Requirement for safety monitoring for approved multiple sclerosis therapies: an overview

During the last two decades, treatment options for patients with multiple sclerosis (MS) have broadened tremendously. All agents that are currently approved for clinical use have potential side effects, and a careful risk–benefit evaluation is part of a decision algorithm to identify the optimal treatment choice for an individual patient. Whereas glatiramer acetate and interferon beta preparations have been used in MS for decades and have a proven safety record, more recently approved drugs appear to be more effective, but potential risks might be more severe. The potential complications of some novel therapies might not even have been identified to their full extent. This review is aimed at the clinical neurologist in that it offers insights into potential adverse events of each of the approved MS therapeutics: interferon beta, glatiramer acetate, mitoxantrone, natalizumab, fingolimod and teriflunomide, as well as recently approved therapeutics such as dimethyl fumarate and alemtuzumab. It also provides recommendations for monitoring the different drugs during therapy in order to avoid common side effects.

[1]  D. Jayne,et al.  SUMMARY OF PRODUCT CHARACTERISTICS , 2014 .

[2]  Jeffrey A. Cohen,et al.  Defining the clinical course of multiple sclerosis: the 2013 revisions. , 2014, Neurology.

[3]  A. Winkelmann,et al.  Multiple sclerosis treatment and infectious issues: update 2013 , 2014, Clinical and experimental immunology.

[4]  Linda J. Scarazzini,et al.  Central nervous system herpes simplex and varicella zoster virus infections in natalizumab-treated patients. , 2013, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[5]  Craig S. Miller,et al.  JC virus antibody status underestimates infection rates , 2013, Annals of neurology.

[6]  Yasuyuki Kihara,et al.  Fingolimod: Direct CNS effects of sphingosine 1-phosphate (S1P) receptor modulation and implications in multiple sclerosis therapy , 2013, Journal of the Neurological Sciences.

[7]  M. Sweetser,et al.  Manufacturer's response to case reports of PML. , 2013, The New England journal of medicine.

[8]  J. Weis,et al.  PML in a patient treated with fumaric acid. , 2013, The New England journal of medicine.

[9]  F. Barkhof,et al.  PML in a patient treated with dimethyl fumarate from a compounding pharmacy. , 2013, The New England journal of medicine.

[10]  J. A. Charles Disease-modifying drugs for multiple sclerosis in pregnancy: A systematic review , 2013, Neurology.

[11]  Jeffrey A. Cohen,et al.  Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial , 2012, The Lancet.

[12]  Christian Confavreux,et al.  Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial , 2012, The Lancet.

[13]  D. Arnold,et al.  Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. , 2012, The New England journal of medicine.

[14]  David H. Miller,et al.  Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. , 2012, The New England journal of medicine.

[15]  Tamara Castillo-Triviño,et al.  Hepatitis autoinmune en un paciente con esclerosis múltiple en tratamiento con acetato de glatiramero , 2012 .

[16]  T. Vollmer,et al.  Update on PML and PML-IRIS Occurring in Multiple Sclerosis Patients Treated With Natalizumab , 2012, Journal of neuropathology and experimental neurology.

[17]  F. Paul,et al.  Mitoxantrone Induces Natural Killer Cell Maturation in Patients with Secondary Progressive Multiple Sclerosis , 2012, PloS one.

[18]  L. Kappos,et al.  Teriflunomide added to interferon-β in relapsing multiple sclerosis , 2012, Neurology.

[19]  Meena Subramanyam,et al.  Risk of natalizumab-associated progressive multifocal leukoencephalopathy. , 2012, The New England journal of medicine.

[20]  K. Subramaniam,et al.  Glatiramer acetate induced hepatotoxicity. , 2012, Current drug safety.

[21]  A. Bar-Or,et al.  Long-term follow-up of a phase 2 study of oral teriflunomide in relapsing multiple sclerosis: safety and efficacy results up to 8.5 years , 2012, Multiple sclerosis.

[22]  R. Rhoades,et al.  New treatments and treatment goals for patients with relapsing-remitting multiple sclerosis. , 2012, Current opinion in neurology.

[23]  H. Hartung,et al.  Vaccination against infection in patients with multiple sclerosis , 2012, Nature Reviews Neurology.

[24]  T. Korn,et al.  Immune mechanisms of new therapeutic strategies in MS: teriflunomide. , 2012, Clinical immunology.

[25]  A. López de Munain,et al.  [Autoimmune hepatitis in a patient with multiple sclerosis under treatment with glatiramer acetate]. , 2012, Revista de neurologia.

[26]  Christian Confavreux,et al.  Randomized trial of oral teriflunomide for relapsing multiple sclerosis. , 2011, The New England journal of medicine.

[27]  Y. Ben-Shlomo,et al.  Autoimmune disease after alemtuzumab treatment for multiple sclerosis in a multicenter cohort , 2011, Neurology.

