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Guidelines on the clinical use for the detection of neutralizing antibodies (NAbs) to IFN beta in multiple sclerosis therapy: report from the Italian Multiple Sclerosis Study group

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An Erratum to this article was published on 02 February 2014

Abstract

Interferon beta (IFNβ) was the first specific disease-modifying treatment licensed for relapsing-remitting multiple sclerosis, and is still one of the most commonly prescribed treatments. A strong body of evidence supports the effectiveness of IFNβ preparations in reducing the annual relapse rate, magnetic resonance (MRI) disease activity and disease progression. However, the development of binding/neutralizing antibodies (BAbs/NAbs) during treatment negatively affects clinical and MRI outcomes. Therefore, guidelines for the clinical use for the detection of NAbs in MS may result in better treatment of these patients. In October 2012, a panel of Italian neurologists from 17 MS clinics convened in Milan to review and discuss data on NAbs and their clinical relevance in the treatment of MS. In this paper, we report the panel’s recommendations for the use of IFNβ Nabs detection in the early identification of IFNβ non-responsiveness and the management of patients on IFNβ treatment in Italy, according to a model of therapeutically appropriate care.

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References

  1. Trojano M, Pellegrini F, Fuiani A, Paolicelli D, Zipoli V, Zimatore GB, Di Monte E, Portaccio E, Lepore V, Livrea P, Amato MP (2007) New natural history of interferon-beta-treated relapsing multiple sclerosis. Ann Neurol 61:300–306

    Article  CAS  PubMed  Google Scholar 

  2. Bertolotto A, Malucchi S, Sala A, Orefice G, Carrieri PB, Capobianco M, Milano E, Melis F, Giordana MT (2002) Differential effects of three interferon betas on neutralising antibodies in patients with multiple sclerosis: a follow up study in an independent laboratory. J Neurol Neurosurg Psychiatry 73:148–153

    Article  CAS  PubMed  Google Scholar 

  3. Sorensen PS, Deisenhammer F, Duda P, Hohlfeld R, Myhr KM, Palace J, Polman C, Pozzilli C, Ross C (2005) Guidelines on use of anti-IFN beta antibody measurements in multiple sclerosis: report of an EFNS Task Force on IFN-beta antibodies in multiple sclerosis. Eur J Neurol 12:817–827

    Article  CAS  PubMed  Google Scholar 

  4. Polman CH, Bertolotto A, Deasenhammer F, Giovannoni G, Hartung HP, Hemmer B, Killestein J, McFarland HF, Oger J, Pachner AR, Petkau J, Reder AT, Reingold SC, Schellekeng H, Sorensen PS (2010) Recommendations for clinical use of data on neutralizing antibodies to interferon-beta therapy in multiple sclerosis. Lancet Neurol 9(7):740–750

    Article  CAS  PubMed  Google Scholar 

  5. Paolicelli D, D’Onghia M, Pellegrini F, Direnzo V, Iaffaldano P, Lavolpe V, Trojano M (2013) The impact of neutralizing antibodies on the risk of disease worsening in interferon b-treated relapsing multiple sclerosis: a 5 year post-marketing study. J Neurol 260(6):1562–1568

    Article  CAS  PubMed  Google Scholar 

  6. Noyes K, Bajorska A, Chapel A, Schwid SR, Mehta LR, Weinstock-Guttman B, Holloway RG, Dick AW (2011) Cost-effectiveness of disease modifying therapy for multiple sclerosis. A population-based study. Neurology 77:355–363

    Article  CAS  PubMed  Google Scholar 

  7. Brook RH (1994) Appropriateness of care: the new frontier. BMJ 308:218–219

    Article  CAS  PubMed  Google Scholar 

  8. Fuchs VR (2011) The doctor’s dilemma—what is “appropriate” care ? NEJM 365(7):585–587

    Article  CAS  PubMed  Google Scholar 

  9. Rio J, Comabella M, Montalban X (2009) Predicting responders to therapies for multiple sclerosis. Nat Rev Neurol 5(10):533–560

    Article  Google Scholar 

  10. Sormani MP, De Stefano N (2013) Defining and scoring response to IFN β in multiple sclerosis. Nat Rev Neurol 9:504–512

