Multiple Sclerosis and Related Disorders 1 (2012) 105
Contents lists available at SciVerse ScienceDirect
Multiple Sclerosis and Related Disorders journal homepage: www.elsevier.com/locate/msard
Editorial
Editors’ Welcome
The 3rd issue of Multiple Sclerosis and Related Disorders (MSARD) is full of diversity. Original manuscripts discuss the contribution of body mass index (BMI) to MS disability, there is a checklist for authors and reviewers of animal-based research, and analysis of the role for immune biomarkers in pediatric CNS inflammation. There is a critique of the role of B cells in MS, and the contribution of animal models in neuromyelitis optica, with invited commentary on several significant publications from 2011. One case report describes the rare association of interferon therapy with focal segmental glomerulonephritis, and another details a complex pediatric patient with an atypical clinical history of MS. The accrual of disability in MS is multifactorial. While many focus on relapse rate, lesion load, its distribution, and treatment response as determinants of disability. Pilutti et al. evaluate BMI influences disability. Using a questionnaire method and patient derived disability scores, the authors report that BMI remained static over the two year study period, while disability increased. Although BMI did not predict change in disability, over 50% of the cohort were overweight, a factor that may increase their risk of co-morbidities. Drs. Amor and Baker provide a ‘‘checklist’’ to aid in the scholarly review of publications concerning animal models. As pointed out by the authors, limitations in the translation of animal research to human trials may be due to fundamental differences in species, but may also be due to the design, conduct, interpretation or reporting of animal-based bench research. The guidelines are provided to aid researchers in considering the rigor of their work, and to enhance the thoroughness of review. Invited Commentaries in the present MSARD issue reflect on the role of measured disability and relapse rate to account for treatment effect and on the role of MRI detection of cortical lesions in clinical trials. Dr. Altmann evaluates the important paper produced by Sormani et al. (Neurology 2011) in which the authors demonstrate that the covariates (or composite endpoint), relapse rate and accumulation of new T2 lesions, entirely explained the treatment effect of interferon on disability accrual (as measured by the Expanded Disability Status Scale). Composite
2211-0348/$ - see front matter & 2012 Published by Elsevier B.V. http://dx.doi.org/10.1016/j.msard.2012.04.001
endpoints in trials are important as they have the potential to reduce the number of participants required to evaluate efficacy, although the combined endpoint must be appropriate to the therapeutic agent under investigation. In a second Commentary, Sormani et al. discuss one of their recently published manuscripts (PLoS One 2011) where they applied statistical modeling to determine the potential contribution of new cortical lesions (CL) as an outcome measure for clinical trials. A key consideration is whether it is of greater value to determine the total number of new CL per patient, or to evaluate the number of patients with no new CLs over a study period. The number of participants required for a two year trial of relapsing-remitting MS, powered on new CLs, was relatively small with only 50 participants per arm (assuming a trial design that compared a new therapeutic agent to interferon-beta or glatiramer acetate). The small number of participants required suggests that therapeutic inhibition of new CL formation may serve as a powerful outcome measure. A key next step will be to determine the clinical correlates that relate to surrogate endpoints, both those observed during a trial and after long term follow-up. In a comprehensive review of B cells in MS, Drs Pikor and Gommermann present emerging theories on the contribution of T-cell independent B cell activity as well as interactions between B cells and other arms of the immune system. The role of B cell activity, as it relates to antibodies as disease biomarkers or as indicators of disease activity are further discussed by Dale et al. in their review of pediatric CNS inflammation. The contribution of antibodies to disease is also explored in animal models of NMO, providing insights relevant to human disease. We hope you enjoy this current issue of MSARD, Sincerely Brenda Banwell, Gavin Giovannoni, Christopher Hawkes, Fred Lublin,
MD MD MD MD
Contents lists available at SciVerse ScienceDirect
Multiple Sclerosis and Related Disorders journal homepage: www.elsevier.com/locate/msard
Editorial
Editors’ Welcome
The 3rd issue of Multiple Sclerosis and Related Disorders (MSARD) is full of diversity. Original manuscripts discuss the contribution of body mass index (BMI) to MS disability, there is a checklist for authors and reviewers of animal-based research, and analysis of the role for immune biomarkers in pediatric CNS inflammation. There is a critique of the role of B cells in MS, and the contribution of animal models in neuromyelitis optica, with invited commentary on several significant publications from 2011. One case report describes the rare association of interferon therapy with focal segmental glomerulonephritis, and another details a complex pediatric patient with an atypical clinical history of MS. The accrual of disability in MS is multifactorial. While many focus on relapse rate, lesion load, its distribution, and treatment response as determinants of disability. Pilutti et al. evaluate BMI influences disability. Using a questionnaire method and patient derived disability scores, the authors report that BMI remained static over the two year study period, while disability increased. Although BMI did not predict change in disability, over 50% of the cohort were overweight, a factor that may increase their risk of co-morbidities. Drs. Amor and Baker provide a ‘‘checklist’’ to aid in the scholarly review of publications concerning animal models. As pointed out by the authors, limitations in the translation of animal research to human trials may be due to fundamental differences in species, but may also be due to the design, conduct, interpretation or reporting of animal-based bench research. The guidelines are provided to aid researchers in considering the rigor of their work, and to enhance the thoroughness of review. Invited Commentaries in the present MSARD issue reflect on the role of measured disability and relapse rate to account for treatment effect and on the role of MRI detection of cortical lesions in clinical trials. Dr. Altmann evaluates the important paper produced by Sormani et al. (Neurology 2011) in which the authors demonstrate that the covariates (or composite endpoint), relapse rate and accumulation of new T2 lesions, entirely explained the treatment effect of interferon on disability accrual (as measured by the Expanded Disability Status Scale). Composite
2211-0348/$ - see front matter & 2012 Published by Elsevier B.V. http://dx.doi.org/10.1016/j.msard.2012.04.001
endpoints in trials are important as they have the potential to reduce the number of participants required to evaluate efficacy, although the combined endpoint must be appropriate to the therapeutic agent under investigation. In a second Commentary, Sormani et al. discuss one of their recently published manuscripts (PLoS One 2011) where they applied statistical modeling to determine the potential contribution of new cortical lesions (CL) as an outcome measure for clinical trials. A key consideration is whether it is of greater value to determine the total number of new CL per patient, or to evaluate the number of patients with no new CLs over a study period. The number of participants required for a two year trial of relapsing-remitting MS, powered on new CLs, was relatively small with only 50 participants per arm (assuming a trial design that compared a new therapeutic agent to interferon-beta or glatiramer acetate). The small number of participants required suggests that therapeutic inhibition of new CL formation may serve as a powerful outcome measure. A key next step will be to determine the clinical correlates that relate to surrogate endpoints, both those observed during a trial and after long term follow-up. In a comprehensive review of B cells in MS, Drs Pikor and Gommermann present emerging theories on the contribution of T-cell independent B cell activity as well as interactions between B cells and other arms of the immune system. The role of B cell activity, as it relates to antibodies as disease biomarkers or as indicators of disease activity are further discussed by Dale et al. in their review of pediatric CNS inflammation. The contribution of antibodies to disease is also explored in animal models of NMO, providing insights relevant to human disease. We hope you enjoy this current issue of MSARD, Sincerely Brenda Banwell, Gavin Giovannoni, Christopher Hawkes, Fred Lublin,
MD MD MD MD
