Recent developments in interferon-based therapies for multiple sclerosis

Expert Opinion on Biological Therapy

Volumn 18, Issue 6, 2018, Pages 665-680

  Dumitrescu, Laura ^a,b   Constantinescu, Cris S ^c   Tanasescu, Radu ^a,b,c  

^a CAROL DAVILA UNIVERSITY OF MEDICINE AND PHARMACY   (Romania)

^b V Babes National Institute of Pathology   (Romania)

^c UNIVERSITY OF NOTTINGHAM   (United Kingdom)

Author keywords

immunomodulation; Interferon beta; multiple sclerosis; PEGylated

Indexed keywords

BETA INTERFERON;

ANTIVIRAL ACTIVITY; DRUG DELIVERY SYSTEM; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; DRUG RESPONSE; DRUG SAFETY; DRUG TOLERABILITY; ENDOGENOUS RETROVIRUS; EPSTEIN BARR VIRUS INFECTION; HUMAN; MULTIPLE SCLEROSIS; PATHOGENESIS; REVIEW; COMBINATION DRUG THERAPY; IMMUNOTHERAPY; PROCEDURES;

DRUG THERAPY, COMBINATION; HUMANS; IMMUNOTHERAPY; INTERFERON-BETA; MULTIPLE SCLEROSIS;

EID: 85048282659     PISSN: 14712598     EISSN: 17447682     Source Type: Journal    
DOI: 10.1080/14712598.2018.1462793     Document Type: Review

References (164)

1. Lublin FD, Reingold SC, Cohen JA, et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology. 2014 Jul 15;83(3):278–286.
2. Lublin FD, Reingold SC., Defining the clinical course of multiple sclerosis: results of an international survey. National multiple sclerosis society (USA) advisory committee on clinical trials of new agents in multiple sclerosis. Neurology. 1996 Apr;46(4):907–911.
3. Wingerchuk DM, Carter JL., Multiple sclerosis: current and emerging disease-modifying therapies and treatment strategies. Mayo Clinic Proc. 2014 Feb;89(2):225–240.
4. Filippini G, Del Giovane C, Vacchi L, et al. Immunomodulators and immunosuppressants for multiple sclerosis: a network meta-analysis. Cochrane Database Syst Rev. 2013 Jun;06(6):CD008933.
5. Fogarty E, Schmitz S, Tubridy N, et al. Comparative efficacy of disease-modifying therapies for patients with relapsing remitting multiple sclerosis: systematic review and network meta-analysis. Mult Scler Relat Disord. 2016 Sep;9:23–30.
6. Newsome SD, Kieseier BC, Liu S, et al. Peginterferon beta-1a reduces disability worsening in relapsing-remitting multiple sclerosis: 2-year results from ADVANCE. Ther Adv Neurol Disord. 2017 Jan;10(1):41–50.
7. Cree BA, Gourraud PA, Oksenberg JR, et al. Long-term evolution of multiple sclerosis disability in the treatment era. Ann Neurol. 2016 Oct;80(4):499–510.
8. Scolding N, Barnes D, Cader S, et al. Association of British Neurologists: revised (2015) guidelines for prescribing disease-modifying treatments in multiple sclerosis. Pract Neurol. 2015 Aug;15(4):273–279.
9. Kalincik T, Brown JWL, Robertson N, et al. Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting multiple sclerosis: a cohort study. Lancet Neurol. 2017 Apr;16(4):271–281.
10. Smith AL, Cohen JA, Hua LH. Therapeutic targets for multiple sclerosis: current treatment goals and future directions. Neurotherapeutics. 2017 Jun 26;14:952–960.
11. Montalban X, Gold R, Thompson AJ, et al. ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis. Eur J Paediatr Neurol. 2018 Feb;25(2):215–237.
12. Venci JV, Gandhi MA. Dimethyl fumarate (Tecfidera): a new oral agent for multiple sclerosis. Ann Pharmacother. 2013 Dec;47(12):1697–1702.
13. Mikol DD, Barkhof F, Chang P, et al. Comparison of subcutaneous interferon beta-1a with glatiramer acetate in patients with relapsing multiple sclerosis (the REbif vs Glatiramer Acetate in Relapsing MS Disease [REGARD] study): a multicentre, randomised, parallel, open-label trial. Lancet Neurol. 2008 Oct;7(10):903–914.
14. Cadavid D, Wolansky LJ, Skurnick J, et al. Efficacy of treatment of MS with IFNbeta-1b or glatiramer acetate by monthly brain MRI in the BECOME study. Neurology. 2009 Jun 9;72(23):1976–1983.
15. Tsivgoulis G, Katsanos AH, Grigoriadis N, et al. The effect of disease modifying therapies on disease progression in patients with relapsing-remitting multiple sclerosis: a systematic review and meta-analysis. PLoS One. 2015;10(12):e0144538.
16. Capobianchi MR, Uleri E, Caglioti C, et al. Type I IFN family members: similarity, differences and interaction. Cytokine Growth Factor Rev. 2015 Apr;26(2):103–111.
17. Lopez de Padilla CM, Niewold TB. The type I interferons: basic concepts and clinical relevance in immune-mediated inflammatory diseases. Gene. 2016 Jan 15;576(1 Pt 1):14–21.
18. Tao Y, Zhang X, Chopra M, et al. The role of endogenous IFN-beta in the regulation of Th17 responses in patients with relapsing-remitting multiple sclerosis. J Immunol. 2014 Jun 15;192(12):5610–5617.
19. Gough DJ, Messina NL, Clarke CJ, et al. Constitutive type I interferon modulates homeostatic balance through tonic signaling. Immunity. 2012 Feb 24;36(2):166–174.
20. Dafny N, Yang PB. Interferon and the central nervous system. Eur J Pharmacol. 2005 Oct 31;523(1–3):1–15.
21. Kasper LH, Reder AT. Immunomodulatory activity of interferon-beta. Ann Clin Transl Neurol. 2014 Aug;1(8):622–631.
22. Martin R, Sospedra M, Rosito M, et al. Current multiple sclerosis treatments have improved our understanding of MS autoimmune pathogenesis. Eur J Immunol. 2016 Sep;46(9):2078–2090.
23. Steinman L. Immunology of relapse and remission in multiple sclerosis. Annu Rev Immunol. 2014;32:257–281.
24. Reder AT, Feng X. How type I interferons work in multiple sclerosis and other diseases: some unexpected mechanisms. J Interferon Cytokine Res. 2014 Aug;34(8):589–599.
25. Tanasescu R, Midgley A, Robins RA, et al. Decreased interferon-beta induced STAT-4 activation in immune cells and clinical outcome in multiple sclerosis. Acta Neurol Scand. 20167;136:233–238.
26. Axtell RC, Raman C, Steinman L. Type I interferons: beneficial in Th1 and detrimental in Th17 autoimmunity. Clin Rev Allergy Immunol. 2013 Apr;44(2):114–120.
27. Kimbrough DJ, Fujihara K, Jacob A, et al. Treatment of neuromyelitis optica: review and recommendations. Mult Scler Relat Disord. 2012 Oct;1(4):180–187.
28. Trebst C, Jarius S, Berthele A, et al. Update on the diagnosis and treatment of neuromyelitis optica: recommendations of the Neuromyelitis Optica Study Group (NEMOS). J Neurol. 2014 Jan;261(1):1–16.
29. Comabella M, Lunemann JD, Rio J, et al. A type I interferon signature in monocytes is associated with poor response to interferon-beta in multiple sclerosis. Brain. 2009 Dec;132(Pt 12):3353–3365.
30. Ransohoff RM, Hafler DA, Lucchinetti CF. Multiple sclerosis-a quiet revolution. Nat Rev Neurol. 2015 Mar;11(3):134–142.
31. Feng X, Reder NP, Yanamandala M, et al. Type I interferon signature is high in lupus and neuromyelitis optica but low in multiple sclerosis. J Neurol Sci. 2012 Feb 15;313(1–2):48–53.
32. Annibali V, Mechelli R, Romano S, et al. IFN-beta and multiple sclerosis: from etiology to therapy and back. Cytokine Growth Factor Rev. 2015 Apr;26(2):221–228.
33. Feng X, Petraglia AL, Chen M, et al. Low expression of interferon-stimulated genes in active multiple sclerosis is linked to subnormal phosphorylation of STAT1. J Neuroimmunol. 2002 Aug;129(1–2):205–215.
34. Bornsen L, Romme Christensen J, Ratzer R, et al. Endogenous interferon-beta-inducible gene expression and interferon-beta-treatment are associated with reduced T cell responses to myelin basic protein in multiple sclerosis. PLoS One. 2015;10(3):e0118830.
35. Rizzo F, Giacomini E, Mechelli R, et al. Interferon-beta therapy specifically reduces pathogenic memory B cells in multiple sclerosis patients by inducing a FAS-mediated apoptosis. Immunol Cell Biol. 2016 Oct;94(9):886–894.
36. Comi G, Radaelli M, Soelberg Sorensen P. Evolving concepts in the treatment of relapsing multiple sclerosis. Lancet. 2017 Apr 01; 389(10076):1347–1356.
37. Dooley J, Pauwels I, Franckaert D, et al. Immunologic profiles of multiple sclerosis treatments reveal shared early B cell alterations. Neurol Neuroimmunol Neuroinflamm. 2016 Aug;3(4):e240.
38. Noronha A, Toscas A, Jensen MA. Interferon beta decreases T cell activation and interferon gamma production in multiple sclerosis. J Neuroimmunol. 1993 Jul;46(1–2):145–153.
39. Feldhaus B, Dietzel ID, Heumann R, et al. Effects of interferon-gamma and tumor necrosis factor-alpha on survival and differentiation of oligodendrocyte progenitors. J Soc Gynecol Investig. 2004 Feb;11(2):89–96.
40. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. The IFNB Multiple Sclerosis Study Group. Neurology. 1993 Apr;43(4);655–661.
41. Dubey D, Cano CA, Stuve O. Update on monitoring and adverse effects of first generation disease modifying therapies and their recently approved versions in relapsing forms of multiple sclerosis. Curr Opin Neurol. 2016 Jun;29(3):272–277.
42. Kieseier BC, Arnold DL, Balcer LJ, et al. Peginterferon beta-1a in multiple sclerosis: 2-year results from ADVANCE. Mult Scler. 2015 Jul;21(8):1025–1035.
43. Marziniak M, Meuth S. Current perspectives on interferon Beta-1b for the treatment of multiple sclerosis. Adv Ther. 2014 Sep;31(9):915–931.
44. Scagnolari C, Selvaggi C, Di Biase E, et al. In vitro assessment of the biologic activity of interferon beta formulations used for the treatment of relapsing multiple sclerosis. J Immunoassay Immunochem. 2014;35(3):288–299.
45. Liu C, Blumhardt LD. Randomized, double-blind, placebo-controlled study of subcutaneous interferon beta-1a in relapsing-remitting multiple sclerosis: a categorical disability trend analysis. Mult Scler. 2002 Feb;8(1):10–14.
46. Jacobs LD, Cookfair DL, Rudick RA, et al. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Ann Neurol. 1996 Mar;39(3):285–294.
47. Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group. Lancet. 1998 Nov 07;352(9139):1498–1504.
48. De Stefano N, Curtin F, Stubinski B, et al. Rapid benefits of a new formulation of subcutaneous interferon beta-1a in relapsing-remitting multiple sclerosis. Mult Scler. 2010 Jul;16(7):888–892.
49. Jacobs LD, Beck RW, Simon JH, et al. Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis CHAMPS Study Group. N Engl J Med. 2000 Sep 28;343(13):898–904.
50. Comi G, Filippi M, Barkhof F, et al. Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet. 2001 May 19;357(9268):1576–1582.
51. Kappos L, Polman CH, Freedman MS, et al. Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes. Neurology. 2006 Oct 10;67(7):1242–1249.