    Article  CAS  PubMed  Google Scholar 

  11. Hardman JG, Limbird LE, Gilman AG (1996) The pharmacological basis of therapeutics. McGraw-Hill, New York

  12. Malucchi S, Gilli F, Caldano M, Sala A, Capobianco M, di Sapio A, Granieri L, Bertolotto A (2011) One-year evaluation of factors affecting the biological activity of interferon beta in multiple sclerosis patients. J Neurol 258:895–903

    Article  CAS  PubMed  Google Scholar 

  13. Bertolotto A, Gilli F (2008) Interferon-beta responders and non-responders. A biological approach. Neurol Sci 29:S216–S217

    Article  PubMed  Google Scholar 

  14. Sbardella E, Tomassini V, Gasperini C, Bellomi F, Cefano LA, Morra VB, Antonelli G, Pozzilli C (2009) Neutralizing antibodies explain the poor clinical response to interferon beta in a small proportion of patients with Multiple Sclerosis: retrospective study. BMC Neurol 9:54

    Article  PubMed Central  PubMed  Google Scholar 

  15. Rudick RA, Polman CH (2009) Current approaches to the identification and management of breakthrough disease in patients with multiple sclerosis. Lancet Neurol 8(6):545–559

    Article  PubMed  Google Scholar 

  16. Hesse D, Krakauer M, Lund H, Sondegaard HB, Langkilde A, Ryder LP, Sorensen PS, Sellebjerg F (2010) Breakthrough disease during interferon-beta therapy in MS: no signs of impaired biologic response. Neurol 4;74(18):1455–1462

    Google Scholar 

  17. Steinberg SC, Faris RJ, Chang CF, Cham A, Tankersley MA (2010) Impact of adherence to interferons in the treatment of multiple sclerosis: a non-experimental, retrospective, cohort study. Clin Drug Investig 30(2):89–100

    Article  CAS  PubMed  Google Scholar 

  18. Kobelt G, Berg J, Lindgren P, Battaglia M, Lucioni C, Uccelli A (2006) Costs and quality of life of multiple sclerosis in Italy. Eur J Health Econ 7(Suppl 2):S45–S54

    Article  PubMed  Google Scholar 

  19. Goldberg LD, Edwards NC, Fincher C, Doan QV, Al-Sabbagh A, Meletiche DM (2009) Comparing the cost-effectiveness of disease-modifying drugs for the first-line treatment of relapsing-remitting multiple sclerosis. J Manag Care Pharm 15(7):543–555

    PubMed  Google Scholar 

  20. Hegen H, Millonig A, Bertolotto A, Comabella M, Giovanonni G, Guger M, Hoelzl M, Khalil M, Killestein J, Lindberg R, Malucchi S, Mehling M, Montalban X, Polman C, Rudzki D, Schautzer F, Sellebjerg F, Sørensen P, Deisenhammer F (2013) Early detection of neutralizing antibodies to interferon-beta in multiple sclerosis patients: binding antibodies predict neutralizing antibody development. Mult Scler [Epub ahead of print]

  21. Sorensen PS, Koch-Henriksen N, Ross C, Clemmesen KM, Bendtsen K (2005) Appearance and disappearance of neutralizing antibodies during interferon-beta therapy. Neurology 65(1):33–39

    Article  CAS  PubMed  Google Scholar 

  22. Malucchi S, Sala A, Gilli F, Bottero R, Di Sapio A, Capobianco M, Bertolotto A (2004) Neutralizing antibodies reduce the efficacy of beta IFN during treatment of multiple sclerosis. Neurology 62:2031–2037

    Article  CAS  PubMed  Google Scholar 

  23. Creeke PI, Farrell RA (2013) Clinical testing for neutralizing antibodies to interferon-β in multiple sclerosis. Ther Adv Neurol Disord 6(1):3–17

    Article  PubMed Central  PubMed  Google Scholar 

  24. Sorensen PS, Ross C, Clemmensen KM, Bendtzen K, Frederiksen JL, Jensen K, Kristensen O, Petersen T, Rasmussen S, Ravnoborg M, Stenager E, Koch-Henriksen N, the Danish Multiple Sclerosis Study Group (2003) Clinical importance of neutralizing antibodies against interferon beta in patients with relapsing-remitting multiple sclerosis. Lancet 362:1184–1191

    Article  CAS  PubMed  Google Scholar 

  25. Farrell RA, Marta M, Gaeguta AJ, Souslova V, Giovannoni G, Creeke PI (2012) Understanding drug resistance to biologic therapy. Development of resistance to biologic therapies with reference to IFN-β. Rheumatology 51(4):590–599

