References
|
Treatment groups
|
N
|
MS type (%)
|
Mean (E)DSS baseline (SD) or
(range)
|
Randomised trial duration (years)
|
Primary efficacy outcome
|
Main efficacy results
|
British Dutch Azathioprine group
|
Azathioprine
Placebo
|
354
|
67% RRMS
9% SPMS
14% PPMS
|
AZ 3.7 (1.5)
Plc 3.7 (1.6)
|
3
|
Change in EDSS and AI
|
Neutral
|
Ellison et al.
|
Azathioprine and methylprednisolone
Azathioprine
Placebo
|
98
|
PMS
|
AZ & MP 5.4 (1.3)
AZ 5.6 (1.2)
Plc 5.5 (1.0)
|
3
|
Rate of progression in ISS, SNE and DSS
|
Neutral
|
Ghezzi et al.
|
Azathioprine
Placebo
|
185
|
40% RRMS
60% SPMS
|
SPMS only
AZ 3.8 (1–6.5)
Plc 3.7 (1–7)
|
1.5
|
DSS progression
|
Neutral
|
The MS study group
|
Cyclosporine
Placebo
|
547
|
PMS
|
CsA 5.4 (1.2)
Plc 5.4 (1.2)
|
2
|
EDSS worsening
|
Positive—high and differential dropout
|
Bornstein et al.
|
Glatiramer acetate SC
Placebo
|
106
|
PMS
|
GA 5.6
Plc 5.5
|
2
|
EDSS progression
|
Neutral
|
Canadian Co-op MS Group
|
Cyclophosphamide IV
Cyclophosphamide oral and plasma
exchange and prednisolone
Placebo
|
168
|
PMS
|
CPM 5.8 (0.6)
CPM and PLEX and Pred 5.7 (0.7)
Plc 5.8 (0.6)
|
2.5
|
Worsening in EDSS
|
Neutral
|
Beutler et al.
|
Two-period, two-treatment crossover
trial
Cladribine IV
Placebo
|
51
|
PMS
|
CL 4.8
Plc 4.6
|
2
|
Deterioration in EDSS/SNRS scores
|
Positive
|
Milanese et al.
|
Azathioprine
Placebo
|
40
|
48% RMS
52% PMS
|
AZ 3.4 (1.7)
Plc 3.1 (1.2)
|
3
|
EDSS progression
|
Neutral—high dropout rate
|
Goodkin et al.
|
Methotrexate
Placebo
|
60
|
70% SPMS
30% PPMS
|
MTX 5.5 (2.4)
Plc 5.3 (2.7)
|
2
|
EDSS, 9HPT, Box and Block Test, AI
worsening
|
Positive
|
Karussis et al.
|
Linomide
Placebo
|
30
|
SPMS
|
Lin 4.9
Plc 4.7
|
0.5
|
MRI activity
|
Positive
|
European Study Group on Interferon β-1b in secondary progressive MS
|
Interferon β-1b
SC
Placebo
|
718
|
SPMS
|
IFNβ-1b 5.1 (1.1)
Plc 5.2 (1.1)
|
3
|
3 months confirmed EDSS progression
|
Positive
|
Noseworthy et al.
|
Linomide (3 doses)
Placebo
|
715
|
13% RRMS
87% SPMS
|
Lin 5.2 (2–6.5)
Plc 5.1 (3–6.5)
|
3
|
EDSS progression
|
Terminated 1 month after fully enrolled
due to life-threatening side effects
|
Rice et al.
|
Cladribine SC (2 doses)
Placebo
|
159
|
70% SPMS
30% PPMS
|
CL 5.6
Plc 5.6
|
1
|
Mean change in EDSS
|
Neutral
|
SPECTRIMS
|
Interferon β-1a
SC (2 doses)
Placebo
|
618
|
SPMS
|
IFNβ-1a 5.4 (1.1)
Plc 5.4 (1.1)
|
3
|
3 months confirmed EDSS progression
|
Neutral
|
Skurkovich et al.
|
IFNγ Antibodies IM
TNFα Antibodies IM
Placebo
|
45
|
SPMS
|
IFNγ Ab 4.5 (3–6.5)
TNFα Ab 4.0 (3–6)
Plc 4.1 (3–7)
|
1
|
EDSS progression
|
Positive—IFNg ab only
|
Cohen et al.
|
Interferon β-1a
IM
Placebo
|
436
|
SPMS
|
IFNβ-1a 5.2 (1.1)
Plc 5.2 (1.1)
|
2
|
Baseline to month 24 change in the MSFC
|
Positive
|
Hartung et al.