52. Kappos L, Freedman MS, Polman CH, et al. Long-term effect of early treatment with interferon beta-1b after a first clinical event suggestive of multiple sclerosis: 5-year active treatment extension of the phase 3 BENEFIT trial. Lancet Neurol. 2009 Nov;8(11):987–997.
53. Simon JH, Kinkel RP, Kollman C, et al. Ten-year follow-up of the ‘minimal MRI lesion’ subgroup from the original CHAMPS multiple sclerosis prevention trial. Mult Scler. 2015 Apr;21(4):415–422.
54. Comi G, De Stefano N, Freedman MS, et al. Subcutaneous interferon beta-1a in the treatment of clinically isolated syndromes: 3-year and 5-year results of the phase III dosing frequency-blind multicentre REFLEXION study. J Neurol Neurosurg Psychiatry. 2017 Apr;88(4):285–294.
55. Comi G, De Stefano N, Freedman MS, et al. 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 randomised controlled trial. Lancet Neurol. 2012 Jan;11(1):33–41.
56. Placebo-controlled multicentre randomised trial of interferon beta-1b in treatment of secondary progressive multiple sclerosis. European Study Group on interferon beta-1b in secondary progressive MS. Lancet. 1998 Nov 07;352(9139):1491–1497.
57. Li DK, Zhao GJ, Paty DW. Randomized controlled trial of interferon-beta-1a in secondary progressive MS: MRI results. Neurology. 2001 Jun 12; 56(11):1505–1513.
58. Panitch H, Miller A, Paty D, et al. Interferon beta-1b in secondary progressive MS: results from a 3-year controlled study. Neurology. 2004 Nov 23; 63(10):1788–1795.
59. Leary SM, Miller DH, Stevenson VL, et al. Interferon beta-1a in primary progressive MS: an exploratory, randomized, controlled trial. Neurology. 2003 Jan 14;60(1):44–51.
60. Tur C, Montalban X, Tintore M, et al. Interferon beta-1b for the treatment of primary progressive multiple sclerosis: five-year clinical trial follow-up. Arch Neurol. 2011 Nov;68(11):1421–1427.
61. Reuss R. PEGylated interferon beta-1a in the treatment of multiple sclerosis - an update. Biologics. 2013;7:131–138.
62. Hu X, Hang Y, Cui Y, et al. Population-based pharmacokinetic and exposure-efficacy analyses of peginterferon beta-1a in patients with relapsing multiple sclerosis. J Clin Pharmacol. 2017 Aug;57(8):1005–1016.
63. Hu X, Shang S, Nestorov I, et al. COMPARE: pharmacokinetic profiles of subcutaneous peginterferon beta-1a and subcutaneous interferon beta-1a over 2 weeks in healthy subjects. Br J Clin Pharmacol. 2016 Aug;82(2):380–388.
64. Hu X, Miller L, Richman S, et al. A novel PEGylated interferon beta-1a for multiple sclerosis: safety, pharmacology, and biology. J Clin Pharmacol. 2012 Jun;52(6):798–808.
65. Signori A, Gallo F, Bovis F, et al. Long-term impact of interferon or Glatiramer acetate in multiple sclerosis: A systematic review and meta-analysis. Mult Scler Relat Disord. 2016 Mar;6:57–63.
66. Freedman MS. Long-term follow-up of clinical trials of multiple sclerosis therapies. Neurology. 2011 Jan 04;76(1 Suppl 1):S26–34.
67. Palace J, Duddy M, Bregenzer T, et al. Effectiveness and cost-effectiveness of interferon beta and glatiramer acetate in the UK multiple sclerosis risk sharing scheme at 6 years: a clinical cohort study with natural history comparator. Lancet Neurol. 2015 May;14(5):497–505.
68. Kappos L, Edan G, Freedman MS, et al. The 11-year long-term follow-up study from the randomized BENEFIT CIS trial. Neurology. 2016;87(10):978–987.
69. Ebers GC, Traboulsee A, Li D, et al. Analysis of clinical outcomes according to original treatment groups 16 years after the pivotal IFNB-1b trial. J Neurol Neurosurg Psychiatry. 2010 Aug;81(8):907–912.
70. Goodin DS, Reder AT, Ebers GC, et al. Survival in MS: a randomized cohort study 21 years after the start of the pivotal IFNbeta-1b trial. Neurology. 2012 Apr 24;78(17):1315–1322.
71. Kuhle J, Hardmeier M, Disanto G, et al. A 10-year follow-up of the European multicenter trial of interferon beta-1b in secondary-progressive multiple sclerosis. Mult Scler. 2016 Apr;22(4):533–543.
72. Ingwersen J, Aktas O, Hartung HP. Advances in and algorithms for the treatment of relapsing-remitting multiple sclerosis. Neurotherapeutics. 2016 Jan;13(1):47–57.
73. Koch-Henriksen N, Sorensen PS, Christensen T, et al. A randomized study of two interferon-beta treatments in relapsing-remitting multiple sclerosis. Neurology. 2006 Apr 11;66(7):1056–1060.
74. Oliver BJ, Kohli E, Kasper LH. Interferon therapy in relapsing-remitting multiple sclerosis: a systematic review and meta-analysis of the comparative trials. J Neurol Sci. 2011 Mar 15;302(1–2):96–105.
