs and side effects.
OBJECTIVE: To evaluate disease activity according to rituximab (RTX) induction and maintenance regimens in a multicenter real-life dataset of NMOSD patients. METHODS: This is an observational-retrospective multicentre study including patients with NMOSD treated with RTX in 21 Italian and 1 Swiss centers. Demographics, relapse rate and adverse events over the follow-up were summarized taking into account induction strategy (two-1 g infusions at a 15-day interval (IND-A) vs. 375 mg/m2/week infusions for one month (IND-B)) and maintenance therapy (regimen A (M-A) with fixed time-points infusions vs. regimen B (M-B) based on cytofluorimetric driven reinfusion regimens, the least further subdivided according to CD19+ B cells (M-B1) or CD27+ memory B cells (M-B2) monitoring). RESULTS: 131 subjects were enrolled, 127 patients completed the induction regimen and 119 patients had at least one follow-up visit and were included in the outcome analysis. Median follow-up was 1.7 years (range 0.1-11.6). Annualized relapse rate (ARR) was 1.7 in the year before RTX start and decreased to 0.19 during the follow-up. Both ARR and Time to first relapse (TTFR) analysis showed a trend toward an increased disease activity for IND-B and M-A. No patients with MT-B2 experienced relapses during the follow-up. Number of relapses in the year before RTX initiation and having received a previous treatment were significantly associated with higher ARR and reduced TTFR in the multivariate analysis. INTERPRETATION: We confirm RTX efficacy in NMOSD patients. Use of specific induction and maintenance protocols is warranted in order to foster RTX efficacy and to reduce costs and side effects.
Authors: Jonas Graf; Jan Mares; Michael Barnett; Orhan Aktas; Philipp Albrecht; Scott S Zamvil; Hans-Peter Hartung Journal: Neurol Neuroimmunol Neuroinflamm Date: 2020-12-16