    Article  CAS  PubMed  Google Scholar 

  26. Bertolotto A, Malucchi S, Milano E, Castello A, Capobianco M, Mutani R (2000) Interferon beta neutralizing antibodies in multiple sclerosis: neutralizing activity and cross-reactivity with three different preparations. Immunopharmacology 48:95–100

    Article  CAS  PubMed  Google Scholar 

  27. Barnard JG, Babcock K, Carpenter JF (2012) Characterization and quantitation of aggregates and particles in interferon-β products: Potential links between product quality attributes and immunogenicity. J Pharm Sci Dec 11. doi:10.1002/jps.23415. [Epub ahead of print]

  28. Hoffmann S, Cepok S, Grummel V, Lehmann-Horn K, Hackermüller J, Stadler PF, Hartung HP, Berthele A, Deisenhammer F, Wassmuth R, Hemmer B (2008) HLA-DRB1*0401 and HLA-DRB1*0408 are strongly associated with the development of antibodies against interferon-beta therapy in multiple sclerosis. Am J Hum Genet 83(2):219–227

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Deisenhammer F, Schellekens H, Bertolotto A (2004) Measurement of neutralizing antibodies to interferon beta in patients with multiple sclerosis. J Neurol 251(Suppl 2):II31–II39

    PubMed  Google Scholar 

  30. Bertolotto A, Deisenhammer F, Gallo P, Soelberg Sorensen P (2004) Immunogenicity of interferon beta. Differences among products. J Neurol 251(suppl 2):II15–II24

    PubMed  Google Scholar 

  31. Comi G, De Stefano N, Freedman MS, Barkhof F, Polman CH, Kitdehaag BM, Casset-Semanaz F, Hennessy B, Moraga MS, Rocak S, Stubinski B, Kappos L (2012) Comparison of two dosing frequencies of subcutaneous interferon beta-1a in patients with a first clinical demyelinating event suggestive of multiple sclerosis (REFLEX): a phase 3 randomized controlled trial. Lancet Neurol 11(1):33–41

    Article  CAS  PubMed  Google Scholar 

  32. Cutter G (2003) Statistical issues in neutralizing antibodies. Neurology 61(Suppl 5):S38–S39

    Article  PubMed  Google Scholar 

  33. Hesse D, Sørensen PS (2007) Using measurements of neutralizing antibodies: the challenge of IFN-beta therapy. Eur J Neurol 14(8):850–859

    Article  CAS  PubMed  Google Scholar 

  34. The IFNB Multiple Sclerosis Study Group and the University of British Columbia MS/MRI Analysis Group (1996) Neutralizing antibodies during treatment of multiple sclerosis with interferon beta-1b: experience during the first 3 years. Neurology 47:889–894

    Article  Google Scholar 

  35. The PRISMS (Prevention of Relapses and Disability by Interferon-β-1a Subcutaneously in Multiple Sclerosis) Study Group and the University of British Columbia MS/MRI Analysis Group (2001) PRISMS-4: long-term efficacy of interferon-β-1a in relapsing MS. Neurology 56:1628–1636

    Article  Google Scholar 

  36. Kappos L, Clanet M, Sandberg W, Radue EW, Hartung HP, Hohlfeld R, Xu J, bennett D, Sandrock A, Goelz S and European Interferon beta-1a IM Dose-Comparison Study Investigators (2005) Neutralizing antibodies and efficacy of interferon β-1a: a 4 year controlled study. Neurology 65:40–47

    Article  Google Scholar 

  37. Sormani MP, Bruzzi P (2013) MRI lesions as a surrogate for relapses in multiple sclerosis: a meta-analysis of randomised trials. Lancet Neurol 12(7):669–676

    Article  PubMed  Google Scholar 

  38. Francis GS, Rice GP, Alsop JC, PRISMS Study Group (2005) Interferon beta-1a in MS: results following development of neutralizing antibodies in PRISMS. Neurology 65:48–55

    Article  CAS  PubMed  Google Scholar 

  39. Rudick RA, Simonian NA, Alam JA, Campion M, Scaramucci JO, Jones W, Coats ME, Goodkin DE, Weinstock-Guttman B, Herndon RM, Mass MK, Richert JR, Salazar AM, Munschauer FF 3rd, Cookfair DL, Simon JH, Jacobs LD (1998) Incidence and significance of neutalizing antibodies to interferon beta 1a in multiple sclerosis. Neurology 50:1266–1272

    Article  CAS  PubMed  Google Scholar 

  40. Deisenhammer F, Reindel M, Harvey J, Gasse T, Dilitz E, Berger T (1999) Bioavailability of interferon beta 1b in MS patients with and without neutralizing antibodies. Neurology 52:1239–1243

    Article  CAS  PubMed  Google Scholar 

  41. Bertolotto A, Gilli F, Sala A, Audano L, Castello A, Magliola U, Melis F, Giordana MT (2001) Evaluation of bioavalability of three types of IFN beta in multiple sclerosis patients by a new quantitative-competitive-PCR method for MxA quantification. J Immunol Methods 256:141–152

    Article  CAS  PubMed  Google Scholar 

  42. Pachner A, Narayan K, Price N, Hurd M, Dail D (2003) MxA gene expression analysis as an interferon-beta bioactivity measurement in patients with multiple sclerosis and the identification of antibody-mediated decreased bioactivity. Mol Diagn 7:17–25

    PubMed  Google Scholar 

  43. Wandinger KP, Lünemann JD, Wengert O, Bellmann-Strobl J, Aktas O, Weber A, Grundstrom E, Ehrlich S, Wernecke KD, Volk HD, Zipp F (2003) TNF-related apoptosis inducing ligand (TRAIL) as a potential response marker for interferon-beta treatment in multiple sclerosis. Lancet 361:2036–2043

    Article  CAS  PubMed  Google Scholar 

  44. Gilli F, Marnetto F, Caldano M, Sala A, Malucchi S, Capobianco M, Bertolotto A (2006) Biological markers of IFNβ therapy: comparison among interferon-stimulated-genes MxA, TRAIL, and XAF-1. Mult Scler 12:1–11

    Article  Google Scholar 

  45. Pachner AR, Warth JD, Pace A, Goelz S, INSIGHT investigators (2009) Effect of neutralizing antibodies on biomarker responses to interferon beta. The INSIGHT study. Neurology 73:1493–1500

    Article  CAS  PubMed  Google Scholar 

  46. Sellebjerg F, Krakauer M, Hesse D, Ryder LP, Alsing I, Jensen PE, Koch-Henriksen N, Svejgaard A, Soelberg Sørensen P (2009) Identification of new sensitive biomarkers for the in vivo response to interferon-beta treatment in multiple sclerosis using DNA-array evaluation. Eur J Neurol 16(12):1291–1298

    Article  CAS  PubMed  Google Scholar 

  47. Hesse D, Sellbjerg F, Sorensen PS (2009) Absence of MxA induction by interferon β in patients with MS reflects complete loss of bioactivity. Neurology 73:372–377

    Article  CAS  PubMed  Google Scholar 

  48. Zanotti C, Ghidini C, Lamorgese C, Caimi L, Capra R, Imberti L (2010) Transfer of myxovirus-protein-A mRNA assay for interferon-β bioactivity measurement in multiple sclerosis patients to routine laboratory practice. A 4-year experience. Clin Chem Lab Med 48(9):1235–1238

    Article  CAS  PubMed  Google Scholar 

  49. Malucchi S, Gilli F, Caldano M, Marnetto F, Valentino P, Granieri L, Sala A, Capobianco M, Bertolotto A (2008) Predictive markers for response to interferon therapy in patients with multiple sclerosis. Neurology 70(13 Pt 2):119–127

    Google Scholar 

  50. Van der Voort, LF, Vennegoor A, Visser A, Knol DL, Kitdehaag BM, Barkhof F, Oudejans CB, Polman CH, Killestein J (2010) Spontaneous MxA mRNA level predicts relapses in patients with recently diagnosed MS. Neurol 5,75(14):1228–1233

    Google Scholar 

  51. Bertolotto A, Gilli F, Sala A, Capobianco M, Malucchi S, Milano E, Melis F, Marnetto F, Linberg RL, Bottero R, Di Sapio A, Giordana MT (2003) Persistent neutralizing antibodies abolish the interferon β bioavailability in MS patients. Neurology 60:634–639