75. Klawiter EC, Cross AH, Naismith RT. The present efficacy of multiple sclerosis therapeutics: is the new 66% just the old 33%? Neurology. 2009 Sep 22;73(12):984–990.
76. O’Connor P, Filippi M, Arnason B, et al. 250 microg or 500 microg interferon beta-1b versus 20 mg glatiramer acetate in relapsing-remitting multiple sclerosis: a prospective, randomised, multicentre study. Lancet Neurol. 2009 Oct;8(10):889–897.
77. Durelli L, Verdun E, Barbero P, et al. 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. 2002 Apr 27;359(9316):1453–1460.
78. Barbero P, Bergui M, Versino E, et al. Every-other-day interferon beta-1b versus once-weekly interferon beta-1a for multiple sclerosis (INCOMIN Trial) II: analysis of MRI responses to treatment and correlation with Nab. Mult Scler. 2006 Feb;12(1):72–76.
79. Schwid SR, Panitch HS. Full results of the Evidence of Interferon Dose-Response-European North American Comparative Efficacy (EVIDENCE) study: a multicenter, randomized, assessor-blinded comparison of low-dose weekly versus high-dose, high-frequency interferon beta-1a for relapsing multiple sclerosis. Clin Ther. 2007 Sep;29(9):2031–2048.
80. Hesse D, Sellebjerg F, Sorensen PS. Absence of MxA induction by interferon beta in patients with MS reflects complete loss of bioactivity. Neurology. 2009 Aug 04;73(5):372–377.
81. Bertolotto A, Capobianco M, Amato MP, 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. 2014 Feb;35(2):307–316.
82. 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. PRISMS-4: long-term efficacy of interferon-beta-1a in relapsing MS. Neurology. 2001 Jun 26;56(12):1628–1636.
83. Francis GS, Rice GP, Alsop JC. Interferon beta-1a in MS: results following development of neutralizing antibodies in PRISMS. Neurology. 2005 Jul 12;65(1):48–55.
84. Cohen BA, Rivera VM. PRISMS: the story of a pivotal clinical trial series in multiple sclerosis. Curr Med Res Opin. 2010 Apr;26(4):827–838.
85. Giovannoni G, Barbarash O, Casset-Semanaz F, et al. Safety and immunogenicity of a new formulation of interferon beta-1a (Rebif New Formulation) in a Phase IIIb study in patients with relapsing multiple sclerosis: 96-week results. Mult Scler. 2009 Feb;15(2):219–228.
86. Hegen H, Adrianto I, Lessard CJ, et al. Cytokine profiles show heterogeneity of interferon-beta response in multiple sclerosis patients. Neurol Neuroimmunol Neuroinflamm. 2016 Apr;3(2):e202.
87. Carlson RJ, Doucette JR, Knox K, et al. Pharmacogenomics of interferon-beta in multiple sclerosis: what has been accomplished and how can we ensure future progress? Cytokine Growth Factor Rev. 2015 Apr;26(2):249–261.
88. Bustamante MF, Morcillo-Suarez C, Malhotra S, et al. Pharmacogenomic study in patients with multiple sclerosis: responders and nonresponders to IFN-beta. Neurol Neuroimmunol Neuroinflamm. 2015 Oct;2(5):e154.
89. Comabella M, Sastre-Garriga J, Montalban X. Precision medicine in multiple sclerosis: biomarkers for diagnosis, prognosis, and treatment response. Curr Opin Neurol. 2016 Jun;29(3):254–262.
90. Balak DM, Hengstman GJ, Cakmak A, et al. Cutaneous adverse events associated with disease-modifying treatment in multiple sclerosis: a systematic review. Mult Scler. 2012 Dec;18(12):1705–1717.
91. Landi D, Albanese M, Buttari F, et al. Management of flu-like syndrome with cetirizine in patients with relapsing-remitting multiple sclerosis during therapy with interferon beta: results of a randomized, cross-over, placebo-controlled pilot study. PLoS One. 2017;12(7):e0165415.
92. Orefice NS, Alhouayek M, Carotenuto A, et al. Oral palmitoylethanolamide treatment is associated with reduced cutaneous adverse effects of interferon-beta1a and circulating proinflammatory cytokines in relapsing-remitting multiple sclerosis. Neurotherapeutics. 2016 Apr;13(2):428–438.
93. Fontana RJ, Hayashi P, Bonkovsky HL, et al. Presentation and outcomes with clinically apparent interferon beta hepatotoxicity. Dig Dis Sci. 2013 Jun;58(6):1766–1775.
94. Patten SB, Metz LM. Interferon beta-1 a and depression in relapsing-remitting multiple sclerosis: an analysis of depression data from the PRISMS clinical trial. Mult Scler. 2001 Aug;7(4):243–248.
95. Pietrosi G, Mandala L, Vizzini GB, et al. Fulminant hepatic failure and autoimmune disorders in patient with multiple sclerosis on interferon beta 1a: a fatal combination? Transpl Int. 2008 May;21(5):502–504.
96. Yoshida EM, Rasmussen SL, Steinbrecher UP, et al. Fulminant liver failure during interferon beta treatment of multiple sclerosis. Neurology. 2001 May 22;56(10):1416.
97. Yamazaki Y, Suzuki A, Hirayanagi K, et al. An autopsy case of fulminant hepatitis in a patient with multiple sclerosis treated by interferon-Beta-1a. Intern Med. 2017;56(14):1897–1901.
