Escalating immunotherapy of multiple sclerosis--new aspects and practical application.
Recent clinical studies in multiple sclerosis (MS) provide new data on the treatment of clinically isolated syndromes, on secondary progression, on direct comparison of immunomodulatory treatments and on dosing issues. All these studies have important implications for the optimized care of MS patients. The multiple sclerosis therapy consensus group (MSTCG) critically evaluated the available data and provides recommendations for the application of immunoprophylactic therapies. Initiation of treatment after the first relapse may be indicated if there is clear evidence on MRI for subclinical dissemination of disease. Recent trials show that the efficacy of interferon beta treatment is more likely if patients in the secondary progressive phase of the disease still have superimposed bouts or other indicators of inflammatory disease activity than without having them. There are now data available, which suggest a possible dose-effect relation for recombinant beta-interferons. These studies have to be interpreted with caution, as some potentially important issues in the design of these studies (e. g. maintenance of blinding in the clinical part of the study) were not adequately addressed. A meta-analysis of selected interferon trials has been published challenging the value of recombinant IFN beta in MS. The pitfalls of that report are discussed in the present review as are other issues relevant to treatment including the new definition of MS, the problem of treatment failure and the impact of cost-effectiveness analyses. The MSTCG panel recommends that the new diagnostic criteria proposed by McDonald et al. should be applied if immunoprophylactic treatment is being considered. The use of standardized clinical documentation is now generally proposed to facilitate the systematic evaluation of individual patients over time and to allow retrospective evaluations in different patient cohorts. This in turn may help in formulating recommendations for the application of innovative products to patients and to health care providers. Moreover, in long-term treated patients, secondary treatment failure should be identified by pre-planned follow-up examinations, and other treatment options should then be considered.
Rieckmann
P
P
Dept. of Neurology, Josef-Schneider-Str. 11, 97080, Würzburg, Germany. p.rieckmann@mail.uni-wuerzburg.de
Toyka
K V
KV
Bassetti
C
C
Beer
K
K
Beer
S
S
Buettner
U
U
Chofflon
M
M
Götschi-Fuchs
M
M
Hess
K
K
Kappos
L
L
Kesselring
J
J
Goebels
N
N
Ludin
H-P
HP
Mattle
H
H
Schluep
M
M
Vaney
C
C
Baumhackl
U
U
Berger
T
T
Deisenhammer
F
F
Fazekas
F
F
Freimüller
M
M
Kollegger
H
H
Kristoferitsch
W
W
Lassmann
H
H
Markut
H
H
Strasser-Fuchs
S
S
Vass
K
K
Altenkirch
H
H
Bamborschke
S
S
Baum
K
K
Benecke
R
R
Brück
W
W
Dommasch
D
D
Elias
W G
WG
Gass
A
A
Gehlen
W
W
Haas
J
J
Haferkamp
G
G
Hanefeld
F
F
Hartung
H-P
HP
Heesen
C
C
Heidenreich
F
F
Heitmann
R
R
Hemmer
B
B
Hense
T
T
Hohlfeld
R
R
Janzen
R W C
RW
Japp
G
G
Jung
S
S
Jügelt
E
E
Koehler
J
J
Kölmel
W
W
König
N
N
Lowitzsch
K
K
Manegold
U
U
Melms
A
A
Mertin
J
J
Oschmann
P
P
Petereit
H-F
HF
Pette
M
M
Pöhlau
D
D
Pohl
D
D
Poser
S
S
Sailer
M
M
Schmidt
S
S
Schock
G
G
Schulz
M
M
Schwarz
S
S
Seidel
D
D
Sommer
N
N
Stangel
M
M
Stark
E
E
Steinbrecher
A
A
Tumani
H
H
Voltz
R
R
Weber
F
F
Weinrich
W
W
Weissert
R
R
Wiendl
H
H
Wiethölter
H
H
Wildemann
U
U
Zettl
U K
UK
Zipp
F
F
Zschenderlein
R
R
Izquierdo
G
G
Kirjazovas
A
A
Packauskas
L
L
Miller
D
D
Koncan Vracko
B
B
Millers
A
A
Orologas
A
A
Panellus
M
M
Sindic
C J M
CJ
Bratic
M
M
Svraka
A
A
Vella
N R
NR
Stelmasiak
Z
Z
Selmaj
K
K
Bartosik-Psujik
H
H
Mitosek-Szewczyk
K
K
Belniak
E
E
Mochecka
A
A
Bayas
A
A
Chan
A
A
Flachenecker
P
P
Gold
R
R
Kallmann
B
B
Leussink
V
V
Mäurer
M
M
Ruprecht
K
K
Stoll
G
G
Weilbach
F X
FX
D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods*; D016899:Interferon-beta / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000628:therapy*; D020528:Multiple Sclerosis, Chronic Progressive / Q000628:therapy; D016896:Treatment Outcome
D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D016899:Interferon-beta