|
Mitoxantrone IV (2 doses)
Placebo
|
194
|
SPMS
|
MIT 4.6 (1.0)
Plc 4.7 (1.0)
|
2
|
Change in EDSS, AI, SNS score, number
of treated relapses and time to first treated relapse
|
Positive—12 mg/m2 MIT dose only
|
Anderson et al.
|
Interferon β-1a
SC
Placebo
|
371
|
SPMS
|
IFNβ-1a 4.7
Plc 5.0
|
3
|
6 months confirmed EDSS progression
|
Neutral
|
Hommes et al.
|
Immunoglobulin IV
Placebo
|
318
|
SPMS
|
IVIG 5.3 (1.1)
Plc 5.2 (1.1)
|
2.25
|
3 months confirmed EDSS progression
|
Neutral
|
The North American Study Group on Interferon beta-1b in SPMS
|
Interferon β-1b SC (2 doses)
Placebo
|
939
|
SPMS
|
IFNβ-1b 5.2 (1.1)
Plc 5.1 (1.2)
|
3
|
6 months confirmed EDSS progression
|
Neutral
|
Warren et al.
|
MBP8298 IV
Placebo
|
32
|
69% SPMS
31% PPMS
|
MBP median 6.5 (5–7.5)
Plc median 6.3 (3.5–7)
|
2
|
EDSS progression
|
Neutral
|
Pöhlau et al.
|
Immunoglobulin IV
Placebo
|
231
|
85% SPMS
15% PPMS
|
IVIG 5.6 (1.1)
Plc 5.5 (1.2)
|
2
|
3 months confirmed EDSS progression,
improvement in function defined by best EDSS
|
Positive—high dropout rate
|
Montanari et al.
|
Azathioprine and Interferon β-1b
SC
Interferon β-1b
SC
|
85
|
SPMS
|
Not available
|
2
|
Baseline to month 24 change in the MSFC
|
Neutral—high dropout rate
|
Kapoor et al.
|
Lamotrigine
Placebo
|
120
|
SPMS
|
LTG median 6.0 (4–7)
Plc median 6.0 (4–7.5)
|
2
|
Partial (central) brain volume atrophy
rate
|
Neutral
|
Freedman et al.
|
MBP8298 IV
Placebo
|
612
|
SPMS
|
MBP 5.5 (1.0)
Plc 5.5 (1.1)
|
2
|
6 months confirmed EDSS progression
|
Neutral
|
Vermersch et al.
|
Masitinib
Placebo
|
35
|
SPMS
|
Mas 4.9 (1.2)
Plc 5.0 (1.1)
|
1
|
MSFC change from baseline
|
Neutral
|
Brochet et al.
|
Cyclophosphamide IV
Methlyprednisolone IV
|
138
|
SPMS
|
Not published by December 2016
|
2
|
Delay to confirmed EDSS progression
|
Neutral—high dropout rate
|
Zajicek et al.
|
Dronabinol
Placebo
|
498
|
SPMS
|
Dro 5.8 (0.7)
Plc 5.9 (0.7)
|
3
|
6 months confirmed EDSS progression,
change from baseline in MSIS29 physical
|
Neutral
|
Chataway et al.
|
Simvastatin
Placebo
|
140
|
SPMS
|
Sim 5.8 (0.8)
Plc 5.9 (0.8)
|
2
|
Mean annualised whole brain atrophy
rate
|
Positive
|
ASCEND
NCT01416181
|
Natalizumab IV
Placebo
|
889
|
SPMS
|
NTL 5.6 (0.9)
Plc 5.7 (0.9)
|
2
|
Confirmed progression in EDSS, T25FW,
9HPT
|
Neutral
|
Tourbah et al.
NCT02220933
|
Biotin
Placebo
|
154
|
PMS
|
Biotin 6.0 (0.8)
Plc 6.2 (0.5)
|
1
|
Improved EDSS or T25FW at 9 months
confirmed at 12 months
|
Positive
|
RIVITaLISe, 2016
NCT01212094
|
Rituximab intrathecal and IV
Placebo
|
43
|
SPMS
|
Not published by December 2016
|
2
|
Brain atrophy
|
Early termination for futility: did not
achieve CSF B cell depletion
|
Spain et al.
NCT01188811
|
Lipoic Acid
Placebo
|
54
|
SPMS
|
Lipoic acid median 5.5 (3–8)
Placebo median 6.0 (3–9)
|
2
|
Brain atrophy
|
Positive
|
EXPAND, 2016
NCT01665144
|
Siponimod (dose titration 0.25 mg to 2
mg)
Placebo
|
1649
|
SPMS
|
Not published by December 2016
|
3
|
Delay in time to confirmed EDSS
progression
|
Positive
|
Labels: #AAN2017, cladrabine, cyclosporin, Intravenous immunoglobulins, methotrexate, NHS, Primary Progressive MS, secondary progressive MS