98. de Jong HJI, Kingwell E, Shirani A, et al. Evaluating the safety of beta-interferons in MS: A series of nested case-control studies. Neurology. 2017 Jun 13;88(24):2310–2320.
99. Vosoughi R, Marriott JJ. Thrombotic microangiopathy in Interferon Beta treated multiple sclerosis patients: review of literature and report of two new cases. Mult Scler Relat Disord. 2014 May;3(3):321–325.
100. Hunt D, Kavanagh D, Drummond I, et al. Thrombotic microangiopathy associated with interferon beta. N Engl J Med. 2014 Mar 27;370(13):1270–1271.
101. Gerischer LM, Siebert E, Janke O, et al. Favorable outcome of interferon-beta associated thrombotic microangiopathy following treatment with corticosteroids, plasma exchange and rituximab: A case report. Mult Scler Relat Disord. 2016 Nov;10:63–65.
102. Larochelle C, Grand’maison F, Bernier GP, et al. Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome in relapsing-remitting multiple sclerosis patients on high-dose interferon beta. Mult Scler. 2014 Nov;20(13):1783–1787.
103. Rodrigues S, Magro F, Soares J, et al. Case series: ulcerative colitis, multiple sclerosis, and interferon-beta 1a. Inflamm Bowel Dis. 2010 Dec;16(12):2001–2003.
104. Schott E, Paul F, Wuerfel JT, et al. Development of ulcerative colitis in a patient with multiple sclerosis following treatment with interferonβ 1a. World J Gastroenterol. 2007;13(26):3638–3640.
105. Amato MP, Portaccio E. Fertility, pregnancy and childbirth in patients with multiple sclerosis: impact of disease-modifying drugs. CNS Drugs. 2015 Mar;29(3):207–220.
106. Almas S, Vance J, Baker T, et al. Management of multiple sclerosis in the breastfeeding mother. Mult Scler Int. 2016;2016:1–10.
107. Hale TW, Siddiqui AA, Baker TE. Transfer of interferon beta-1a into human breastmilk. Breastfeed Med. 2012 Apr;7(2):123–125.
108. Chou IJ, Wang HS, Whitehouse WP, et al. Paediatric multiple sclerosis: update on diagnostic criteria, imaging, histopathology and treatment choices. Curr Neurol Neurosci Rep. 2016 Jul;16(7):68.
109. Banwell B, Reder AT, Krupp L, et al. Safety and tolerability of interferon beta-1b in pediatric multiple sclerosis. Neurology. 2006;66(4):472–476.
110. Shirani A, Zhao Y, Petkau J, et al. Multiple sclerosis in older adults: the clinical profile and impact of interferon Beta treatment. Biomed Res Int. 2015;2015:1–11.
111. Yeh EA, Waubant E, Krupp LB, et al. Multiple sclerosis therapies in pediatric patients with refractory multiple sclerosis. Arch Neurol. 2011 Apr;68(4):437–444.
112. Kappos L, Kuhle J, Multanen J, et al. Factors influencing long-term outcomes in relapsing-remitting multiple sclerosis: PRISMS-15. Factors influencing long-term outcomes in relapsing-remitting multiple sclerosis: PRISMS-15. J Neurol Neurosurg Psychiatry. 2015 Nov;86(11):1202–1207.
113. Uitdehaag B, Constantinescu C, Cornelisse P, et al. Impact of exposure to interferon beta-1a on outcomes in patients with relapsing-remitting multiple sclerosis: exploratory analyses from the PRISMS long-term follow-up study. Ther Adv Neurol Disord. 2011 Jan;4(1):3–14.
114. Menzin J, Caon C, Nichols C, et al. Narrative review of the literature on adherence to disease-modifying therapies among patients with multiple sclerosis. J Manag Care Pharm. 2013 Jan-Feb;19(1 Suppl A):S24–40.
115. Burks J, Marshall TS, Ye X. Adherence to disease-modifying therapies and its impact on relapse, health resource utilization, and costs among patients with multiple sclerosis. Clinicoecon Outcomes Res. 2017;9:251–260.
116. Bayas A, Ouallet JC, Kallmann B, et al. Adherence to, and effectiveness of, subcutaneous interferon beta-1a administered by RebiSmart(R) in patients with relapsing multiple sclerosis: results of the 1-year, observational SMART study. Expert Opin Drug Deliv. 2015 Aug;12(8):1239–1250.
117. Paolicelli D, Cocco E, Di Lecce V, et al. Exploratory analysis of predictors of patient adherence to subcutaneous interferon beta-1a in multiple sclerosis: TRACER study. Expert Opin Drug Deliv. 2016 Jun;13(6):799–805.
118. Krol M, de Voer G, Osowski U. Patient adherence to subcutaneous IFN beta-1a injections using the RebiSmart(R) injection device: a retrospective real-world study among Dutch and German patients with multiple sclerosis. Patient Prefer Adherence. 2017;11:1189–1196.
119. Goodin DS, Traboulsee A, Knappertz V, et al. Relationship between early clinical characteristics and long term disability outcomes: 16 year cohort study (follow-up) of the pivotal interferon beta-1b trial in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2012 Mar;83(3):282–287.
