Extending the Interval of Natalizumab Dosing: Is Efficacy Preserved?

Marinella Clerico¹, Stefania Federica De Mercanti², Alessio Signori³, Marco Iudicello¹, Cinzia Cordioli⁴, Elisabetta Signoriello⁵, Giacomo Lus⁵, Simona Bonavita⁶, Luigi Lavorgna⁶, Giorgia Teresa Maniscalco⁷, Erica Curti⁸, Lorena Lorefice⁹, Eleonora Cocco⁹, Viviana Nociti¹⁰, Massimiliano Mirabella¹⁰, Damiano Baroncini¹¹, Giorgia Mataluni¹², Doriana Landi¹², Martina Petruzzo¹³, Roberta Lanzillo¹³, Ilaria Gandoglia¹⁴, Alice Laroni¹⁵, Rita Frangiamore¹⁶, Arianna Sartori¹⁷, Paola Cavalla¹⁸, Gianfranco Costantini¹⁸, Maria Pia Sormani³, Ruggero Capra⁴

Affiliations

¹ Clinical and Biological Sciences Department, Neurology Unit, University of Torino, San Luigi Gonzaga Hospital, Regione Gonzole, 10, Orbassano, 10043, Turin, Italy.
² Clinical and Biological Sciences Department, Neurology Unit, University of Torino, San Luigi Gonzaga Hospital, Regione Gonzole, 10, Orbassano, 10043, Turin, Italy. sdemercanti@yahoo.it.
³ Department of Health Sciences, Section of Biostatistics, University of Genova, Genoa, Italy.
⁴ Multiple Sclerosis Center, Spedali Civili of Brescia, Presidio di Montichiari, Brescia, Italy.
⁵ Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy.
⁶ Clinic of Neurology, AOU - University of Campania "Luigi Vanvitelli", Naples, Italy.
⁷ Neurological Clinic and Multiple Sclerosis Centre of "AORN A. Cardarelli", Naples, Italy.
⁸ Neurology Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy.
⁹ Multiple Sclerosis Center, Binaghi Hospital, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
¹⁰ Multiple Sclerosis Center, Neuroscience Area, Neuroscience, Aging, Head and Neck and Orthopaedics Sciences Department, Fondazione Policlinico Universitario Gemelli, Rome, Italy.
¹¹ Centro Sclerosi Multipla - Presidio ospedaliero di Gallarate - ASST Valle Olona, Gallarate, Italy.
¹² UOSD Centro di Riferimento Regionale Sclerosi Multipla - Dipartimento di Neuroscienze Policlinico Tor Vergata, Rome, Italy.
¹³ Department of Neurosciences, Reproductive Sciences and Odontostomatology, Multiple Sclerosis Centre, Federico II University, Naples, Italy.
¹⁴ Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health and Center of Excellence for Biomedical Research, University of Genova, Genoa, Italy.
¹⁵ IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
¹⁶ Department of Neuroimmunology and Neuromuscular Diseases, Neurological Institute C. Besta, IRCCS Foundation, Milan, Italy.
¹⁷ Neurology Unit, Azienda Sanitaria Univeristaria Integrata Clinica Neurologica, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Trieste, Trieste, Italy.
¹⁸ Department of Neuroscience, Città della Salute e della Scienza di Torino University Hospital, Turin, Italy.

PMID: 31452081
PMCID: PMC7007494
DOI: 10.1007/s13311-019-00776-7

Observational Study

Extending the Interval of Natalizumab Dosing: Is Efficacy Preserved?

Marinella Clerico et al. Neurotherapeutics. 2020 Jan.

. 2020 Jan;17(1):200-207.

doi: 10.1007/s13311-019-00776-7.