    Article  CAS  PubMed  Google Scholar 

  52. Capra R, Sottini A, Cordioli C, Serana F, Chiarini M, Caimi L, Padovani A, Bergamaschi R, Imberti L (2007) IFNbeta bioavailability in multiple sclerosis patients: MxA versus antibody-detecting assays. J Neuroimmunol 189(1–2):102–110

    Article  CAS  PubMed  Google Scholar 

  53. Fitzgerald S (2009) Antibodies block effect of interferon on MS. Neurology Today 9(15):14

    Article  Google Scholar 

  54. Secondary Progressive Efficacy Clinical Trial of Recombinant Interferon-beta-1a in MS (SPECTRIMS) Study Group (2001) Randomized controlled trial of interferon-beta-1a in secondary progressive MS: Clinical results. Neurology 56:1496–1504

    Article  Google Scholar 

  55. Panitch H, Goodin DS, Francis G, Chang P, Coyle PK, O’Connor P, Monaghan E, Li D, Weinshenker B for the EVIDENCE (Evidence of Interferon Dose-Response: European North American Comparative Efficacy) Study Group and the University of British Columbia MS/MRI Research Group (2002) Randomized, comparative study of interferonβ-1a treatment regimens in MS. The EVIDENCE Trial. Neurol 59:1496–1506

    Google Scholar 

  56. Durelli L, Verdun E, Barbero P, Bergui M, Versino E, Chezzi A, Montanari E, Zaffaroni M, the Independent COMparison of Interferon (INCOMIN) Trial Study Group (2002) Every-other-day interferon beta-1b versus once-weekly interferon beta-1a for multiple sclerosis: results of a 2-year prospective randomised multicentre study (INCOMIN). Lancet 359:1453–1460

    Article  CAS  PubMed  Google Scholar 

  57. Polman C, Kappos L, White R, Dahlke F, beckmann K, Pozzilli C, Thompson A, Petkau J, Miller D (2003) Neutralizing antibodies during treatment of secondary progressive MS with interferon beta-1b. Neurology 60:37–43

    Article  CAS  PubMed  Google Scholar 

  58. The North American Study Group on Interferon beta-1b in Secondary Progressive MS (2004) Interferon beta-1b in secondary progressive MS. Results from a 3-year controlled study. Neurology 3:1788–1795

    Article  Google Scholar 

  59. Hartung H-P, Freedman MS, Polman CH, Edan G, Kappos L, Miller DH, Montalban X, Barkhof F, Petkau J, White R, Sahajpal V, Knappertz V, Beckmann K, Lanius V, Sandbrink R, Pohl C, For the BENEFIT Study Group (2011) Interferon β-1b—neutralizing antibodies 5 years after clinically isolated syndrome. Neurology 77:835–843

    Article  CAS  PubMed  Google Scholar 

  60. Frank JA, Richert N, Bash C, Stone L, Calabresi PA, Lewis B, Stone R, Howard T, McFarland HF (2004) InterferonB-1b slows progression of atrophy in RRMS. Three-year follow-up in NAb and Nab patients. Neurology 62:719–725

    Article  CAS  PubMed  Google Scholar 

  61. Perini P, Calabrese M, Biasi G, Gallo P (2004) The clinical impact of interferon beta antibodies in relapsing-remitting MS. J Neurol 251:305–309

    Article  CAS  PubMed  Google Scholar 

  62. Tomassini V, Paolillo A, Russo P, Giugni E, Prosperini L, Gasperini C, Antonelli G, Bastianello S, Pozzilli C (2006) Predictors of long-term clinical response to interferon beta therapy in relapsing multiple sclerosis. J Neurol 253:287–293

    Article  CAS  PubMed  Google Scholar 

  63. Boz C, Oger J, Gibbs E, Grossberg SE (2007) Reduced effectiveness of long-term interferon-treatment on relapses in neutralizing antibody-positive multiple sclerosis patients: a Canadian multiple sclerosis clinic-based study. Mult Scler 13:1127–1137

    Article  CAS  PubMed  Google Scholar 

  64. Durelli L, Barbero P, Berqui M, Versino E, Bassano MA, Verdun E, Rivoiro C, Ferrero C, Picco E, Ripellino P, Giuliani G, Montanari E, Clerico M (2008) MRI activity and neutralising antibody as predictors of response to interferon b treatment in multiple sclerosis. J Neurol Neurosurg Psychiatry 79:646–651

