Combination therapy in multiple sclerosis

Journal of Neuroimmunology

Volumn 231, Issue 1-2, 2011, Pages 23-31

  Milo, Ron ^a   Panitch, Hillel ^b  

^a BARZILAI MEDICAL CENTER   (Israel)

^b UNIVERSITY OF VERMONT COLLEGE OF MEDICINE   (United States)

Author keywords

Antagonistic; Clinical trials; Combination therapy; Immunomodulators; Multiple sclerosis; Synergistic

Indexed keywords

6 NITRO 7 SULFAMOYLBENZO[F]QUINOXALINE 2,3 DIONE; ALPHA INTERFERON; ATORVASTATIN; AZATHIOPRINE; BETA INTERFERON; BETA1A INTERFERON; CORTICOSTEROID; DOXYCYCLINE; FINGOLIMOD; GLATIRAMER; GLYCYLPROLYLGLUTAMIC ACID; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IMMUNOMODULATING AGENT; INOSINE; INTERFERON BETA SERINE; METHOTREXATE; MEVINOLIN; MINOCYCLINE; MITOXANTRONE; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; NATALIZUMAB; NEUROPROTECTIVE AGENT; PENTOXIFYLLINE; PLACEBO; RAPAMYCIN; ROLIPRAM; SALBUTAMOL; SIMVASTATIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; VITAMIN D;

ADD ON THERAPY; ALLERGIC ENCEPHALOMYELITIS; CARDIOVASCULAR DISEASE; DISEASE ACTIVITY; DISEASE COURSE; DISEASE SEVERITY; DRUG ANTAGONISM; DRUG DOSE COMPARISON; DRUG EFFECT; DRUG EFFICACY; DRUG HYPERSENSITIVITY; DRUG MECHANISM; DRUG MEGADOSE; DRUG POTENTIATION; DRUG SAFETY; DRUG TOLERABILITY; EVIDENCE BASED MEDICINE; FLU LIKE SYNDROME; HERPES SIMPLEX; HUMAN; HYPERGLYCEMIA; IMMUNOMODULATION; IMMUNOPATHOGENESIS; IN VITRO STUDY; LEUKOPENIA; LIVER FUNCTION TEST; LIVER TOXICITY; LOW DRUG DOSE; MONOTHERAPY; MULTIPLE SCLEROSIS; NEUROPROTECTION; NONHUMAN; PRIORITY JOURNAL; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; RELAPSE; RESPIRATORY TRACT DISEASE; RETINA MACULA EDEMA; REVIEW; SIDE EFFECT;

ANIMALS; ANTI-INFLAMMATORY AGENTS; CLINICAL TRIALS AS TOPIC; DRUG THERAPY, COMBINATION; HUMANS; IMMUNOSUPPRESSIVE AGENTS; MULTIPLE SCLEROSIS;

EID: 79952455325     PISSN: 01655728     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jneuroim.2010.10.021     Document Type: Review

References (107)

1. Bar-Or A., Vollmer T., Antel J., Arnold D.L., Bodner C.A., Campagnolo D., Gianettoni J., Jalili F., Kachuck N., Lapierre Y., Niino M., Oger J., Price M., Rhodes S., Robinson W.H., Shi F.D., Utz P.J., Valone F., Weiner L., Steinman L., Garren H. Induction of antigen-specific tolerance in multiple sclerosis after immunization with DNA encoding myelin basic protein in a randomized, placebo-controlled phase 1/2 trial. Arch. Neurol. 2007, 64:1407-1415.
2. Bastan B., Cikrikci I., Kurne A., Karlioguz K., Karabudak R. Mitoxantrone therapy in secondary progressive multiple sclerosis combination with glatiramer acetate: preliminary results. Mult. Scler. 2004, 10(Suppl 2):S269.
3. Benson K., Hartz A.J. A comparison of observational studies and randomized, controlled trials. N Engl J. Med. 2000, 342:1878-1886.
4. Birnbaum G., Cree B., Altafullah I., Zinser M., Reder A.T. Combining beta interferon and atorvastatin may increase disease activity in multiple sclerosis. Neurology 2008, 71:1390-1395.