[28]  Ludwig Kappos,et al.  Natalizumab treatment for multiple sclerosis: updated recommendations for patient selection and monitoring , 2007, The Lancet Neurology.

[29]  D. Herr,et al.  FTY720 (fingolimod) efficacy in an animal model of multiple sclerosis requires astrocyte sphingosine 1-phosphate receptor 1 (S1P1) modulation , 2010, Proceedings of the National Academy of Sciences.

[30]  K. Simon,et al.  Anti‐JC virus antibodies: Implications for PML Risk Stratification , 2010, Annals of neurology.

[31]  H. Neumann,et al.  Functional role of brain-derived neurotrophic factor in neuroprotective autoimmunity: therapeutic implications in a model of multiple sclerosis. , 2010, Brain : a journal of neurology.

[32]  Bernhard Hemmer,et al.  Recommendations for clinical use of data on neutralising antibodies to interferon-beta therapy in multiple sclerosis , 2010, The Lancet Neurology.

[33]  J. Geddes,et al.  Cardiotoxicity and other adverse events associated with mitoxantrone treatment for MS , 2010, Neurology.

[34]  Ludwig Kappos,et al.  Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. , 2010, The New England journal of medicine.

[35]  Ludwig Kappos,et al.  A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. , 2010, The New England journal of medicine.

[36]  M. Sahraian,et al.  Alemtuzumab and multiple sclerosis: therapeutic application. , 2010, Expert opinion on biological therapy.

[37]  J. Wolinsky,et al.  Continuous long-term immunomodulatory therapy in relapsing multiple sclerosis: results from the 15-year analysis of the US prospective open-label study of glatiramer acetate , 2010, Multiple sclerosis.

[38]  S. Dhib-jalbut,et al.  Interferon-β mechanisms of action in multiple sclerosis , 2010, Neurology.

[39]  D. Solís US Food and Drug Administration , 2010 .

[40]  E. Major,et al.  Monoclonal antibodies and progressive multifocal leukoencephalopathy , 2009, mAbs.

[41]  M. Filippi,et al.  250 μg or 500 μg interferon beta-1b versus 20 mg glatiramer acetate in relapsing-remitting multiple sclerosis: a prospective, randomised, multicentre study , 2009, The Lancet Neurology.

[42]  H. Hartung,et al.  INTERFERON BETA TREATMENT DOES NOT INDUCE ORGAN-SPECIFIC AUTOANTIBODIES IN MULTIPLE SCLEROSIS , 2009, Neurology.

[43]  B. Sharrack,et al.  Melanoma complicating treatment with Natalizumab (Tysabri) for multiple sclerosis , 2009, Journal of Neurology.

[44]  M. Ban,et al.  IL-21 drives secondary autoimmunity in patients with multiple sclerosis, following therapeutic lymphocyte depletion with alemtuzumab (Campath-1H). , 2009, The Journal of clinical investigation.

[45]  Hans Lassmann,et al.  The relation between inflammation and neurodegeneration in multiple sclerosis brains , 2009, Brain : a journal of neurology.

[46]  K. Selmaj,et al.  Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. , 2008, The New England journal of medicine.

[47]  M. Atkins,et al.  Melanoma complicating treatment with natalizumab for multiple sclerosis. , 2008, The New England journal of medicine.

[48]  M. Krumbholz,et al.  Delayed allergic reaction to natalizumab associated with early formation of neutralizing antibodies. , 2007, Archives of neurology.

[49]  S. Youssef,et al.  Type II monocytes modulate T cell–mediated central nervous system autoimmune disease , 2007, Nature Medicine.

[50]  M. Trojano,et al.  Glatiramer acetate in multiple sclerosis: a review. , 2007, CNS drug reviews.

[51]  J. De Keyser,et al.  Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes , 2006, Neurology.

[52]  Urso FORTE. Urso HIGHLIGHTS OF PRESCRIBING INFORMATION , 2007 .

[53]  H P Hartung,et al.  Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes , 2006, Neurology.

[54]  R. Scheyer,et al.  A Phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses , 2006, Neurology.

[55]  Christian Confavreux,et al.  Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. , 2006, The New England journal of medicine.

[56]  Ludwig Kappos,et al.  A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. , 2006, The New England journal of medicine.

[57]  L. Durelli,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 , 2006, Multiple sclerosis.

[58]  H. Hartung,et al.  Therapeutic role of mitoxantrone in multiple sclerosis. , 2006, Pharmacology & therapeutics.

[59]  M. Sela,et al.  The immunomodulator glatiramer acetate augments the expression of neurotrophic factors in brains of experimental autoimmune encephalomyelitis mice. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[60]  D. Goodin,et al.  Benefits of high-dose, high-frequency interferon beta-1a in relapsing–remitting multiple sclerosis are sustained to 16 months: Final comparative results of the EVIDENCE trial , 2005, Journal of the Neurological Sciences.

