Contributions
Abstract: P857
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Introduction: Clinically isolated syndrome (CIS) is a first episode of neurological symptoms suggestive of inflammatory demyelinating central nervous system (CNS) disease. The majority of CIS patients will develop a second clinical event or new demyelinating lesions in the cranial MRI (cMRI) and will therefore be diagnosed with multiple sclerosis (MS). Evidence suggests that early disease modifying treatment (DMT) reduces the risk of conversion to MS in CIS patients. However DMTs are costly and can cause side effects. A reliable identification of patients who will convert to MS would hence be helpful for early treatment decisions. The aim of this study was to identify putative differences in the metabolome of CIS patients with early conversion versus CIS patients who did not develop MS.
Methods: Serum samples of 80 CIS patients were included in this monocentric pilot study in a case-control design: 40 patients who converted to MS as defined by clinical or cMRI progression within two years were compared to 40 age- and sex-matched control patients without conversion to MS in the respective follow up period. The samples were analyzed by mass spectrometry using the Biocrates AbsoluteIDQ p180 kit. Of 188 metabolites, 139 remained after quality control, one sample was excluded by outlier detection. Significant differences between the two groups were evaluated by a t test followed by adjustment for multiple testing using the Benjamini-Hochberg procedure.
Results: Of the 79 CIS patients included, 58 (73 %) were female; the mean age at sampling was 36.4 years. The mean time from disease manifestation to sampling was 10 months, 17 patients (21%) received DMT. The groups did not differ significantly regarding sex, age at diagnosis, treatment status or recent relapse/corticosteroid treatment. After correction for multiple testing, no significant differences in the metabolome of CIS patients with or without conversion to MS within two years could be detected.
Discussion: In this pilot study none of the 139 analyzed metabolites showed significant differences between CIS patients who evolved to MS within two years after diagnosis and patients who remained as CIS. Larger cohorts or sampling at multiple time points could be needed to detect small differences between metabolites in the blood of CIS patients with or without early conversion to MS. A prospective approach would facilitate better correction for treatment status and other relevant clinical parameters.
Disclosure: CG reports no conflicts of interest
SS is employed by BIOCRATES Life Sciences AG.
MMH reports travel grants and honoraria from Biogen Idec, Merck Serono, Bayer Health Care
BH has served on scientific advisory boards for F. Hoffmann-La Roche Ltd, Novartis, Bayer AG, and Genentech; he has served as DMSC member for AllergyCare and TG Therapeutics; he or his institution have received speaker honoraria from Biogen Idec, Teva Neuroscience, Merck Serono, Medimmune, Novartis, Desitin, and F. Hoffmann-La Roche Ltd; his institution has received research support from Chugai Pharmaceuticals and Hoffmann-La-Roche; holds part of two patents; one for the detection of antibodies and T cells against KIR4.1 in a subpopulation of MS patients and one for genetic determinants of neutralizing antibodies to interferon β.
AB reports personal fees from Biogen, Merck Serono, Mylan, Novartis, Roche, Sanofi Genzyme, and Teva, and compensations for clinical trials from Alexion Pharmaceuticals, Biogen, Novartis, Genzyme, Roche, and Teva - all outside the submitted work.
Abstract: P857
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Introduction: Clinically isolated syndrome (CIS) is a first episode of neurological symptoms suggestive of inflammatory demyelinating central nervous system (CNS) disease. The majority of CIS patients will develop a second clinical event or new demyelinating lesions in the cranial MRI (cMRI) and will therefore be diagnosed with multiple sclerosis (MS). Evidence suggests that early disease modifying treatment (DMT) reduces the risk of conversion to MS in CIS patients. However DMTs are costly and can cause side effects. A reliable identification of patients who will convert to MS would hence be helpful for early treatment decisions. The aim of this study was to identify putative differences in the metabolome of CIS patients with early conversion versus CIS patients who did not develop MS.
Methods: Serum samples of 80 CIS patients were included in this monocentric pilot study in a case-control design: 40 patients who converted to MS as defined by clinical or cMRI progression within two years were compared to 40 age- and sex-matched control patients without conversion to MS in the respective follow up period. The samples were analyzed by mass spectrometry using the Biocrates AbsoluteIDQ p180 kit. Of 188 metabolites, 139 remained after quality control, one sample was excluded by outlier detection. Significant differences between the two groups were evaluated by a t test followed by adjustment for multiple testing using the Benjamini-Hochberg procedure.
Results: Of the 79 CIS patients included, 58 (73 %) were female; the mean age at sampling was 36.4 years. The mean time from disease manifestation to sampling was 10 months, 17 patients (21%) received DMT. The groups did not differ significantly regarding sex, age at diagnosis, treatment status or recent relapse/corticosteroid treatment. After correction for multiple testing, no significant differences in the metabolome of CIS patients with or without conversion to MS within two years could be detected.
Discussion: In this pilot study none of the 139 analyzed metabolites showed significant differences between CIS patients who evolved to MS within two years after diagnosis and patients who remained as CIS. Larger cohorts or sampling at multiple time points could be needed to detect small differences between metabolites in the blood of CIS patients with or without early conversion to MS. A prospective approach would facilitate better correction for treatment status and other relevant clinical parameters.
Disclosure: CG reports no conflicts of interest
SS is employed by BIOCRATES Life Sciences AG.
MMH reports travel grants and honoraria from Biogen Idec, Merck Serono, Bayer Health Care
BH has served on scientific advisory boards for F. Hoffmann-La Roche Ltd, Novartis, Bayer AG, and Genentech; he has served as DMSC member for AllergyCare and TG Therapeutics; he or his institution have received speaker honoraria from Biogen Idec, Teva Neuroscience, Merck Serono, Medimmune, Novartis, Desitin, and F. Hoffmann-La Roche Ltd; his institution has received research support from Chugai Pharmaceuticals and Hoffmann-La-Roche; holds part of two patents; one for the detection of antibodies and T cells against KIR4.1 in a subpopulation of MS patients and one for genetic determinants of neutralizing antibodies to interferon β.
AB reports personal fees from Biogen, Merck Serono, Mylan, Novartis, Roche, Sanofi Genzyme, and Teva, and compensations for clinical trials from Alexion Pharmaceuticals, Biogen, Novartis, Genzyme, Roche, and Teva - all outside the submitted work.