5. Branisteanu D.D., Mathieu C., Bouillon R. Synergism between sirolimus and 1, 25-dihydroxyvitamin D3 in vitro and in vivo. J. Neuroimmunol. 1997, 79:138-147.
6. Brod S.A., Lindsey J.W., Wolinsky J.S. Combination therapy with glatiramer acetate (copolymer-1) and a type I interferon (IFN-α) does not improve experimental autoimmune encephalomyelitis. Ann. Neurol. 2000, 47:127-131.
7. Calabresi P.A., Wilterdink J.L., Rogg J.M., Mills P., Webb A., Whartenby K.A. An open-label trial of combination therapy with interferon beta-1a and oral methotrexate in MS. Neurology 2002, 58:314-317.
8. Cantonal Hospital of St.Gallen The neuroprotective effect of lamotrigine and interferon beta 1a in patients with relapsing-remitting multiple sclerosis. NCT00917839 http://www.clinicaltrials.gov/ct2/show/NCT00917839.
9. Cohen J.A., Calabresi P.A., Chakraborty S., Edwards K.R., Eickenhorst T., Felton W.L., Fisher E., Fox R.J., Goodman A.D., Hara-Cleaver C., Hutton G.J., Imrey P.B., Ivancic D.M., Mandell B.F., Perryman J.E., Scott T.F., Skaramagas T.T., Zhang H. Avonex Combination Trial in relapsing-remitting MS: rationale, design and baseline data. Mult. Scler. 2008, 14:370-382. ACT Investigators.
10. Cohen J.A., Imrey P.B., Calabresi P.A., Edwards K.R., Eickenhorst T., Felton W.L., Fisher E., Fox R.J., Goodman A.D., Hara-Cleaver C., Hutton G.J., Mandell B.F., Scott T.F., Zhang H., Apperson-Hansen C., Beck G.J., Houghtaling P.L., Karafa M.T., Stadtler M. Results of the Avonex Combination Trial (ACT) in relapsing-remitting MS. Neurology 2009, 72:535-541. ACT Investigators.
11. Cohen J.A., Barkhof F., Comi G., Hartung H.P., Khatri B.O., Montalban X., Pelletier J., Capra R., Gallo P., Izquierdo G., Tiel-Wilck K., de Vera A., Jin J., Stites T., Wu S., Aradhye S., Kappos L. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J. Med. 2010, 362:402-415. TRANSFORMS Study Group.
12. De Stefano N., Filippi M., Hawkins C. Short-term combination of glatiramer acetate with i.v. steroid treatment preceding treatment with GA alone assessed by MRI-disease activity in patients with relapsing-remitting multiple sclerosis. J. Neurol. Sci. 2008, 266:44-50. 9011 study group.
13. Dhawan N., Reder A. Statins block interferon signaling in human immune cells: potential loss of the therapeutic effect of IFN-beta in multiple sclerosis. Neurology 2007, 68:A364.
14. Dhib-Jalbut S., Marks S. Interferon-beta mechanisms of action in multiple sclerosis. Neurology 2010, 74(Suppl 1):S17-S24.
15. Dubois B., D'Hooghe M.B., De Lepeleire K., Ketelaer P., Opdenakker G., Carton H. Toxicity in a double-blind, placebo-controlled pilot trial with d-penicillamine and metacycline in secondary progressive multiple sclerosis. Mult. Scler. 1998, 4:74-78.
16. Edan G., Miller D., Clanet M. Therapeutic effect of mitoxantrone combined with methylprednisolone in multiple sclerosis: a randomised multicentre study of active disease using MRI and clinical criteria. J. Neurol. Neurosurg. Psychiatry 1997, 62:112-118.
17. Farina C., Weber M.S., Meinl E., Wekerle H., Hohlfeld R. Glatiramer acetate in multiple sclerosis: update on potential mechanisms of action. Lancet Neurol. 2005, 4:567-575.
18. Fernández O. Risk-benefit assessment of combination therapy of interferon-beta-1a at high dose and mitoxantrone in worsening relapsing-remitting and secondary progressive multiple sclerosis. Mult. Scler. 2004, 10(Suppl 2):S268-S269. the Iberian Collaborative Group.
19. Fernández O., Guerrero M., Mayorga C., Muñoz L., Leán A., Luque G., Hervás M., Fernández V., Capdevila A., de Ramón E. Combination therapy with interferon beta-1b and azathioprine in secondary progressive multiple sclerosis. A two-year pilot study. J. Neurol. 2002, 249:1058-1062.