120. Portaccio E, Zipoli V, Siracusa G, et al. Response to interferon-beta therapy in relapsing-remitting multiple sclerosis: a comparison of different clinical criteria. Mult Scler. 2006 Jun;12(3):281–286.
121. Fisniku LK, Brex PA, Altmann DR, et al. Disability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosis. Brain. 2008 Mar;131(Pt 3):808–817.
122. Leray E, Yaouanq J, Le Page E, et al. Evidence for a two-stage disability progression in multiple sclerosis. Brain. 2010 Jul;133(Pt7):1900–1913.
123. Rio J, Castillo J, Rovira A, et al. Measures in the first year of therapy predict the response to interferon beta in MS. Mult Scler. 2009 Jul;15(7):848–853.
124. Sormani MP, Rio J, Tintore M, et al. Scoring treatment response in patients with relapsing multiple sclerosis. Mult Scler. 2013 Apr;19(5):605–612.
125. Sormani MP, Gasperini C, Romeo M, et al. Assessing response to interferon-beta in a multicenter dataset of patients with MS. Neurology. 2016 Jul 12;87(2):134–140.
126. Stangel M, Penner IK, Kallmann BA, et al. Towards the implementation of ‘no evidence of disease activity’ in multiple sclerosis treatment: the multiple sclerosis decision model. Ther Adv Neurol Disord. 2015 Jan;8(1):3–13.
127. Giovannoni G, Turner B, Gnanapavan S, et al. Is it time to target no evident disease activity (NEDA) in multiple sclerosis? Mult Scler Relat Disord. 2015;4(4):329–333.
128. Havrdova E, Galetta S, Hutchinson M, et al. Effect of natalizumab on clinical and radiological disease activity in multiple sclerosis: a retrospective analysis of the Natalizumab Safety and Efficacy in Relapsing-Remitting Multiple Sclerosis (AFFIRM) study. Lancet Neurol. 2009 Mar;8(3):254–260.
129. Kappos L, Havrdova E, Giovannoni G, et al. No evidence of disease activity in patients receiving daclizumab versus intramuscular interferon beta-1a for relapsing-remitting multiple sclerosis in the DECIDE study. Mult Scler. 2017 Nov;23(13):1736-1747.
130. Hauser SL, Bar-Or A, Comi G, et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017 Jan 19;376(3):221–234.
131. Arnold DL, Calabresi PA, Kieseier BC, et al. Effect of peginterferon beta-1a on MRI measures and achieving no evidence of disease activity: results from a randomized controlled trial in relapsing-remitting multiple sclerosis. BMC Neurol. 2014 Dec 31;14:240.
132. Rotstein DL, Healy BC, Malik MT, et al. Evaluation of no evidence of disease activity in a 7-year longitudinal multiple sclerosis cohort. JAMA Neurol. 2015 Feb;72(2):152–158.
133. Damasceno A, Damasceno BP, Cendes F. No evidence of disease activity in multiple sclerosis: implications on cognition and brain atrophy. Mult Scler. 2016 Jan;22(1):64–72.
134. Paul F. Pathology and MRI: exploring cognitive impairment in MS. Acta Neurol Scand. 2016 Sep;134 Suppl 200(Suppl 200):24–33.
135. Berkovich R, Bakshi R, Amezcua L, et al. Adrenocorticotropic hormone versus methylprednisolone added to interferon beta in patients with multiple sclerosis experiencing breakthrough disease: a randomized, rater-blinded trial. Ther Adv Neurol Disord. 2017 Jan;10(1):3–17.
136. Lublin FD, Cofield SS, Cutter GR, et al. Randomized study combining interferon and glatiramer acetate in multiple sclerosis. Ann Neurol. 2013 Mar;73(3):327–340.
137. Sorensen PS, Mellgren SI, Svenningsson A, et al. NORdic trial of oral Methylprednisolone as add-on therapy to Interferon beta-1a for treatment of relapsing-remitting Multiple Sclerosis (NORMIMS study): a randomised, placebo-controlled trial. Lancet Neurol. 2009 Jun;8(6):519–529.
138. Ravnborg M, Sorensen PS, Andersson M, et al. Methylprednisolone in combination with interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN study): a multicentre, double-blind, randomised, placebo-controlled, parallel-group trial. Lancet Neurol. 2010 Jul;9(7):672–680.
139. Pozzilli C, De Giglio L, Barletta VT, et al. Oral contraceptives combined with interferon beta in multiple sclerosis. Neurol Neuroimmunol Neuroinflamm. 2015 Aug;2(4):e120.
140. Paul F, Waiczies S, Wuerfel J, et al. Oral high-dose atorvastatin treatment in relapsing-remitting multiple sclerosis. PLoS One. 2008 Apr 9;3(4):e1928.
141. Lanzillo R, Orefice G, Quarantelli M, et al. Atorvastatin combined to interferon to verify the efficacy (ACTIVE) in relapsing-remitting active multiple sclerosis patients: a longitudinal controlled trial of combination therapy. Mult Scler. 2010 Apr;16(4):450–454.
142. Sorensen PS, Lycke J, Eralinna JP, et al. Simvastatin as add-on therapy to interferon beta-1a for relapsing-remitting multiple sclerosis (SIMCOMBIN study): a placebo-controlled randomised phase 4 trial. Lancet Neurol. 2011 Aug;10(8):691–701.
