Laquinimod for multiple sclerosis.
Topic: Immunotherapy

Multiple sclerosis (MS) is a chronic immune-mediated, inflammatory, demyelinating, neurodegenerative disorder of the central nervous system, and it causes major socioeconomic burden for the individual patient and for society. An inflammatory pathology occurs during the early relapsing stage of MS and a neurodegenerative pathology dominates the later progressive stage of the disease. Not all MS patients respond adequately to currently available disease-modifying drugs (DMDs). Alternative MS treatments with new modes of action are required to expand the current options for disease-modifying therapies (DMTs) and to aim for freedom from relapses, inflammatory lesions, disability progression and neurodegeneration. Laquinimod has dual properties of immunomodulation and neuroprotection and is a potentially promising new oral DMD in the treatment of relapsing MS.

PICO
Population: Patients with multiple sclerosis
Intervention: Laquinimod treatment
Comparison: Currently available disease-modifying drugs
Outcomes: Reduction in relapses, inflammatory lesions, disability progression, and neurodegeneration

Included studies:
title: Verification of the operator model of learning. Frequency of trajectories.
title: Treatment with laquinimod reduces development of active MRI lesions in relapsing MS.
abstract: Laquinimod is a novel immunomodulatory substance developed as an orally available disease modifying treatment in multiple sclerosis (MS). The purpose of this study was to evaluate safety, tolerability, and efficacy on MRI lesions of two different doses of laquinimod compared with placebo in patients with relapsing MS.
title: The socioeconomic consequences of multiple sclerosis: a controlled national study.
abstract: Multiple sclerosis (MS) has serious negative effects on health-, social-, and work-related issues for the patients and their families, thus causing significant socioeconomic burden. The objective of the study was to determine healthcare costs and indirect illness costs in MS patient in a national sample. We used all national records from the Danish National Patient Registry (1998-2006), and identified 10,849 MS patients which were compared with 43,396 randomly age-, sex- and social matched citizens. Healthcare sector costs included frequencies and costs of hospitalizations and weighted outpatient use, frequencies of visits and hospitalizations and costs from primary sectors, and the use and costs of drugs. Productivity costs (the value of lost productivity from time off from work due to illness) and all social transfer payments were also calculated. Patients with MS had significantly higher rates of health-related contact and medication use and very low employment rate which incurred a higher socioeconomic cost. The income level of employed MS patients was significantly lower than that of control subjects. The annual total health sector costs and productivity costs were €14,575 for MS patients vs. €1163 for control subjects (p<0.001), corresponding to an annual mean excess health-related cost of €13,413 for each patient with MS. In addition, the MS patients received an annual mean excess social transfer income of €6843. MS present social and economical consequences more than eight years before diagnosis. We conclude that MS causes major socioeconomic consequences for the individual patient and for society. Productivity costs are a far more important economic factor, especially due to reduced employment, which are enhanced by the early age of diagnose onset.
title: Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis.
abstract: Interferon beta is widely prescribed to treat multiple sclerosis (MS); however, its relationship with disability progression has yet to be established.
title: Effect of laquinimod on MRI-monitored disease activity in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study.
abstract: A 24-week phase II trial has shown that 0.3 mg of laquinimod given daily to patients with relapsing-remitting multiple sclerosis was well tolerated and reduced the formation of active lesions. We assessed the effect of oral daily 0.3 and 0.6 mg laquinimod on MRI-monitored disease activity in a 36-week double-blind, placebo-controlled phase IIb study.
title: Magnetization transfer imaging of acute black holes in patients on glatiramer acetate.
abstract: The aim of this study was to determine evolution of T1 unenhanced hypointense lesions (acute or chronic black holes (ABHs, CBHs)) by measuring their magnetization transfer ratio (MTR) changes over 12 months. 40 glatiramer acetate (GA)-naive patients with relapsing-remitting MS who presented with 1 or more contrast-enhancing lesions (CELs) at baseline underwent 1.5-T MRI at baseline and after 12 months. Lesions were classified into 4 patterns based on differences in lesion isointensity or hypointensity over 12 months. Of 115 CELs detected at baseline, 64, after 12 months, followed pattern A (isointense-isointense), 6 pattern B (isointense-hypointense), 33 pattern C (hypointense-isointense), and 12 pattern D (hypointense-hypointense). MTR significantly increased for all unenhanced T1 hypointense lesions (p = 0.02). Highest MTR increases were observed for patterns C (ABHs +18.2 %, p less than 0.001) and D (CBHs +34.2 %, p = 0.023), but significant improvement was also detected for pattern A (+1.4 %, p = 0.046); no significant MTR changes were found for pattern B. GA treatment significantly recovered MTR in ABHs and CBHs, possibly indicating a greater potential for remyelination.
title: 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.
abstract: Laquinimod, an oral novel immunomodulator, was shown to reduce MRI-measured disease activity in relapsing-remitting MS (RRMS) patients.
title: Placebo-controlled trial of oral laquinimod for multiple sclerosis.
abstract: Two proof-of-concept clinical trials have provided evidence that laquinimod reduces disease activity in patients with relapsing-remitting multiple sclerosis.
title: New acute and chronic black holes in patients with multiple sclerosis randomised to interferon beta-1b or glatiramer acetate.
abstract: Hypointense lesions on T1 weighted MRI, referred to as black holes (BH), are a marker of demyelination/axonal loss in multiple sclerosis (MS). There is some evidence that glatiramer acetate (GA) may decrease the conversion of new brain lesions to BH.