20. Freedman M., Wolinsky J.S., Byrnes W.J., Confavreux C., Comi G., Frangin G., Kappos L., Olsson T., Miller A., O'Connor P.W. Oral teriflunomide or placebo added to interferon beta for 6months in patients with relapsing multiple sclerosis: safety and efficacy results. Mult. Scler. 2009, 15(Suppl 2):S273.
21. Freedman M., Wolinsky J.S., Frangin G.A., Confavreux C., Comi G., Byrnes W.J., Kappos L., Olsson T., Miller A., O'Connor P. Oral teriflunomide or placebo added to glatiramer acetate for 6months in patients with relapsing multiple sclerosis: safety and efficacy results. Neurology 2010, 74(Suppl 2):A293.
22. Friedemann P., Aktas O., Vaiczies S., Wurfel J., Bellmann-Strobl J., Dorr J.M., Vaiczies H., Hortle, Wernecke M.D., Volk H.D., Zipp F. High dose atorvastatin alone or in combination with interferon-beta (IFN-beta) in the treatment of relapsing remitting multiple sclerosis (RR-MS). Neurology 2008, 70(Suppl 1):A86.
23. Frohman E., Cutter G., Remington J., Gao H., Rossman H., Weinstock-Guttman B., Durfee J.E., Conger A., Carl E., Treadaway K., Lindzen E., Salter A., Frohman T.C., Shah A., Bates A., Cox J.L., Dwyer M.G., Stuve O., Greenberg B.M., Racke M.K., Zivadinov R. A randomized, blinded, parallel-group, pilot trial of mycophenolate mofetil (CellCept) compared with interferon beta-1a (Avonex) in patients with relapsing remitting multiple sclerosis. Ther. Adv. Neurol. Disord. 2010, 3:15-28.
24. Gasperini C., Pozzilli C., Bastianello S., Koudriavtseva T., Galgani S., Millefiorini E., Paolillo A., Horsfield M.A., Bozzao L., Fieschi C. Effect of steroids on Gd-enhancing lesions before and during recombinant beta interferon 1a treatment in relapsing remitting multiple sclerosis. Neurology 1998, 50:403-406.
25. Gharagozli K., Fallahi F., Meraj Mohammadi M., Moslemi Zadeh M., Abdoli N., Abadian S. Safety and efficacy of combination therapy with interferon-beta-1a and methotrexate in worsening multiple sclerosis. Mult. Scler. 2004, 10(Suppl 2):S263.
26. Giuliani F., Metz L.M., Wilson T., Fan Y., Bar-Or A., Yong V.W. Additive effect of the combination of glatiramer acetate and minocycline in a model of MS. J. Neuroimmunol. 2005, 158:213-221.
27. Giuliani F., Fu S.A., Metz L.M., Yong V.W. Effective combination of minocycline and interferon-beta in a model of multiple sclerosis. J. Neuroimmunol. 2005, 165:83-91.
28. Gogovska L., Ljapcev R. Interferon beta combined with mycophenolate mofetil in multiple sclerosis. Mult. Scler. 2005, 11(Suppl 1):S170.
29. Goodman A.D., Rossman H., Bar-Or A., Miller A., Miller D.H., Schmierer K., Lublin F., Khan O., Bormann N.M., Yang M., Panzara M.A., Sandrock A.W. GLANCE: results of a phase 2, randomized, double-blind, placebo-controlled study. Neurology 2009, 72:806-812. GLANCE Investigators.
30. Hartung H.P., Gonsette R., Konig N., Kwiecinski H., Guseo A., Morrissey S.P., Krapf H., Zwingers T. Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial. Lancet 2002, 360:2018-2025. Mitoxantrone in Multiple Sclerosis Study Group (MIMS).
31. Havrdova E., Zivadinov R., Krasensky J., Dwyer M.G., Novakova I., Dolezal O., Ticha V., Dusek L., Houzvickova E., Cox J.L., Bergsland N., Hussein S., Svobodnik A., Seidl Z., Vaneckova M., Horakova D. Randomized study of interferon beta-1a, low-dose azathioprine, and low-dose corticosteroids in multiple sclerosis. Mult. Scler. 2009, 15:965-976.
32. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis: I. Clinical results of a multicenter, randomized, double-blind, placebo controlled trial. Neurology 1993, 43:655-661. IFNB Multiple Sclerosis Study Group.
33. Jacobs L.D., Cookfair D.L., Rudick R.A., et al. Intramuscular interferon beta-1a for disease progression in exacerbating-remitting multiple sclerosis. Ann. Neurol. 1996, 39:285-294.
34. Jeffery D.R., Chepuri N., Durden D., Burdette J. A pilot trial of combination therapy with mitoxantrone and interferon beta-1b using monthly gadolinium-enhanced magnetic resonance imaging. Mult. Scler. 2005, 11:296-301.
35. Johnson K.P., Brooks B.R., Cohen J.A., Ford C.C., Goldstein J., Lisak R.P., Myers L.W., Panitch H.S., Rose J.W., Schiffer R.B. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase Ill multi-center, double-blind, placebo-controlled trial. Neurology 1995, 45:1268-1276.
36. Kalanie H., Tabatabai S.S. Combined immunoglobulin and azathioprine in multiple sclerosis. Eur. Neurol. 1998, 39:178-181.
37. Kalman B., Lublin F.D. Spectrum and classification of inflammatory demyelinating diseases of the central nervous system. Curr. Neurol. Neurosci. Rep. 2001, 1:249-256.
38. Kamm C.P., Mattle H.P. SWiss Atorvastatin and interferon Beta-1b trial In Multiple Sclerosis (SWABIMS) - rationale, design and methodology. Trials 2009, 10:115. SWABIMS Study Group.
39. Kanwar J.R., Kanwar R.K., Krissansen G.W. Simultaneous neuroprotection and blockade of inflammation reverses autoimmune encephalomyelitis. Brain 2004, 127:1313-1331.
40. Kappos L., Radue E.W., O'Connor P., Polman C., Hohlfeld R., Calabresi P., Selmaj K., Agoropoulou C., Leyk M., Zhang-Auberson L., Burtin P. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J. Med. 2010, 362:387-401. FREEDOMS Study Group.
41. Kieseier B.C., Archelos J.J., Hartung H.P. Different effects of simvastatin and interferon beta on the proteolytic activity of matrix metalloproteinases. Arch. Neurol. 2004, 61:929-932.
42. Khoury S.J., Healy B.C., Kivisäkk P., Viglietta V., Egorova S., Guttmann C.R., Wedgwood J.F., Hafler D.A., Weiner H.L., Buckle G., Cook S., Reddy S. A randomized controlled double-masked trial of albuterol add-on therapy in patients with multiple sclerosis. Arch. Neurol. 2010, 67:1055-1061.
43. Knobler R.L., Greenstein J.I., Johnson K.P., Lublin F.D., Panitch H.S., Conway K., Grant-Gorsen S.V., Muldoon J., Marcus S.G., Wallenberg J.C., Willimas G.J., Yoshizawa C.N. Systemic recombinant human interferon-beta treatment of relapsing-remitting multiple sclerosis: pilot study analysis and six-year follow-up. J. Interferon Res. 1993, 13:333-340.
44. Lanzillo R., Orefice G., Quarantelli M., Rinaldi C., Prinster A., Ventrella G., Spitaleri D., Lus G., Vacca G., Carotenuto B., Salvatore E., Brunetti A., Tedeschi G., Brescia Morra V. 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, 16:450-454.
45. Linker R.A., Kieseier B.C. Innovative monoclonal antibody therapies in multiple sclerosis. Ther. Adv. Neurol. Disord. 2009, 1:33-42.
46. Lublin F., Baier M., Cutter G., Bever C., Elfont R., Khan O., Lisak R., McFarland H., Narayana P., Noseworthy J., Panitch H., Reingold S., Weber M., Whitaker J., Wolinsky J., Bashir K., Johnson K. Results of the extension of a trial to assess the long term safety of combining interferon beta-1a and glatiramer acetate. Neurology 2002, 58(Suppl 3):A85.
47. Lublin F., Cofield S.S., Cutter G.R., Conwit R., Narayana P., Nelson F., Wolinsky J. The CombiRx cohort at baseline with clinical and MRI differences by diagnostic criteria. Neurology 2009, 72(Suppl 3):A255.