    Article  CAS  PubMed  Google Scholar 

  65. Li DK, Zhao GJ, Paty DW, University of British Columbia MS/MRI Analysis Research Group, The SPRECTRIMS Study Group (2001) Randomized controlled trial of interferon-beta 1a in secondary progressive MS: MRI results. Neurology 56(11):1505–1513

    Article  CAS  PubMed  Google Scholar 

  66. Sato DK, Nakashima I, Fukazawa T, Shimizu Y, Tomizawa Y, Yokoyama K, Misu T, Creeke PI, Farrell R, Giovannoni G, Itoyama Y, Fujihara K, Aoki M (2012) Neutralizing antibodies are associated with a reduction of Interferon-b efficacy during the treatment of Japanese Multiple sclerosis patients. Tohoky J Exp Med 228:85–92

    Article  CAS  Google Scholar 

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Acknowledgments

This Consensus Paper, aimed at providing Italian neurologists with National Recommendations for anti-IFNβ NAb testing, is the result of a Consensus Meeting held in Milan on October 24, 2012. The Italian Society of Neurology (Società Italiana di Neurologia, SIN) was the official sponsor of the meeting. Biogen Idec Italia provided unrestricted support to the logistics of the meeting with no influence on the content of the manuscript.

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Authors and Affiliations

  1. Neurologia 2-CRESM, AOU San Luigi, Orbassano, Italy

    Antonio Bertolotto, Marco Capobianco & Simona Malucchi

  2. Section Neurosciences, Department NEUROFARBA, University of Florence, Florence, Italy

    Maria Pia Amato

  3. Departmento of Neuroscience, Rehabilitation, Ophtalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy

    Elisabetta Capello

  4. Centro Sclerosi Multipla, Spedali Civili, Brescia, Italy

    Ruggero Capra

  5. Centro Sclerosi Multipla, Università Tor Vergata, Rome, Italy

    Diego Centonze & Silvia Rossi

  6. Dipartimento di Neuroscienze E Imaging, Centro Sclerosi Multipla, Università “G. d’Annunzio” Chieti, Chieti, Italy

    Maria Di Ioia & Alessandra Lugaresi

  7. II Division of Neurology, Second University of Naples, Naples, Italy

    Antonio Gallo & Gioachino Tedeschi

  8. U.O. di Neurologia, Fondazione Istituto San Raffaele “G. Giglio” di Cefalù, Cefalù, Pa, Italy

    Luigi Grimaldi

  9. CREA, Spedali Civili di Brescia, Brescia, Italy

    Luisa Imberti

  10. MultipleSclerosis Center S.Andrea Hospital Dept. Neurology and Psychiatry, Sapienza University, Rome, Italy

    Chiara Mancinelli & Carlo Pozzilli

  11. Dipartimento Sanità Pubblica Medicina Clinica e Molecolare, Centro Sclerosi Multipla, ASL 8, Università di Cagliari, Cagliari, Italy

    Maria Giovanna Marrosu & Luigina Musu

  12. Neurological Department, San Raffaele Scientific Institute, Milan, Italy

    Lucia Moiola

  13. Divisione di Neurologia, Ospedale Civile di Fidenza, Parma, Italy

    Enrico Montanari

  14. Neurology and Department of Neurosciences, Mental Health and Sensory Organs, Centre for Experimental Neurological Therapies (CENTERS), Sapienza University, S. Andrea Hospital-site, Rome, Italy

    Silvia Romano & Marco Salvetti

  15. Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy

    Damiano Paolicelli & Maria Troiano

  16. Department of Neurosciences, University of Catania, Catania, Italy

    Francesco Patti

  17. U.O. di Neurologia, Dipartimento Neuroscienze/Riabilitazione, AOU di Ferrara, Ferrara, Italy

    Maria Rosaria Tola

  18. Centro Studi Sclerosi Multipla, Ospedale di Gallarate, Gallarate, Italy

    Mauro Zaffaroni

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  1. Antonio Bertolotto
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Correspondence to Simona Malucchi.

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Bertolotto, A., Capobianco, M., Amato, M.P. et al. Guidelines on the clinical use for the detection of neutralizing antibodies (NAbs) to IFN beta in multiple sclerosis therapy: report from the Italian Multiple Sclerosis Study group. Neurol Sci 35, 307–316 (2014). https://doi.org/10.1007/s10072-013-1616-1

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