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Rituximab in the treatment of Neuromyelitis optica: a multicentre Italian observational study

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Abstract

Rituximab (RTX) efficacy in NMO is suggested by several case series. No consensus exists on optimal dosing strategies. At present the treatment schedules more frequently used are 375 mg/m2/week iv for 4 weeks (RTX-A) and 1000 mg iv twice, 2 weeks apart (RTX-B). Aim of this study is to confirm RTX efficacy and safety in the treatment of NMO and to evaluate whether a most favourable dosage regimen exists. Data on RTX-treated NMO patients were collected from 13 Italian Hospitals. 73 patients (64 F), were enlisted. RTX-A was administered in 42/73 patients, RTX-B in 31/73. Median follow-up was 27 months (range 7–106). Mean relapse rate in the previous year before RTX start was 2.2 ± 1.3 for RTX-A and 2.3 ± 1.2 for RTX-B. ARR in the first year of treatment was 0.8 ± 0.9 for RTX-A and 0.2 ± 0.4 for RTX-B, in the second year of treatment was 0.9 ± 1.5 for RTX-A and 0.4 ± 0.8 for RTX-B patients (p = 0.001 for the first year, ns (0.09) for the second year). RTX-B was more effective in delaying the occurrence of a relapse (HR 2.2 (95 % IC 1.08–4.53) p = 0.02). Adverse events were described in 19/73 patients (mainly urinary tract and respiratory infections, and infusion reactions). Two deaths were reported in severely disabled patients. Though with the limitations of an observational study, our data support RTX efficacy in NMO and suggest that high dose pulses might be more effective than a more fractioned dose.

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Author information

Authors and Affiliations

  1. Multiple Sclerosis Study Center, ASST Valle Olona, PO di Gallarate (VA), Italy

    Pietro Annovazzi, G. Comi & A. Ghezzi

  2. Regional MS Center, University Hospital S. Luigi Gonzaga, Orbassano (TO), Italy

    M. Capobianco

  3. Department of Neurology, Scientific Institute H. San Raffaele, University Vita-Salute, Milan, Italy

    L. Moiola, V. Martinelli & G. Comi

  4. Multiple Sclerosis Center, University of Catania, Catania, Italy

    F. Patti & J. Frau

  5. Department of Neurosciences Ophtalmology and Genetics, University of Genoa, Genoa, Italy

    A. Uccelli

  6. Department of Neurology I and neurorehabilitation, IRCCS Neuromed, Pozzilli (IS), Italy

    D. Centonze

  7. Department of Systems Medicine, University of Tor Vergata, Rome, Italy

    D. Centonze

  8. Department of Neurology, AO University of Padova, Padua, Italy

    P. Perini

  9. Departments of Neurological and Psychiatric Sciences, University of Bari, Bari, Italy

    C. Tortorella

  10. Department of Neurology and Psychiatry, Sapienza University, Rome, Italy

    L. Prosperini

  11. Department of Neurological Sciences, School of Medicine, Second University of Naples, Policlinico Federico II, Naples, Italy

    G. Lus

  12. Department of Neurosciences, Multiple Sclerosis Unit, General Hospital, “OORR”, Foggia, Italy

    A. Fuiani

  13. Multiple Sclerosis Center, Ospedale Misericordia e Dolce, Prato, Italy

    M. Falcini

Authors
  1. Pietro Annovazzi
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  2. M. Capobianco
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  3. L. Moiola
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  7. D. Centonze
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  8. P. Perini
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  13. M. Falcini
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  14. V. Martinelli
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Correspondence to Pietro Annovazzi.

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Conflicts of interest

Dr. Annovazzi received honoraria for advisory and speaking activities by Biogen, Merck Serono, Novartis, Sanofi Genzyme and TEVA. Dr. Capobianco speaking honoraria from Biogen, Almirall and Sanofi Genzyme; advisory board honoraria from Biogen and web paper production fees from Serono Foundation. Dr. Moiola received honoraria for speaking from Sanofi Aventis, Merck Serono and Biogen Idec. Prof. Patti received honoraria for advisory and speaking activities by Almirall, Bayer, Biogen, Merck Serono, Novartis Sanofi Genzyme and TEVA; He also received travel grants for congress participation by the same companies. He received unrestricted grants by the University of Catania, MIUR and FISM. Dr. Frau serves on scientific advisory boards for Biogen, received honoraria for speaking from Merck Serono and Teva, received research grant from Merck Serono. Prof. Uccelli received consultancy fees and support for travel expenses and participation to Congresses from Sanofi-Avemtis, Biogen, Merck-Serono, Novartis, and Roche. Prof. Centonze is an Advisory Board member of Almirall, Bayer Schering, Biogen, Genzyme, GW Pharmaceuticals, Merck-Serono, Novartis, Teva and received honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen Idec, Genzyme, GW Pharmaceuticals, Merck Serono, Novartis, Sanofi-Aventis, Teva. He is also an external expert consultant of the European Medicine Agency (EMA), and the principal investigator in clinical trials for Bayer Schering, Biogen Idec, Merck Serono, Mitsubishi, Novartis, Roche, Sanofi-aventis, Teva. His preclinical and clinical research was supported by grants from Bayer, Biogen, Merck Serono, Novartis e Teva. Dr. Perini received honoraria from Biogen, Serono, Novartis, Teva, Genzyme for lectures or advisory boards. Dr. Tortorella received honoraria for speaking from Biogen, Sanofi-Aventis, Serono and Bayer Schering, Teva, Genzyme and Novartis. Dr. Prosperini received honoraria for advisory and speaking activities by Biogen, Teva, Novartis, Sanofi Genzyme and research grant from FISM. Prof Lus received speaking honoraria and/or consultant fees from Biogen, Merck-Serono, Bayer, Novartis, Genzyme and Almirall. Dr. Fuiani received honoraria for speaking and advisory boards from Biogen and Sanofi-Aventis. Dr. Falcini reports no competing interests. Dr. Martinelli received honoraria for speaking and/or for consultancy and support for travel expenses and participation to Congresses from Bayer, Biogen-Idec, Merck-Serono, Novartis, Genzyme and Teva Pharma. Prof Comi serves on scientific advisory boards for Bayer Schering Pharma, Merck Serono, Teva, Sanofi Aventis, Novartis and Biogen-Idec; has received speaker honoraria from Teva, Sanofi Aventis, Serono Sumposia International Foundation, Biogen-Idec, Merck Serono, Novartis, Bayer Schering and Sanofi Aventis. Dr. Ghezzi serves on scientific advisory boards or as a consultant for Merck Serono, Novartis, Genzyme, Biogen Idec, Teva; received honoraria for speaking form Merck Serono, Serono Symposia International Foundation, Biogen Idec, Allmirall, Genzyme, Teva, and Novartis.

Ethical standard

The study was approved by the Ethical Committee of the coordinating centre in Gallarate Hospital (VA), Italy. The study was conducted complying with Helsinki Declaration.

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Annovazzi, P., Capobianco, M., Moiola, L. et al. Rituximab in the treatment of Neuromyelitis optica: a multicentre Italian observational study. J Neurol 263, 1727–1735 (2016). https://doi.org/10.1007/s00415-016-8188-y

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