48. Luccarini I., Ballerini C., Biagioli T., Biamonte F., Bellucci A., Rosi M.C., Grossi C., Massacesi L., Casamenti F. Combined treatment with atorvastatin and minocycline suppresses severity of EAE. Exp. Neurol. 2008, 211:214-226.
49. Lucchinetti C.F., Bruck W., Rodriguez M., Lassmann H. Distinct patterns of multiple sclerosis pathology indicates heterogeneity on pathogenesis. Brain Pathol. 1996, 6:259-274.
50. Lucchinetti C., Bruck W., Parisi J., Scheithauer B., Rodriguez M., Lassmann H. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann. Neurol. 2000, 47:707-717.
51. Lus G., Romano F., Scuotto A., Accardo C., Cotrufo R. Azathioprine and interferon beta(1a) in relapsing-remitting multiple sclerosis patients: increasing efficacy of combined treatment. Eur. Neurol. 2004, 51:15-20.
52. Markovic-Plese S., Speer D., Jin J., Chen Y., Smrtka J., Ingram L., Jewells V. Statin and intramuscular interferon beta-1a combination therapy is safe and well tolerated in patients with clinically isolated syndrome suggestive of multiple sclerosis, a pilot study. Mult. Scler. 2007, 13(Suppl 2):S270.
53. Markovic-Plese S., Singh A.K., Singh I. Therapeutic potential of statins in multiple sclerosis: immune modulation, neuroprotection and neurorepair. Future Neurol. 2008, 3:153-167.
54. Martinelli V., Comi G. Induction versus escalation therapy. Neurol. Sci. 2005, 26(Suppl 4):S193-S199.
55. Merck KGaA Minocycline as add-on to interferon Beta-1a (Rebif®) in relapsing remitting multiple sclerosis (RECYCLINE). NCT01134627 http://www.clinicaltrials.gov/ct2/show/NCT01134627.
56. Metz L.M., Li D., Traboulsee A., Myles M.L., Duquette P., Godin J., Constantin M., Yong V.W. Glatiramer acetate in combination with minocycline in patients with relapsing-remitting multiple sclerosis: results of a Canadian, multicenter, double-blind, placebo-controlled trial. Mult. Scler. 2009, 15:1183-1194. GA/minocycline study investigators.
57. Mihancea P., Brisc C.M., Havasi N., Brisc C. Combined therapy with mitoxantrone and methyl-prednisolone in multiple sclerosis. Mult. Scler. 2006, 12(Suppl 1):S79.
58. Milo R., Panitch H. Additive effects of copolymer-1 and interferon beta-1b on the immune response to myelin basic protein. J. Neuroimmunol. 1995, 61:185-193.
59. Minagar A., Alexander J.S., Schwendimann R.N., Kelley R.E., Gonzalez-Toledo E., Jimenez J.J., Mauro L., Jy W., Smith S.J. Combination therapy with interferon beta-1a and doxycycline in multiple sclerosis: an open-label trial. Arch. Neurol. 2008, 65:199-204.
60. Munoz-Garcia D., Marin M., Lopez J., Arias M., Papena D., Alonso-Alonso M., Martinez J., Vazquez F. Inosine and interferon beta 1a: preliminary results of a clinical trial in multiple sclerosis. Mult. Scler. 2004, 10(suppl 2):S272.
61. National MS Society Clinical trials in multiple sclerosis 2010: planned, in progress, recently completed http://www.nationalmssociety.org/research/clinical-trials/index.aspx.
62. Niino M. Vitamin D and its immunoregulatory role in multiple sclerosis. Drugs Today Barc. 2010, 46:279-290.
63. O'Connor P., Filippi M., Arnason B., Comi G., Cook S., Goodin D., Hartung H.P., Jeffery D., Kappos L., Boateng F., Filippov V., Groth M., Knappertz V., Kraus C., Sandbrink R., Pohl C., Bogumil T. 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, 8:889-897. BEYOND Study Group.
64. Oztekin N.S., Oztekin F.M., Munis O.B. Atorvastatin combined with interfereon beta 1a in relapsing-remitting multiple sclerosis: preliminary results of a 24month randomized open-label clinical trial. Mult. Scler. 2008, 14(Suppl 1):S171.
