PMID- 33844155
OWN - NLM
STAT- MEDLINE
DCOM- 20220202
LR  - 20240204
IS  - 1878-7479 (Electronic)
IS  - 1933-7213 (Print)
IS  - 1878-7479 (Linking)
VI  - 18
IP  - 2
DP  - 2021 Apr
TI  - Exit Strategies in Natalizumab-Treated RRMS at High Risk of Progressive 
      Multifocal Leukoencephalopathy: a Multicentre Comparison Study.
PG  - 1166-1174
LID - 10.1007/s13311-021-01037-2 [doi]
AB  - The main aim of the study is to evaluate the efficacy and safety profile of 
      ocrelizumab (OCR), rituximab (RTX), and cladribine (CLA), employed as natalizumab 
      (NTZ) exit strategies in relapsing-remitting multiple sclerosis (RRMS) patients 
      at high-risk for progressive multifocal leukoencephalopathy (PML). This is a 
      multicentre, retrospective, real-world study on consecutive RRMS patients from 
      eleven tertiary Italian MS centres, who switched from NTZ to OCR, RTX, and CLA 
      from January 1st, 2019, to December 31st, 2019. The primary study outcomes were 
      the annualized relapse rate (ARR) and magnetic resonance imaging (MRI) outcome. 
      Treatment effects were estimated by the inverse probability treatment weighting 
      (IPTW), based on propensity-score (PS) approach. Additional endpoint included 
      confirmed disability progression (CDP) as measured by Expanded Disability Status 
      Scale and adverse events (AEs). Patients satisfying predefined inclusion and 
      exclusion criteria were 120; 64 switched to OCR, 36 to RTX, and 20 to CLA. 
      Patients from the 3 groups did not show differences for baseline characteristics, 
      also after post hoc analysis. The IPTW PS-adjusted models revealed that patients 
      on OCR had a lower risk for ARR than patients on CLA (ExpB(OCR) 0.485, CI 95% 
      0.264-0.893, p = 0.020). This result was confirmed also for 12-month MRI activity 
      (ExpB(OCR) 0.248 CI 95% 0.065-0.948, p = 0.042). No differences were found in 
      other pairwise comparisons (OCR vs RTX and RTX vs CLA) for the investigated 
      outcomes. AEs were similar among the 3 groups. Anti-CD20 drugs were revealed to 
      be effective and safe options as NTZ exit strategies. All investigated DMTs 
      showed a good safety profile.
CI  - (c) 2021. The Author(s).
FAU - Zanghi, Aurora
AU  - Zanghi A
AUID- ORCID: 0000-0002-9566-3135
AD  - Department "G.F. Ingrassia", MS Center, Organization University of Catania, 
      Catania, Italy.
FAU - Gallo, Antonio
AU  - Gallo A
AD  - MS Center I Division of Neurology, University Della Campania "L. Vanvitelli", 
      Naples, Italy.
FAU - Avolio, Carlo
AU  - Avolio C
AD  - Department of Medical and Surgical Sciences Head of Multiple Sclerosis Center 
      Dept. of Neurosciences, University of Foggia, Foggia, Italy.
FAU - Capuano, Rocco
AU  - Capuano R
AD  - MS Center I Division of Neurology, University Della Campania "L. Vanvitelli", 
      Naples, Italy.
FAU - Lucchini, Matteo
AU  - Lucchini M
AD  - Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Istituto di Neurologia, 
      Universita Cattolica del Sacro Cuore, Rome, Italy.
FAU - Petracca, Maria
AU  - Petracca M
AD  - Department of Neuroscience, Reproductive Sciences and Odontostomatology, 
      University of Naples "Federico II", Naples, Italy.
FAU - Bonavita, Simona
AU  - Bonavita S
AD  - Dipartimento Di Scienze Mediche E Chirurgiche Avanzate, Universita Della Campania 
      Luigi Vanvitelli, Piazza Miraglia, 2, 80138, Naples, Italy.
FAU - Lanzillo, Roberta
AU  - Lanzillo R
AD  - Department of Neuroscience, Reproductive Sciences and Odontostomatology, 
      University of Naples "Federico II", Naples, Italy.
FAU - Ferraro, Diana
AU  - Ferraro D
AD  - University of Modena and Reggio Emilia, Modena, Italy.
FAU - Curti, Erica
AU  - Curti E
AD  - Multiple Sclerosis Centre, Department of General Medicine, Parma University 
      Hospital, Parma, Italy.
FAU - Buccafusca, Maria
AU  - Buccafusca M
AD  - Azienda Ospedaliera Universitaria "G. Martino", Messina, Italy.
FAU - Callari, Graziella
AU  - Callari G
AD  - Institute Foundation "G. Giglio", Cefalu, Italy.
FAU - Barone, Stefania
AU  - Barone S
AD  - Azienda Ospedaliera Universitaria "Mater Domini", Catanzaro, Italy.
