Early stage and long term treatment of multiple sclerosis with interferon-beta.
Multiple sclerosis (MS) affects young adults during the most productive years of their lives, and until recently many neurologists were limited to treating symptoms and attacks without any ability to alter the disease course. The 1990s ushered in an era of possibility with the approval of three interferon-beta (IFNbeta) therapies for the treatment of MS. Though the mechanism of action of these agents is not completely understood, it is clear they reduce magnetic resonance imaging (MRI) activity as well as improve clinical outcomes. The principal randomized, blinded, multicenter trials of IFNbeta all point to the need for early treatment soon after the diagnosis of MS is made. Efficacy has also been shown in patients treated after a first demyelinating event. Data on IFNbeta in the treatment of secondary progressive MS (SPMS) is not impressive, although it shows some benefit in SPMS patients who continue to experience MRI activity and clinical relapses, signifying a continued inflammatory component to their disease. There has been no proven efficacy of IFNbeta in the treatment of primary progressive MS (PPMS). The IFNbeta therapies are generally well tolerated with a favorable side effect profile. Despite benefits in MRI and clinical measures such as relapse rates and Expanded Disability Status Scale progression, patients continue to exhibit clinical progression and radiological atrophy, pointing to confounding factors and perhaps multiple etiologies of a disease that is not yet fully understood. In addition, the subject of neutralizing antibodies has recently assumed importance. The significance of these on treatment efficacy is uncertain, and until a universally accepted reliable assay is adopted, the decision to change treatment continues to rely on the clinical interpretation of the patient's history and physical examination. Additional recommendations for management of patients, informed by the best available evidence, are also presented.
Applebee
Angela
A
Department of Neurology, University of Vermont College of Medicine, and Neurology Service, Fletcher Allen Health Care, Burlington, VT, USA.
Panitch
Hillel
H
Lancet. 1998 Nov 7;352(9139):1491-7
9820296
Ann Neurol. 1997 May;41(5):669-74
9153530
Neurology. 2002 Nov 12;59(9):1412-20
12427893
Neurology. 2001 May 22;56(10):1416
11376205
J Interferon Res. 1993 Oct;13(5):333-40
8301153
Neurology. 2007 Mar 27;68(13):977-84
17389300
Neurology. 2002 Sep 24;59(6):802-8
12349849
Mult Scler. 2007 May;13(4):459-70
17463069
Ann Neurol. 2001 May;49(5):677-81
11357961
Neurobiol Dis. 1999 Jun;6(3):149-66
10408805
Ann Neurol. 1983 Mar;13(3):227-31
6847134
Drug Saf. 2003;26(11):815-27
12908850
Neurology. 1996 Jan;46(1):12-8
8559358
Neurology. 1999 Apr 12;52(6):1277-9
10214759
Neurology. 2002 Apr 23;58(8 Suppl 4):S3-9
11971121
Nat Immunol. 2001 Sep;2(9):785-8
11526386
Neurology. 2002 Jan 22;58(2):169-78
11805241
Neurology. 2004 Feb 24;62(4):628-31
14981183
Neurology. 2006 Apr 11;66(7):1056-60
16510769
Lancet. 2001 May 19;357(9268):1576-82
11377645
Lancet. 2004 Oct 23-29;364(9444):1489-96
15500893
Neurology. 2006 Oct 10;67(7):1242-9
16914693
J Neuroimmunol. 2005 Apr;161(1-2):169-76
15748956
Neurology. 1999 Nov 10;53(8):1622-7
10563602
Neurology. 2004 Nov 23;63(10):1788-95
15557491
Neurology. 1996 Apr;46(4):907-11
8780061
Mult Scler. 2009 Feb;15(2):219-28
18755819
Neurology. 2002 Nov 26;59(10):1507-17
12451189
Mult Scler. 2007 Nov;13(9):1138-45
17967841
J Interferon Cytokine Res. 2008 May;28(5):317-31
18547162
Neurology. 2001 Jun 12;56(11):1496-504
11402106
Neurology. 2001 Jun 26;56(12):1628-36
11425926
Neurology. 1983 Nov;33(11):1444-52
6685237
Mult Scler. 1999 Aug;5(4):244-50
10467383
J Neuroimmunol. 2008 Mar;195(1-2):116-20
18279974
Ann Neurol. 2001 Jul;50(1):121-7
11456302
Ann Neurol. 1996 Dec;40(6):853-63
9007090
J Neuroimmunol. 2001 Nov 1;120(1-2):199-207
11694335
Clin Ther. 1997 Sep-Oct;19(5):883-93
9385477
Neurology. 2002 Sep 10;59(5):679-87
12221157
Neurology. 1999 Jun 10;52(9):1893-5
10371541
Neurology. 2002 Nov 26;59(10):1496-506
12451188
Mult Scler. 2007 Nov;13(9):1153-60
17967843
Neurology. 2005 Sep 27;65(6):807-11
16186517
Ann Neurol. 1999 Aug;46(2):197-206
10443885
Brain. 2003 Jun;126(Pt 6):1419-29
12764062
Arch Neurol. 2001 Aug;58(8):1297-8
11493173
Mult Scler. 1996 Apr;1(5):262-9
9345428
Lancet. 2007 Aug 4;370(9585):389-97
17679016
Neurology. 1995 Jul;45(7):1277-85
7617182
Neurology. 1998 Dec;51(6):1698-702
9855525
Neurology. 2001 Jun 12;56(11):1505-13
11402107
Arch Neurol. 2005 May;62(5):785-92
15883267
Ann Neurol. 1996 Mar;39(3):285-94
8602746
J Neurol. 2004 Mar;251(3):305-9
15015010
J Neuroimmunol. 2007 Apr;185(1-2):168-74
17328965
Neurology. 1999 Sep 11;53(4):679-86
10489026
Mult Scler. 2004 Apr;10(2):139-44
15124757
Neurology. 1993 Apr;43(4):662-7
8469319
Neurology. 1998 Sep;51(3):682-9
9748010
Arch Neurol. 2005 Apr;62(4):563-8
15824253
Ann Neurol. 2004 Aug;56(2):192-205
15293271
J Neurol Sci. 2005 Dec 15;239(1):67-74
16169561
Ann Neurol. 2000 Dec;48(6):885-92
11117545
Neurology. 2006 Sep 26;67(6):944-53
17000959
Lancet. 2002 Apr 27;359(9316):1453-60
11988242
J Neuroimmunol. 1993 Jul;46(1-2):145-53
8360326
Brain. 2008 Mar;131(Pt 3):808-17
18234696
J Neurol Sci. 2007 Jan 31;252(2):121-9
17188301
Lancet. 1998 Nov 7;352(9139):1498-504
9820297
Neurology. 2004 Nov 23;63(10):1779-87
15557490
Neurology. 2003 Jan 14;60(1):44-51
12525716
N Engl J Med. 2000 Sep 28;343(13):898-904
11006365
Ann Neurol. 1995 May;37(5):611-9
7755356
J Neuroimmunol. 1999 Dec;100(1-2):252-9
10695735
Neurology. 1997 Aug;49(2):358-63
9270562
Ann Neurol. 1996 Dec;40(6):846-52
9007089