65. Paintlia A.S., Paintlia M.K., Singh I., Singh A.K. Combined medication of lovastatin with rolipram suppresses severity of experimental autoimmune encephalomyelitis. Exp. Neurol. 2008, 214:168-180.
66. Peterson L.K., Fujinami R.S. Inflammation, demyelination, neurodegeneration and neuroprotection in the pathogenesis of multiple sclerosis. J. Neuroimmunol. 2007, 184:37-44.
67. Polman C.H., O'Connor P.W., Havrdova E., Hutchinson M., Kappos L., Miller D.H., Phillips J.T., Lublin F.D., Giovannoni G., Wajgt A., Toal M., Lynn F., Panzara M.A., Sandrock A.W. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J. Med. 2006, 354:899-910. AFFIRM Investigators.
68. Randomised double-blind placebo-controlled study of interferon β-1a in relapsing/remitting multiple sclerosis. Lancet 1998, 352:1498-1504. PRISMS (Prevention of Relapses and Disability by Interferon β-1a Subcutaneously in Multiple Sclerosis) Study Group.
69. Pulicken M., Bash C.N., Costello K., Said A., Cuffari C., Wilterdink J.L., Rogg J.M., Mills P., Calabresi P.A. Optimization of the safety and efficacy of interferon beta 1b and azathioprine combination therapy in multiple sclerosis. Mult. Scler. 2005, 11:169-174.
70. Rammohan K.W., Shoemaker J. Emerging multiple sclerosis oral therapies. Neurology 2010, 74(Suppl 1):S47-S53.
71. Ramtahal J., Jacob A., Das K., Boggild M. Sequential maintenance treatment with glatiramer acetate after mitoxantrone is safe and can limit exposure to immunosuppression in very active, relapsing remitting multiple sclerosis. J. Neurol. 2006, 253:1160-1164.
72. Ravnborg M., Sørensen P.S., Andersson M., Celius E.G., Jongen P.J., Elovaara I., Bartholomé E., Constantinescu C.S., Beer K., Garde E., Sperling B. 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, 9:672-680.
73. Reggio E., Nicoletti A., Fiorilla T., Politi G., Reggio A., Patti F. The combination of cyclophosphamide plus interferon beta as rescue therapy could be used to treat relapsing-remitting multiple sclerosis patients - twenty-four months follow-up. J. Neurol. 2005, 252:1255-1261.
74. Remington G.M., Treadaway K., Frohman T., Salter A., Stüve O., Racke M.K., Hawker K., Agosta F., Sormani M.P., Filippi M., Frohman E.M. A one-year prospective, randomized, placebo-controlled, quadruple-blinded, phase II safety pilot trial of combination therapy with interferon beta-1a and mycophenolate mofetil in early relapsing remitting multiple sclerosis (TIME MS). Ther. Adv. Neurol. Disord. 2010, 3:3-13.
75. Richert N.D., Ostuni J.L., Bash C.N., Leist T.P., McFarland H.F., Frank J.A. Interferon beta-1b and intravenous methylprednisolone promote lesion recovery in multiple sclerosis. Mult. Scler. 2001, 7:49-58.
76. Rieckmann P. Concepts of induction and escalation therapy in multiple sclerosis. J. Neurol. Sci. 2009, 277(Suppl 1):S42-S45.
77. Rieckmann P., Weber F., Günther A., Poser S. The phosphodiesterase inhibitor pentoxifylline reduces early side effects of interferon-beta 1b treatment in patients with multiple sclerosis. Neurology 1996, 47:604.
78. Río J., Nos C., Marzo M.E., Tintoré M., Montalban X. Low-dose steroids reduce flu-like symptoms at the initiation of IFNbeta-1b in relapsing-remitting MS. Neurology 1998, 50:1910-1912.
79. Rudick R.A., Stuart W.H., Calabresi P.A., Confavreux C., Galetta S.L., Radue E.W., Lublin F.D., Weinstock-Guttman B., Wynn D.R., Lynn F., Panzara M.A., Sandrock A.W. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J. Med. 2006, 354:911-923. SENTINEL Investigators.
