Dataset Information

Efficacy and safety of laquinimod in multiple sclerosis: current status.

ABSTRACT: Laquinimod is a novel immunomodulatory agent, in development as a potential disease-modifying treatment for multiple sclerosis (MS). Structurally related to linomide, its pharmacological predecessor, laquinimod combines anti-inflammatory and possibly clinically relevant neuroprotective effects with the convenience of oral administration. In this review we aim to highlight the immunomodulatory and neuroprotective effects of laquinimod, and to describe its effects in animal models of MS. Furthermore, we focus on current results of clinical studies in MS. Randomized, controlled clinical trials in relapsing MS demonstrate a dose-response effect on disease activity, measured by reduced clinical relapse rate, reduced number of brain MRI active lesions, as well as on sustained disability and brain atrophy. Laquinimod has a favourable tolerability and safety profile. A new phase III study, recently completed, will soon provide further details on the therapeutic potential of this drug. Laquinimod is a promising emerging treatment for relapsing-remitting MS that may provide a new therapeutic option in the near future.

SUBMITTER: Haggiag S

PROVIDER: S-EPMC3825117 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Efficacy and safety of laquinimod in multiple sclerosis: current status.

Haggiag Shalom S Ruggieri Serena S Gasperini Claudio C

Therapeutic advances in neurological disorders 20131101 6

Laquinimod is a novel immunomodulatory agent, in development as a potential disease-modifying treatment for multiple sclerosis (MS). Structurally related to linomide, its pharmacological predecessor, laquinimod combines anti-inflammatory and possibly clinically relevant neuroprotective effects with the convenience of oral administration. In this review we aim to highlight the immunomodulatory and neuroprotective effects of laquinimod, and to describe its effects in animal models of MS. Furthermo ...[more]

PMID: 24228070

Similar Datasets

Project description:BackgroundIn this pooled, post hoc analysis of a phase 2 trial and the phase 3 TEMSO, TOWER, and TENERE clinical trials, long-term efficacy and safety of teriflunomide were assessed in subgroups of patients with relapsing multiple sclerosis (MS) defined by prior treatment status.MethodsPatients were classified according to their prior treatment status in the core and core plus extension periods. In the core period, patients were grouped according to treatment status at the start of the study: treatment naive (no prior disease-modifying therapy [DMT] or DMT > 2 years prior to randomization), previously treated with another DMT (DMT > 6 to ≤24 months prior to randomization), and recently treated with another DMT (DMT ≤6 months prior to randomization). In the core plus extension period, patients were re-baselined to the time of starting teriflunomide 14 mg and grouped according to prior treatment status at that time point. Efficacy endpoints included annualized relapse rate (ARR), probability of confirmed disability worsening (CDW) over 12 weeks, and Expanded Disability Status Scale (EDSS) score. The incidence of adverse events was also assessed.ResultsMost frequently received prior DMTs at baseline were glatiramer acetate and interferon beta-1a across treatment groups. Teriflunomide 14 mg significantly reduced ARR versus placebo in the core period, regardless of prior treatment status. In the core and extension periods, adjusted ARRs were low (0.193-0.284) in patients treated with teriflunomide 14 mg across all subgroups. Probability of CDW by Year 4 was similar across subgroups; by Year 5, the percentage of patients with 12-week CDW was similar in treatment-naive patients and patients recently treated with another DMT (33.9 and 33.7%, respectively). EDSS scores were stable over time in all prior-treatment subgroups. There were no new or unexpected safety signals. Limitations include selective bias due to patient attrition, variability in subgroup size, and lack of magnetic resonance imaging outcomes.ConclusionsThe efficacy and safety of teriflunomide 14 mg was similar in all patients with relapsing MS, regardless of prior treatment history.Trial registrationPhase 2 trial core: NCT01487096 ; Phase 2 trial extension: NCT00228163 ; TEMSO core: NCT00134563 ; TEMSO extension: NCT00803049 ; TOWER: NCT00751881 ; TENERE: NCT00883337 .

Project description:Development of effective treatments requires understanding of disease mechanisms. For diseases of the central nervous system (CNS), such as multiple sclerosis (MS), human pathology studies and animal models tend to identify candidate disease mechanisms. However, these studies cannot easily link the identified processes to clinical outcomes, such as MS severity, required for causality assessment of candidate mechanisms. Technological advances now allow the generation of thousands of biomarkers in living human subjects, derived from genes, transcripts, medical images, and proteins or metabolites in biological fluids. These biomarkers can be assembled into computational models of clinical value, provided such models are generalizable. Reproducibility of models increases with the technical rigor of the study design, such as blinding, control implementation, the use of large cohorts that encompass the entire spectrum of disease phenotypes and, most importantly, model validation in independent cohort(s). To facilitate the growth of this important research area, we performed a meta-analysis of publications (n = 302) that model MS clinical outcomes extracting effect sizes, while also scoring the technical quality of the study design using predefined criteria. Finally, we generated a Shiny-App-based website that allows dynamic exploration of the data by selective filtering. On average, the published studies fulfilled only one of the seven criteria of study design rigor. Only 15.2% of the studies used any validation strategy, and only 8% used the gold standard of independent cohort validation. Many studies also used small cohorts, e.g., for magnetic resonance imaging (MRI) and blood biomarker predictors, the median sample size was <100 subjects. We observed inverse relationships between reported effect sizes and the number of study design criteria fulfilled, expanding analogous reports from non-MS fields, that studies that fail to limit bias overestimate effect sizes. In conclusion, the presented meta-analysis represents a useful tool for researchers, reviewers, and funders to improve the design of future modeling studies in MS and to easily compare new studies with the published literature. We expect that this will accelerate research in this important area, leading to the development of robust models with proven clinical value.

Dataset Information

Efficacy and safety of laquinimod in multiple sclerosis: current status.

Publications

Efficacy and safety of laquinimod in multiple sclerosis: current status.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets