Contributions
Abstract: P1856
Type: Poster
Abstract Category: Late breaking news
Introduction: Cerebrospinal fluid (CSF) concentrations of neurofilament light chain (NFL) and chitinase-3-like-1 (CHI3L1) have been proposed as prognostic biomarkers in multiple sclerosis (MS). Their prognostic value in unselected MS patients has, however, only been addressed in a few studies with a relatively low number of participants.
Study aim: To investigate the prognostic value of CSF concentrations of NFL and CHI3L1 in a cohort of newly diagnosed MS patients.
Material and methods: From January 2002 to December 2005 177 patients underwent lumbar puncture and were subsequently diagnosed with a clinically isolated syndrome (n=68) or relapsing-remitting MS (n=109) at our center. Patients were followed clinically with annual visits for untreated patients and six-monthly visits for patients treated with disease-modifying therapies. Data on baseline EDSS scores, relapses the preceding year, time to first relapse, onset of a secondary progressive disease course (SPMS) and EDSS at last follow-up visit were collected from patient files. CSF concentrations of NFL and CHI3L1 were measured in CSF by enzyme-linked immunosorbent assays.
Results: CSF concentrations of NFL were associated with relapse risk during the first two years of treatment (hazard ratio (HR) 1.22, 95% conficence interval (CI) 1.08-1.39 for a doubling of the CSF concentration of NFL). CSF concentrations of CHI3L1 were also associated with increased relapse risk (HR 1.63, 95% CI 1.05-2.53 for a doubling of NFL). However, in a multivariable analysis with CSF concentrations of CHI3L1, NFL and age, only the CSF concentration of NFL was significantly associated with relapse risk (hazard ratio 1.17, 95% CI 1.01-1.36 for a doubling of NFL).
Overall few patients converted to SPMS. Second-line treatment with natalizumab or mitoxantrone (hazard ratio 3.53, 95% CI 1.08-11.56) and increasing age (hazard ratio 1.06 per year of age, 95% CI 1.00-1.12) were independent risk factors for conversion to SPMS. CSF concentrations of NFL and CHI3L1 were not associated with the risk of conversion to SPMS. There was no relationship between the baseline CSF concentration of NFL or CHI3L1 and EDSS change per year for patients with at least five years of follow-up.
Conclusion: Baseline CSF concentrations of NFL were associated with short-term relapse risk but not with intermediate-term risk of SPMS or disability in an unselected cohort of newly diagnosed CIS and RRMS patients.
Disclosure: Finn Sellebjerg has served on scientific advisory boards, been on the steering committees of clinical trials, served as a consultant, received support for congress participation, received speaker honoraria, or received research support for his laboratory from Biogen, EMD Serono, Genzyme, Merck, Novartis, Roche, Sanofi and Teva. Per Soelberg Sørensen has received personal compensation from Biogen Idec, Merck Serono, Novartis, Genmab, TEVA, GSK, and Sanofi-aventis, Genzyme as member of scientific advisory boards, steering committees or independent data monitoring boards in clinical trials, or as speaker at meetings. His research unit has received research support from Biogen Idec, Bayer Schering, Merck Serono, TEVA, Sanofi-aventis, Novartis, RoFAR, Roche, and Genzyme, the Danish Multiple Sclerosis Society, the Danish Medical Research Council, and the European Union Sixth Framework Programme: Life sciences, Genomics and Biotechnology for health. Annette Bang Oturai has served on scientific advisory boards for Novartis, has received speaker honoraria from Biogen Idec, Merck Serono, and Novartis; and has received research support from the Danish Multiple Sclerosis Society, the Warwara Larsen Foundation and the Johnsen Foundation. Lydia Royen and Poul Erik Hyldgaard Jensen have nothing to disclose.
Abstract: P1856
Type: Poster
Abstract Category: Late breaking news
Introduction: Cerebrospinal fluid (CSF) concentrations of neurofilament light chain (NFL) and chitinase-3-like-1 (CHI3L1) have been proposed as prognostic biomarkers in multiple sclerosis (MS). Their prognostic value in unselected MS patients has, however, only been addressed in a few studies with a relatively low number of participants.
Study aim: To investigate the prognostic value of CSF concentrations of NFL and CHI3L1 in a cohort of newly diagnosed MS patients.
Material and methods: From January 2002 to December 2005 177 patients underwent lumbar puncture and were subsequently diagnosed with a clinically isolated syndrome (n=68) or relapsing-remitting MS (n=109) at our center. Patients were followed clinically with annual visits for untreated patients and six-monthly visits for patients treated with disease-modifying therapies. Data on baseline EDSS scores, relapses the preceding year, time to first relapse, onset of a secondary progressive disease course (SPMS) and EDSS at last follow-up visit were collected from patient files. CSF concentrations of NFL and CHI3L1 were measured in CSF by enzyme-linked immunosorbent assays.
Results: CSF concentrations of NFL were associated with relapse risk during the first two years of treatment (hazard ratio (HR) 1.22, 95% conficence interval (CI) 1.08-1.39 for a doubling of the CSF concentration of NFL). CSF concentrations of CHI3L1 were also associated with increased relapse risk (HR 1.63, 95% CI 1.05-2.53 for a doubling of NFL). However, in a multivariable analysis with CSF concentrations of CHI3L1, NFL and age, only the CSF concentration of NFL was significantly associated with relapse risk (hazard ratio 1.17, 95% CI 1.01-1.36 for a doubling of NFL).
Overall few patients converted to SPMS. Second-line treatment with natalizumab or mitoxantrone (hazard ratio 3.53, 95% CI 1.08-11.56) and increasing age (hazard ratio 1.06 per year of age, 95% CI 1.00-1.12) were independent risk factors for conversion to SPMS. CSF concentrations of NFL and CHI3L1 were not associated with the risk of conversion to SPMS. There was no relationship between the baseline CSF concentration of NFL or CHI3L1 and EDSS change per year for patients with at least five years of follow-up.
Conclusion: Baseline CSF concentrations of NFL were associated with short-term relapse risk but not with intermediate-term risk of SPMS or disability in an unselected cohort of newly diagnosed CIS and RRMS patients.
Disclosure: Finn Sellebjerg has served on scientific advisory boards, been on the steering committees of clinical trials, served as a consultant, received support for congress participation, received speaker honoraria, or received research support for his laboratory from Biogen, EMD Serono, Genzyme, Merck, Novartis, Roche, Sanofi and Teva. Per Soelberg Sørensen has received personal compensation from Biogen Idec, Merck Serono, Novartis, Genmab, TEVA, GSK, and Sanofi-aventis, Genzyme as member of scientific advisory boards, steering committees or independent data monitoring boards in clinical trials, or as speaker at meetings. His research unit has received research support from Biogen Idec, Bayer Schering, Merck Serono, TEVA, Sanofi-aventis, Novartis, RoFAR, Roche, and Genzyme, the Danish Multiple Sclerosis Society, the Danish Medical Research Council, and the European Union Sixth Framework Programme: Life sciences, Genomics and Biotechnology for health. Annette Bang Oturai has served on scientific advisory boards for Novartis, has received speaker honoraria from Biogen Idec, Merck Serono, and Novartis; and has received research support from the Danish Multiple Sclerosis Society, the Warwara Larsen Foundation and the Johnsen Foundation. Lydia Royen and Poul Erik Hyldgaard Jensen have nothing to disclose.