80. Rudick R.A., Pace A., Rani M.R., Hyde R., Panzara M., Appachi S., Shrock J., Maurer S.L., Calabresi P.A., Confavreux C., Galetta S.L., Lublin F.D., Radue E.W., Ransohoff R.M. Effect of statins on clinical and molecular responses to intramuscular interferon beta-1a. Neurology 2009, 72:1989-1993.
81. Ruggieri M., Pica C., Lia A., Zimatore G.B., Modesto M., Di Liddo E., Specchio L.M., Livre A.P., Trojano M., Avolio C. Combination treatment of glatiramer acetate and minocycline affects phenotype expression of blood monocyte-derived dendritic cells in multiple sclerosis patients. J. Neuroimmunol. 2008, 197:140-146.
82. Saida K., Zhigang Z., Ozawa K., Konishi T., Saida T. Long-term open-trial of mizoribine with prednisolone in 24 patients with multiple sclerosis: safety, clinical and magnetic resonance imaging outcome. Intern. Med. 1999, 38:636-642.
83. Sellner J., Greeve I., Leib S.L., Mattle H.P. Atorvastatin does not alter interferon Beta-induced changes of serum matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in patients with multiple sclerosis. Arch. Neurol. 2008, 65:672-674.
84. Sloka J.S., Stefanelli M. The mechanism of action of methylprednisolone in the treatment of multiple sclerosis. Mult. Scler. 2005, 11:425-432.
85. Smith D.R., Weinstock-Guttman B., Cohen J.A., Wei X., Gutmann C., Bakshi R., Olek M., Stone L., Greenberg S., Stuart D., Orav J., Stuart W., Weiner H. A randomized blinded trial of combination therapy with cyclophosphamide in patients-with active multiple sclerosis on interferon beta. Mult. Scler. 2005, 11:573-582.
86. Soos J.M., Stüve O., Youssef S., Bravo M., Johnson H.M., Weiner H.L., Zamvil S.S. Cutting edge: oral type I IFN-tau promotes a Th2 bias and enhances suppression of autoimmune encephalomyelitis by oral glatiramer acetate. J. Immunol. 2002, 169:2231-2235.
87. Sorensen P.S., Fredriksen J.L., Licke J., Sellebjerg F. Does simvastatin antagonise the effect of interferon beta? Interim safety analysis of the ongoing SIMBOMBIN study. Mult. Scler. 2007, 13(Suppl 3):S25.
88. Sorensen P.S., Mellgren S.I., Svenningsson A., Elovaara I., Frederiksen J.L., Beiske A.G., Myhr K.M., Søgaard L.V., Olsen I.C., Sandberg-Wollheim M. 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, 8:519-529.
89. Sorensen P.S., Lycke J., Erälinna J.-P., Edland A., Wu X., Frederiksen J., Oturai A., Malmeström C., Stenager E., Sperling B. No beneficial effect of simvastatin as add-on therapy to interferon-beta-1a for the treatment of relapsing-remitting multiple sclerosis: results of a large, double blind, randomized, placebo-controlled trial. Mult. Scler. 2010, 16(Suppl 10):S36-S37.
90. Stuart W.H., Court D., English J. Treatment of disease progression in relapsing multiple sclerosis with combination therapy of interferon-beta-1a (Avonex) plus pulse steroids, cyclophosphamide, and/or mycophenolate mofetil. Mult. Scler. 2004, 10(Suppl 2):S265.
91. Stüve O., Youssef S., Weber M.S., Nessler S., von Büdingen H.C., Hemmer B., Prod'homme T., Sobel R.A., Steinman L., Zamvil S.S. Immunomodulatory synergy by combination of atorvastatin and glatiramer acetate in treatment of CNS autoimmunity. J. Clin. Invest. 2006, 116:1037-1044.
92. Teva Pharmaceutical Industries Assessment study of steroid effect in relapsing multiple sclerosis subjects treated with glatiramer acetate. NCT00203047 http://www.clinicaltrials.gov/ct2/show/NCT00203047.
93. Turner N.A., O'Regan D.J., Ball S.G., Porter K.E. Simvastatin inhibits MMP-9 secretion from human saphenous vein smooth muscle cells by inhibiting the RhoA/ROCK pathway and reducing MMP-9 mRNA levels. FASEB J. 2005, 19:804-806.