143. Lanzillo R, Quarantelli M, Pozzilli C, et al. No evidence for an effect on brain atrophy rate of atorvastatin add-on to interferon beta1b therapy in relapsing-remitting multiple sclerosis (the ARIANNA study). Mult Scler. 2016 Aug;22(9):1163–1173.
144. Hernandez L, Guo S, Kinter E, et al. Cost-effectiveness analysis of peginterferon beta-1a compared with interferon beta-1a and glatiramer acetate in the treatment of relapsing-remitting multiple sclerosis in the United States. J Med Econ. 2016 Jul;19(7):684–695.
145. Wang KC, Lin KH, Lee TC, et al. Poor responses to interferon-beta treatment in patients with neuromyelitis optica and multiple sclerosis with long spinal cord lesions. PLoS One. 2014;9(6):e98192.
146. Harmel J, Ringelstein M, Ingwersen J, et al. Interferon-beta-related tumefactive brain lesion in a Caucasian patient with neuromyelitis optica and clinical stabilization with tocilizumab. BMC Neurol. 2014 Dec 17;14:247.
147. Oji S, Nicolussi EM, Kaufmann N, et al. Experimental neuromyelitis optica induces a Type I interferon signature in the spinal cord. PLoS One. 2016;11(3):e0151244.
148. HuangFu WC, Liu J, Harty RN, et al. Cigarette smoking products suppress anti-viral effects of Type I interferon via phosphorylation-dependent downregulation of its receptor. FEBS Lett. 2008 Sep 22;582(21–22):3206–3210.
149. Petersen ER, Oturai AB, Koch-Henriksen N, et al. Smoking affects the interferon beta treatment response in multiple sclerosis. Neurology. 2018;90(7):e593–e600.
150. Tanasescu R, Constantinescu CS, Tench CR, et al. Smoking cessation and the reduction of disability progression in Multiple Sclerosis: a cohort study. Nicotine Tob Res. 2018 Apr 2;20(5):589-595.
151. Hedstrom AK, Ryner M, Fink K, et al. Smoking and risk of treatment-induced neutralizing antibodies to interferon beta-1a. Mult Scler. 2014 Apr;20(4):445–450.
152. Teran-Cabanillas E, Montalvo-Corral M, Caire-Juvera G, et al. Decreased interferon-alpha and interferon-beta production in obesity and expression of suppressor of cytokine signaling. Nutrition. 2013 Jan;29(1):207–212.
153. Kvistad SS, Myhr KM, Holmoy T, et al. Body mass index influence interferon-beta treatment response in multiple sclerosis. J Neuroimmunol. 2015 Nov 15;288:92–97.
154. Koudriavtseva T. Body mass index and interferon-beta efficacy (and safety) in multiple sclerosis. J Neurol Sci. 2016 Dec 15;371:79–80.
155. Fitzgerald KC, Munger KL, Kochert K, et al. Association of vitamin D levels with multiple sclerosis activity and progression in patients receiving interferon beta-1b. JAMA Neurol. 2015 Dec;72(12):1458–1465.
156. Rotstein DL, Healy BC, Malik MT, et al. Effect of vitamin D on MS activity by disease-modifying therapy class. Neurol Neuroimmunol Neuroinflamm. 2015 Dec;2(6):e167.
157. Qu ZX, Dayal A, Jensen MA, et al. All-trans retinoic acid potentiates the ability of interferon beta-1b to augment suppressor cell function in multiple sclerosis. Arch Neurol. 1998 Mar;55(3):315–321.
158. Fahey AJ, Adrian Robins R, Constantinescu CS. Curcumin modulation of IFN-beta and IL-12 signalling and cytokine induction in human T cells. J Cell Mol Med. 2007 Sep-Oct;11(5):1129–1137.
159. Morandi E, Tanasescu R, Tarlinton RE, et al. The association between human endogenous retroviruses and multiple sclerosis: A systematic review and meta-analysis. PLoS One. 2017;12(2):e0172415.
160. Jacobs L, Salazar AM, Herndon R, et al. Intrathecally administered natural human fibroblast interferon reduces exacerbations of multiple sclerosis. Results of a multicenter, double-blind study. Arch Neurol. 1987 Jun;44(6):589–595.
161. Jacobs L, Salazar AM, Herndon R, et al. Multicentre double-blind study of effect of intrathecally administered natural human fibroblast interferon on exacerbations of multiple sclerosis. Lancet. 1986 Dec 20-27;2(8521–22):1411–1413.
162. Jacobs L, O’Malley J, Freeman A, et al. Intrathecal interferon reduces exacerbations of multiple sclerosis. Science. 1981 Nov 27;214(4524):1026–1028.
163. Milanese C, Salmaggi A, La Mantia L, et al. Double blind study of intrathecal beta-interferon in multiple sclerosis: clinical and laboratory results. J Neurol Neurosurg Psychiatry. 1990 Jul;53(7):554–557.
164. Ross TM, Martinez PM, Renner JC, et al. Intranasal administration of interferon beta bypasses the blood-brain barrier to target the central nervous system and cervical lymph nodes: a non-invasive treatment strategy for multiple sclerosis. J Neuroimmunol. 2004 Jun;151(1–2):66–77.