[61]  K. Tyler,et al.  Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis. , 2005, The New England journal of medicine.

[62]  S. Atlas,et al.  Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. , 2005, The New England journal of medicine.

[63]  L. Murri,et al.  Long-term follow-up of 106 multiple sclerosis patients undergoing interferon-beta 1a or 1b therapy: predictive factors of thyroid disease development and duration. , 2005, The Journal of clinical endocrinology and metabolism.

[64]  H. Hartung,et al.  Immune response to immunotherapy: the role of neutralising antibodies to interferon beta in the treatment of multiple sclerosis , 2005, The Lancet Neurology.

[65]  M. Rovaris,et al.  Glatiramer acetate in multiple sclerosis , 2005, Expert review of neurotherapeutics.

[66]  C. Sindic,et al.  Severe delayed heart failure in three multiple sclerosis patients previously treated with mitoxantrone , 2005, Journal of Neurology.

[67]  H. Tremlett Randomized multicenter trial of natalizumab in acute MS relapses: Clinical and MRI effects , 2005, Neurology.

[68]  C. Farina,et al.  Multiple sclerosis: glatiramer acetate inhibits monocyte reactivity in vitro and in vivo. , 2004, Brain : a journal of neurology.

[69]  C. Weiller,et al.  Severe heart failure in a young multiple sclerosis patient , 2003, Journal of Neurology.

[70]  H. Hartung,et al.  Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial , 2002, The Lancet.

[71]  D. Goodkin,et al.  A study of therapy-related acute leukaemia after mitoxantrone therapy for multiple sclerosis , 2002, Multiple sclerosis.

[72]  Michael D. Davis,et al.  The Immune Modulator FTY720 Targets Sphingosine 1-Phosphate Receptors* , 2002, The Journal of Biological Chemistry.

[73]  A. Ghezzi,et al.  Thyroid function and autoimmunity during interferon β-1b treatment : A multicenter prospective study , 2001 .

[74]  Richard A. C. Hughes,et al.  PRISMS-4: Long-term efficacy of interferon-&bgr;-1a in relapsing MS , 2001, Neurology.

[75]  J. R. Scotti,et al.  Available From , 1973 .

[76]  J H Simon,et al.  Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. , 2000, The New England journal of medicine.

[77]  P. Altmeyer,et al.  Treatment of severe psoriasis with fumaric acid esters: scientific background and guidelines for therapeutic use , 1999, The British journal of dermatology.

[78]  A. Compston,et al.  Monoclonal antibody treatment exposes three mechanisms underlying the clinical course of multiple sclerosis , 1999, Annals of neurology.

[79]  H. Lassmann,et al.  Lethal capillary leak syndrome after a single administration of interferon beta-1b. , 1999, Neurology.

[80]  G. Ebers,et al.  Randomised double-blind placebo-controlled study of interferon β-1a in relapsing/remitting multiple sclerosis , 1998, The Lancet.

[81]  J S Wolinsky,et al.  Extended use of glatiramer acetate (Copaxone) is well tolerated and maintains its clinical effect on multiple sclerosis relapse rate and degree of disability , 1998, Neurology.

[82]  B. Weinshenker,et al.  The Natural History of Multiple Sclerosis: Update 1998 , 1998, Seminars in neurology.

[83]  E. Cabanis,et al.  Therapeutic effect of mitoxantrone combined with methylprednisolone in multiple sclerosis: a randomised multicentre study of active disease using MRI and clinical criteria. , 1997, Journal of neurology, neurosurgery, and psychiatry.

[84]  S. Reingold,et al.  Defining the clinical course of multiple sclerosis , 1996, Neurology.

[85]  C. Granger,et al.  Intramuscular interferon beta‐1a for disease progression in relapsing multiple sclerosis , 1996, Annals of neurology.

[86]  J. W. Rose,et al.  Copolymer 1 reduces relapse rate and improves disability in relapsing‐remitting multiple sclerosis , 1995, Neurology.

[87]  Jeffrey A. Cohen,et al.  Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group. , 1995, Neurology.

[88]  J. Tite,et al.  Humanized monoclonal antibody CAMPATH‐1H: myeloma cell expression of genomic constructs, nucleotide sequence of cDNA constructs and comparison of effector mechanisms of myeloma and Chinese hamster ovary cell‐derived material , 1992, Clinical and experimental immunology.

[89]  G. Hale,et al.  Removal of T cells from bone marrow for transplantation: a monoclonal antilymphocyte antibody that fixes human complement. , 1983, Blood.

[90]  A. Meshorer,et al.  Suppression of experimental allergic encephalomyelitis by a synthetic polypeptide , 1971, European journal of immunology.

[91]  W SCHWECKENDIEK,et al.  [Treatment of psoriasis vulgaris]. , 1959, Medizinische Monatsschrift.