COVID-19 outbreak in Italy: an opportunity to evaluate extended interval dosing of ocrelizumab in MS patients
Authors: Bisecco Alvino , Matrone Federica , Capobianco Marco , De Luca Giovanna , Filippi Massimo , Granella Franco , Lus Giacomo , Marfia Girolama Alessandra , Mirabella Massimiliano , Patti Francesco , Trojano Maria , Mascolo Agnese , Copetti Massimiliano , Tedeschi Gioacchino , Gallo Antonio ,   the OCREVID study group on behalf of the Italian MS Register, Malucchi Simona , Talentacci Maria , Tomassini Valentina , Farina Deborah , Moiola Lucia , Nozzolillo Agostino , Franceschini Alessandro , Minetti Matteo , Signoriello Elisabetta , Romano Giuseppe , Risi Mario , d’Ambrosio Alessandro , Landi Doriana , Nicoletti Carolina Gabri , Bianco Assunta , Lucchini Matteo , Chisari Clara , Toscano Simona , Paolicelli Damiano , Iaffaldano Pietro , Inglese Matilde , Cellerino Maria , Bellantonio Paolo , Fantozzi Roberta , Salemi Giuseppe , Ragonese Paolo , Danni Maura , Coniglio Gabriella , Ferraro Diana , Maniscalco Giorgia Teresa , Conte Antonella , Cavalla Paola , Vianello Marika , Cargnelutti Daniela , Gatto Maurizia , Buonaventura Ardito , Lugaresi Alessandra , Amato Maria Pia , Gazzola Paola , Iodice Rosa , Pesci Ilaria , Montepietra Sara , Pozzilli Carlo , Ferraro Elisabetta , Zaffaroni Mauro , Nasuelli Davide 
Published: November 2023

Abstract
Introduction
During the COVID-19 pandemic, ocrelizumab (OCR) infusions for MS patients were often re-scheduled because of MS center's disruption and concerns regarding immunosuppression. The aim of the present study was to assess changes in OCR schedule during the first wave of pandemic in Italy and to evaluate the effect of delayed infusion on clinical/radiological endpoints.

Methods
Data were extracted from the Italian MS Register database. Standard interval dosing was defined as an infusion interval ≤ 30 weeks, while extended interval dosing was defined as an infusion interval > 30 weeks at the time of the observation period. Clinico-demographics variables were tested as potential predictors for treatment delay. Time to first relapse and time to first MRI event were evaluated. Cumulative hazard curves were reported along their 95% confidence intervals. A final sample of one-thousand two patients with MS from 65 centers was included in the analysis: 599 pwMS were selected to evaluate the modification of OCR infusion intervals, while 717 pwRMS were selected to analyze the effect of infusion delay on clinical/MRI activity.

Results
Mean interval between two OCR infusions was 28.1 weeks before pandemic compared to 30.8 weeks during the observation period, with a mean delay of 2.74 weeks (p < 0.001). No clinico-demographic factors emerged as predictors of infusion postponement, except for location of MS centers in the North of Italy. Clinical relapses (4 in SID, 0 in EID) and 17 MRI activity reports (4 in SID, 13 in EID) were recorded during follow-up period.

Discussion
Despite the significant extension of OCR infusion interval during the first wave of pandemic in Italy, a very small incidence of clinical/radiological events was observed, thus suggesting durable efficacy of OCR, as well as the absence of rebound after its short-term suspension.