Oral laquinimod in patients with relapsing-remitting multiple sclerosis: 36-week double-blind active extension of the multi-centre, randomized, double-blind, parallel-group placebo-controlled study

2010 ◽  
Vol 16 (11) ◽  
pp. 1360-1366 ◽  
Author(s):  
G. Comi ◽  
O Abramsky ◽  
T Arbizu ◽  
A Boyko ◽  
R Gold ◽  
...  
Keyword(s):  
Liver Enzymes ◽  
Extension Phase ◽  
Controlled Study ◽  
Safety Signal ◽  
Double Blind ◽  
Clinical Assessments ◽  
Parallel Group ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Efficacy Profile

Background: Laquinimod, an oral novel immunomodulator, was shown to reduce MRI-measured disease activity in relapsing—remitting MS (RRMS) patients. Objectives: To determine whether the safety and efficacy profile of laquinimod, as shown in a placebo-controlled 36-week trial (LAQ/5062), is sustained and reproducible. Methods: Two hundred and fifty seven patients entered the extension phase in which MRI was performed at the beginning and at the end of the active extension phase. Clinical assessments were performed at weeks 4, 12 and every 12 weeks thereafter. Results: Two hundred and thirty nine (93%) patients completed the extension phase and 222 (86.3%) had a final scan available. Gadolinium-enhanced (GdE) T1 lesions were significantly reduced for patients switching from placebo to 0.3/ 0.6 mg doses (52%, p = 0.0006). In patients initially randomized to 0.6 mg in LAQ/5062 the reduction of MRI activity observed in the placebo-controlled phase was maintained in the extension. The proportion of GdE-free patients for those who switched from placebo increased from a baseline of 31% to 47% at the end of the extension phase ( p = 0.01). The most prominent safety signal was elevations of liver enzymes, reversible in all cases. Conclusions: The good efficacy and the excellent safety and tolerability profiles of laquinimod 0.6 mg/day are confirmed in this extension study.

Randomized, double-blind, placebo-controlled study of subcutaneous interferon beta-1a in relapsing-remitting multiple sclerosis: a categorical disability trend analysis

2002 ◽  
Vol 8 (1) ◽  
pp. 10-14 ◽  
Author(s):  
C Liu ◽  
L D Blumhardt
Keyword(s):  
Multiple Sclerosis ◽  
Disease Duration ◽  
Significant Proportion ◽  
Phase Iii ◽  
Controlled Study ◽  
Double Blind ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Immunomodulatory Therapies

The treatment effects of recent immunomodulatory therapies on disease progression in relapsing-remitting multiple sclerosis (MS) have been mostly established from ‘confirmed progression’ endpoints. However, the reliability of this outcome measure is poor and a significant proportion of patients may be erroneously classified. We previously proposed the area under disability/time curves to quantify in-trial disability changes, but although these have advantages, they lack information on the direction of change. We have therefore performed disease trend analyses and categorical classifications using serial Expanded Disability Status Scale (EDSS) scores from the 533 complete datasets in a double-blind, randomized, placebo-controlled, phase III trial of subcutaneous interferon β-1a (IFNβ-1a) (PRISMS study). We found significant treatment benefits for IFNβ-1a on in-trial disability course (P=0.002). Therapeutic advantages remained when relapse-related assessments were excluded (P=0.018). Post hoc analyses demonstrated that IFNβ-1a was mainly effective in both increasing the proportion of patients with a ‘stable’ course and reducing those with prolonged, disabling deteriorations. Baseline disease duration and EDSS levels, but not MRI lesion load, predicted the subsequent disability trends. Mean ‘numbers needed to treat’ (NNTs) to obtain preferred disability courses were reduced in patients with shorter disease duration. These results have important implications for the targeting of immunomodulatory therapies in MS.

Randomized, double-blind, placebo-controlled study of subcutaneous interferon beta-Ia in relapsing-remitting multiple sclerosis: a categorical disability trend analysis

2002 ◽  
Vol 8 (1_suppl) ◽  
pp. 10-14 ◽  
Author(s):  
C. Liu ◽  
LD Blumhardt
Keyword(s):  
Multiple Sclerosis ◽  
Disease Duration ◽  
Significant Proportion ◽  
Phase Iii ◽  
Controlled Study ◽  
Double Blind ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Immunomodulatory Therapies

The treatment effects of recent immunomodulatory therapies on disease progression in relapsing-remitting multiple sclerosis (MS) have been mostly established from 'confirmed progression' endpoints. However, the reliability of this outcome measure is poor and a significant proportion of patients may be erroneously classified. We previously proposed the area under disability/time curves to quantify in-trial disability changes, but although these have advantages, they lack information on the direction of change. We have therefore performed disease trend analyses and categorical classifications using serial Expanded Disability Status Scale (EDSS) scores from the 533 complete datasets in a double-blind, randomized, placebo-controlled, phase III trial of subcutaneous interferon β-1a (IFNβ-1a) (PRISMS study). We found significant treatment benefits for IFNβ-1a on in-trial disability course (P=0.002). Therapeutic advantages remained when relapse-related assessments were excluded (P=0.018). Post hoc analyses demonstrated that IFNβ-la was mainly effective in both increasing the proportion of patients with a 'stable' course and reducing those with prolonged, disabling deteriorations. Baseline disease duration and EDSS levels, but not MRI lesion load, predicted the subsequent disability trends. Mean 'numbers needed to treat' (NNTs) to obtain preferred disability courses were reduced in patients with shorter disease duration. These results have important implications for the targeting of immunomodulatory therapies in MS. Multiple Sclerosis (2002) 8, 10-14

Glatiramer acetate in combination with minocycline in patients with relapsing—remitting multiple sclerosis: results of a Canadian, multicenter, double-blind, placebo-controlled trial

2009 ◽  
Vol 15 (10) ◽  
pp. 1183-1194 ◽  
Author(s):  
LM Metz ◽  
D. Li ◽  
A. Traboulsee ◽  
ML Myles ◽  
P. Duquette ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Glatiramer Acetate ◽  
Controlled Trial ◽  
Controlled Study ◽  
Combination Group ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Minocycline is proposed as an add-on therapy to improve the efficacy of glatiramer acetate in relapsing—remitting multiple sclerosis. The effect of minocycline plus glatiramer acetate was evaluated in this double-blind, placebo-controlled study by determining the total number of T1 gadolinium-enhanced lesions at months 8 and 9 in patients who were starting glatiramer acetate and had at least one T1 gadolinium-enhanced lesion on screening magnetic resonance imaging. Forty-four participants were randomized to either minocycline 100 mg twice daily or matching placebo for 9 months as add-on therapy. They were assessed at screening and months 1, 3, 6, 8 and 9. Forty participants completed the study. Compared with glatiramer acetate/placebo, glatiramer acetate/minocycline reduced the total number of T1 gadolinium-enhanced lesions by 63% (mean 1.47 versus 2.95; p = 0.08), the total number of new and enlarging T2 lesions by 65% (mean 1.84 versus 5.14; p = 0.06), and the total T2 disease burden (p = 0.10). A higher number of gadolinium-enhanced lesions were present in the glatiramer acetate/minocycline group at baseline; this was incorporated into the analysis of the primary endpoint but makes interpretation of the data more challenging. The risk of relapse tended to be lower in the combination group (0.19 versus 0.41; p = NS). Treatment was safe and well tolerated. We conclude that efficacy endpoints showed a consistent trend favoring combination treatment. As minocycline is a relatively safe oral therapy, further study of this combination is warranted in relapsing—remitting multiple sclerosis.

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