94. van Etten E., Gysemans C., Branisteanu D.D., Verstuyf A., Bouillon R., Overbergh L., Mathieu C. Novel insights in the immune function of the vitamin D system: synergism with interferon-beta. J. Steroid Biochem. Mol. Biol. 2007, 103:546-551.
95. Vermersch P., Waucquier N., Michelin E., Bourteel H., Stojkovic T., Ferriby D., de Seze J. Combination of IFN beta-1a (Avonex) and mycophenolate mofetil (Cellcept) in multiple sclerosis. Eur. J. Neurol. 2007, 14:85-89.
96. Viglietta V., Greenberg S., Mikol D., Weiner J., Alteri E., Chang P., Krumwieh D., Musch B. Clinical development plan for cladribine tablets, an oral immunomodulator, for the treatment of multiple sclerosis. Mult. Scler. 2009, 15(Suppl 2):S126.
97. Visser L.H., Beekman R., Tijssen C.C., Uitdehaag B.M., Lee M.L., Movig K.L., Lenderink A.W. A randomized, double-blind, placebo-controlled pilot study of i.v. immune globulins in combination with i.v. methylprednisolone in the treatment of relapses in patients with MS. Mult. Scler. 2004, 10:89-91.
98. Vollmer T., Key L., Durkalski V., Tyor W., Corboy J., Markovic-Plese S., Preiningerova J., Rizzo M., Singh I. Oral simvastatin treatment in relapsing-remitting multiple sclerosis. Lancet 2004, 363:1607-1608.
99. Vollmer T., Panitch H., Bar-Or A., Dunn J., Freedman M.S., Gazda S.K., Campagnolo D., Deutsch F., Arnold D.L. Glatiramer acetate after induction therapy with mitoxantrone in relapsing multiple sclerosis. Mult. Scler. 2008, 14:663-670.
100. Weber F., Polak T., Günther A., Kubuschok B., Janovskaja J., Bitsch A., Poser S., Rieckmann P. Synergistic immunomodulatory effects of interferon-beta1b and the phosphodiesterase inhibitor pentoxifylline in patients with relapsing-remitting multiple sclerosis. Ann. Neurol. 1998, 44:27-34.
101. Wynn D., Kaufman M., Montalban X., Vollmer T., Simon J., Elkins J., O'Neill G., Neyer L., Sheridan J., Wang C., Fong A., Rose J.W. Daclizumab in active relapsing multiple sclerosis (CHOICE study): a phase 2, randomised, double-blind, placebo-controlled, add-on trial with interferon beta. Lancet Neurol. 2010, 9:381-390. CHOICE investigators.
102. Youssef S., Stüve O., Patarroyo J.C., Ruiz P.J., Radosevich J.L., Hur E.M., Bravo M., Mitchell D.J., Sobel R.A., Steinman L., Zamvil S.S. The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature 2002, 420:78-84.
103. Zamvil S.S., Steinman L. Diverse targets for intervention during inflammatory and neurodegenerative phases of multiple sclerosis. Neuron 2003, 38:685-688.
104. Zang Y., Hong J., Robinson R., Li S., Rivera V.M., Zhang J.Z. Immune regulatory properties and interactions of Copolymer-I and beta-interferon 1a in multiple sclerosis. J. Neuroimmunol. 2003, 137:144-153.
105. Zarkou S., Carter J.L., Wellik K.E., Demaerschalk B.M., Wingerchuk D.M. Are corticosteroids efficacious for preventing or treating neutralizing antibodies in multiple sclerosis patients treated with beta-interferons? A critically appraised topic. Neurologist 2010, 16:212-214.
106. Zivadinov R., Rudick R.A., De Masi R., Nasuelli D., Ukmar M., Pozzi-Mucelli R.S., Grop A., Cazzato G., Zorzon M. Effects of IV methylprednisolone on brain atrophy in relapsing-remitting MS. Neurology 2001, 57:1239-1247.
107. Zivadinov R., Cutter G., Rossman H., Weinstock-Guttman B., Durfee J., Cox J., Remington J., Perez S., Dwyer M.G., Racke M., Shah A., Frohman E. A randomized, open-label, parallel group, multicenter study to determine the safety and efficacy of mycophenolate mofetil (cellcept) in mono- and combination-therapy with interferon beta-1a (avonex), in patients with relapsing remitting multiple sclerosis. Neurology 2008, 70(Suppl 1):A94.