FAU - Pontillo, Giuseppe
AU  - Pontillo G
AD  - Department of Advanced Biomedical Sciences, University "Federico II", Naples, 
      Italy.
AD  - Department of Electrical Engineering and Information Technology, , University 
      "Federico II", Naples, Italy.
FAU - Abbadessa, Gianmarco
AU  - Abbadessa G
AD  - Dipartimento Di Scienze Mediche E Chirurgiche Avanzate, Universita Della Campania 
      Luigi Vanvitelli, Piazza Miraglia, 2, 80138, Napoli, Italy.
FAU - Di Francescantonio, Valeria
AU  - Di Francescantonio V
AD  - Department of Medical and Surgical Sciences Head of Multiple Sclerosis Center 
      Dept. of Neurosciences, University of Foggia, Foggia, Italy.
FAU - Signoriello, Elisabetta
AU  - Signoriello E
AD  - Department of Clinical and Experimental Medicine, Multiple Sclerosis Center, II 
      Division of Neurology, Second University of Naples, Naples, Italy.
FAU - Lus, Giacomo
AU  - Lus G
AD  - Department of Clinical and Experimental Medicine, Multiple Sclerosis Center, II 
      Division of Neurology, Second University of Naples, Naples, Italy.
FAU - Sola, Patrizia
AU  - Sola P
AD  - University of Modena and Reggio Emilia, Modena, Italy.
FAU - Granella, Franco
AU  - Granella F
AD  - Multiple Sclerosis Centre, Department of General Medicine, Parma University 
      Hospital, Parma, Italy.
AD  - Unit of Neurosciences, Department of Medicine and Surgery, University of Parma, 
      Parma, Italy.
FAU - Valentino, Paola
AU  - Valentino P
AD  - Azienda Ospedaliera Universitaria "Mater Domini", Catanzaro, Italy.
FAU - Mirabella, Massimiliano
AU  - Mirabella M
AD  - Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Istituto di Neurologia, 
      Universita Cattolica del Sacro Cuore, Rome, Italy.
AD  - Universita Cattolica del Sacro Cuore, Rome, Italy.
FAU - Patti, Francesco
AU  - Patti F
AD  - Department "G.F. Ingrassia", MS Center, Organization University of Catania, 
      Catania, Italy.
FAU - D'Amico, Emanuele
AU  - D'Amico E
AUID- ORCID: 0000-0001-7494-9057
AD  - Department "G.F. Ingrassia", MS Center, Organization University of Catania, 
      Catania, Italy. emanuele.damico@unict.it.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Observational Study
PT  - Pragmatic Clinical Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20210412
PL  - United States
TA  - Neurotherapeutics
JT  - Neurotherapeutics : the journal of the American Society for Experimental 
      NeuroTherapeutics
JID - 101290381
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Immunologic Factors)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Natalizumab)
RN  - 47M74X9YT5 (Cladribine)
RN  - 4F4X42SYQ6 (Rituximab)
RN  - A10SJL62JY (ocrelizumab)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antibodies, Monoclonal, Humanized/administration & dosage
MH  - Cladribine/administration & dosage
MH  - Drug Substitution/*methods/trends
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Immunologic Factors/administration & dosage/*adverse effects
MH  - Immunosuppressive Agents/*administration & dosage
MH  - Leukoencephalopathy, Progressive Multifocal/*chemically induced/diagnostic 
      imaging/epidemiology
MH  - Male
MH  - Multiple Sclerosis, Relapsing-Remitting/diagnostic imaging/*drug 
      therapy/epidemiology
MH  - Natalizumab/administration & dosage/*adverse effects
MH  - Prospective Studies
MH  - Retrospective Studies
MH  - Risk Factors
MH  - Rituximab/administration & dosage
MH  - Young Adult
PMC - PMC8423885
OTO - NOTNLM
OT  - Cladribine
OT  - Disease activity
OT  - Exit strategy
OT  - Natalizumab
OT  - Ocrelizumab
OT  - Rituximab
EDAT- 2021/04/13 06:00
MHDA- 2022/02/03 06:00
PMCR- 2021/04/12
CRDT- 2021/04/12 12:48
PHST- 2021/03/09 00:00 [accepted]
PHST- 2021/04/13 06:00 [pubmed]
PHST- 2022/02/03 06:00 [medline]
PHST- 2021/04/12 12:48 [entrez]
PHST- 2021/04/12 00:00 [pmc-release]
AID - S1878-7479(23)01155-8 [pii]
AID - 1037 [pii]
AID - 10.1007/s13311-021-01037-2 [doi]
PST - ppublish
SO  - Neurotherapeutics. 2021 Apr;18(2):1166-1174. doi: 10.1007/s13311-021-01037-2. 
      Epub 2021 Apr 12.