Authors

Affiliations

¹ Clinical and Biological Sciences Department, Neurology Unit, University of Torino, San Luigi Gonzaga Hospital, Regione Gonzole, 10, Orbassano, 10043, Turin, Italy.
² Clinical and Biological Sciences Department, Neurology Unit, University of Torino, San Luigi Gonzaga Hospital, Regione Gonzole, 10, Orbassano, 10043, Turin, Italy. sdemercanti@yahoo.it.
³ Department of Health Sciences, Section of Biostatistics, University of Genova, Genoa, Italy.
⁴ Multiple Sclerosis Center, Spedali Civili of Brescia, Presidio di Montichiari, Brescia, Italy.
⁵ Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy.
⁶ Clinic of Neurology, AOU - University of Campania "Luigi Vanvitelli", Naples, Italy.
⁷ Neurological Clinic and Multiple Sclerosis Centre of "AORN A. Cardarelli", Naples, Italy.
⁸ Neurology Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy.
⁹ Multiple Sclerosis Center, Binaghi Hospital, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
¹⁰ Multiple Sclerosis Center, Neuroscience Area, Neuroscience, Aging, Head and Neck and Orthopaedics Sciences Department, Fondazione Policlinico Universitario Gemelli, Rome, Italy.
¹¹ Centro Sclerosi Multipla - Presidio ospedaliero di Gallarate - ASST Valle Olona, Gallarate, Italy.
¹² UOSD Centro di Riferimento Regionale Sclerosi Multipla - Dipartimento di Neuroscienze Policlinico Tor Vergata, Rome, Italy.
¹³ Department of Neurosciences, Reproductive Sciences and Odontostomatology, Multiple Sclerosis Centre, Federico II University, Naples, Italy.
¹⁴ Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health and Center of Excellence for Biomedical Research, University of Genova, Genoa, Italy.
¹⁵ IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
¹⁶ Department of Neuroimmunology and Neuromuscular Diseases, Neurological Institute C. Besta, IRCCS Foundation, Milan, Italy.
¹⁷ Neurology Unit, Azienda Sanitaria Univeristaria Integrata Clinica Neurologica, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Trieste, Trieste, Italy.
¹⁸ Department of Neuroscience, Città della Salute e della Scienza di Torino University Hospital, Turin, Italy.

PMID: 31452081
PMCID: PMC7007494
DOI: 10.1007/s13311-019-00776-7

Abstract

Extending the natalizumab interval after the 24th administration could reduce the risk of progressive multifocal leukoencephalopathy (PML). The objective is to evaluate the noninferiority of the efficacy of an extended interval dosing (EID) compared with the standard interval dosing (SID) of natalizumab. It is an observational, multicenter (14 Italian centers), retrospective cohort study, starting from the 24th natalizumab infusion to the loss of follow-up or 2 years after baseline. Patients were grouped in 2 categories according to the mean number of weeks between doses: < 5 weeks, SID; ≥ 5 weeks, EID. Three hundred and sixty patients were enrolled. Median dose interval (MDI) following 24th infusion was 4.7 weeks, with a bimodal distribution (modes at 4 and 6 weeks). Two hundred and sixteen patients were in the SID group (MDI = 4.3 weeks) and 144 in the EID group (MDI 6.2 weeks). Annualized relapse rate was 0.060 (95% CI = 0.033-0.087) in the SID group and 0.039 (95% CI = 0.017-0.063) in the EID group. The non-inferiority of EID versus SID was satisfied. In conclusion, there is no evidence of a reduced efficacy of natalizumab in an EID setting. This observation confirms previous results and together with the emerging evidence of a reduced risk of PML associated to an EID, supports the need of a randomized study to assess the need to change the standard of the natalizumab dosing schedule.

Keywords: Multiple sclerosis; efficacy; extended dose; natalizumab; progressive multifocal leukoencephalopathy.

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Figures

**Fig. 1**
Annualized relapse rate over 2 years according to interval dose. ITT = intention-to-treat, PP = per-protocol, SID = standard interval dose, EID = extended interval dose

**Fig. 2**
Time to first relapse according to interval dose. Solid line: standard interval dose; dash line: extended interval dose

See this image and copyright information in PMC

References

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Extending the Interval of Natalizumab Dosing: Is Efficacy Preserved?

Affiliations

Extending the Interval of Natalizumab Dosing: Is Efficacy Preserved?

Authors

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Abstract

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