Contributions
Abstract: P1176
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: There is a persisting need for clinically meaningful prognostic and disease activity biomarkers in patients with early multiple sclerosis (MS).
Objectives: To analyse the association of intrathecal immunoglobulin (Ig)M production with conversion to definite MS in patients with a CIS and to explore the association of intrathecal IgM production with age and radiological findings in CIS/early relapsing-remitting (RR)MS.
Methods: Comprehensive CSF data, including calculated percentage intrathecal IgM and IgG production and oligoclonal IgG bands (OCB), were collected in a prospective cohort of 150 patients with CIS/early RRMS, which were regularly assessed clinically and by brain magnetic resonance imaging (MRI). Cox proportional hazard models were used to analyse associations of different variables in patients with CIS (n = 94, median follow-up 727 days) with risk of conversion to definite MS according to the McDonald 2010 criteria.
Results: An intrathecal IgM production >0% occurred in 23.2% of patients (33/142), who were on average 5 years younger at onset of first symptoms than patients without an intrathecal IgM production (median: 27 vs. 32 years, p = 0.011). Patients with CIS/early RRMS with an intrathecal IgM production had a higher frequency of infratentorial MRI lesions than patients without an intrathecal IgM production (56.3% vs. 33.3%, p = 0.034). In multivariable Cox regression analysis, CIS patients with an intrathecal IgM production had a higher risk for conversion to definite MS (HR = 3.47, CI = 1.72 - 7.03, p = 0.001) than CIS patients without an intrathecal IgM production after adjustment for age (HR = 0.96, CI = 0.92 - 0.996, p = 0.03), OCB (HR = 0.96, CI = 0.36 - 2.59, p = 0.936) and the number of T2-weighted lesions (log-transformed, HR = 1.55, CI = 1.10 - 2.17, p = 0.012).
Conclusion: Intrathecal IgM production is a strong independent risk factor for conversion to MS in patients with a CIS. Furthermore, intrathecal IgM production is associated with a younger onset age and a higher frequency of infratentorial MRI lesions in CIS/early RRMS. Thus, an intrathecal IgM production may represent a clinically meaningful prognostic and disease activity biomarker in early MS.
Disclosure: CP: nothing to disclose. UG: nothing to disclose. RMG received financial support for travel and congress attendance from Novartis. MS: nothing to disclose. JRB: nothing to disclose. LR: nothing to disclose. FCP: nothing to disclose. AUB served on the scientific advisory board for Biogen; received travel funding and/or speaker honoraria from Novartis and Biogen; has patents pending from method and system for optic nerve head shape quantification, perceptive visual computing based postural control analysis, multiple sclerosis biomarker, and perceptive sleep motion analysis; has consulted for Nexus and Motognosis; and received research support from Novartis Pharma, Biogen Idec, BMWi, BMBF, and Guthy Jackson Charitable Foundation. JBS has received travel grants and speaking fees from Bayer Healthcare, Biogen Idec, Merck Serono, sanofi-aventis/Genzyme, Teva Pharmaceuticals, and Novartis. FP serves on the scientific advisory board for Novartis; received speaker honoraria and travel funding from Bayer, Novartis, Biogen Idec, Teva, Sanofi-Aventis/Genzyme, Merck Serono, Alexion, Chugai, MedImmune, and Shire; consulted for SanofiGenzyme, Biogen Idec, MedImmune, Shire, and Alexion; and received research support from Bayer, Novartis, Biogen Idec, Teva, Sanofi-Aventis/Genzyme, Alexion, Merck Serono, German Research Council, Werth Stiftung of the City of Cologne, German Ministry of Education and Research, Arthur Arnstein Stiftung Berlin, EU FP7 Framework Program, Arthur Arnstein Foundation Berlin, Guthy Jackson Charitable Foundation, and National Multiple Sclerosis of the USA. KR was supported by the German Ministry of Education and Research (BMBF/KKNMS, Competence Network Multiple Sclerosis) and has received research support from Novartis and Merck Serono as well as speaking fees and travel grants from Guthy Jackson Charitable Foundation, Bayer Healthcare, Biogen Idec, Merck Serono, sanofi-aventis/Genzyme, Teva Pharmaceuticals, Roche and Novartis. JO received travel grants from Bayer healthcare, Novartis and Biogen.
Abstract: P1176
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: There is a persisting need for clinically meaningful prognostic and disease activity biomarkers in patients with early multiple sclerosis (MS).
Objectives: To analyse the association of intrathecal immunoglobulin (Ig)M production with conversion to definite MS in patients with a CIS and to explore the association of intrathecal IgM production with age and radiological findings in CIS/early relapsing-remitting (RR)MS.
Methods: Comprehensive CSF data, including calculated percentage intrathecal IgM and IgG production and oligoclonal IgG bands (OCB), were collected in a prospective cohort of 150 patients with CIS/early RRMS, which were regularly assessed clinically and by brain magnetic resonance imaging (MRI). Cox proportional hazard models were used to analyse associations of different variables in patients with CIS (n = 94, median follow-up 727 days) with risk of conversion to definite MS according to the McDonald 2010 criteria.
Results: An intrathecal IgM production >0% occurred in 23.2% of patients (33/142), who were on average 5 years younger at onset of first symptoms than patients without an intrathecal IgM production (median: 27 vs. 32 years, p = 0.011). Patients with CIS/early RRMS with an intrathecal IgM production had a higher frequency of infratentorial MRI lesions than patients without an intrathecal IgM production (56.3% vs. 33.3%, p = 0.034). In multivariable Cox regression analysis, CIS patients with an intrathecal IgM production had a higher risk for conversion to definite MS (HR = 3.47, CI = 1.72 - 7.03, p = 0.001) than CIS patients without an intrathecal IgM production after adjustment for age (HR = 0.96, CI = 0.92 - 0.996, p = 0.03), OCB (HR = 0.96, CI = 0.36 - 2.59, p = 0.936) and the number of T2-weighted lesions (log-transformed, HR = 1.55, CI = 1.10 - 2.17, p = 0.012).
Conclusion: Intrathecal IgM production is a strong independent risk factor for conversion to MS in patients with a CIS. Furthermore, intrathecal IgM production is associated with a younger onset age and a higher frequency of infratentorial MRI lesions in CIS/early RRMS. Thus, an intrathecal IgM production may represent a clinically meaningful prognostic and disease activity biomarker in early MS.
Disclosure: CP: nothing to disclose. UG: nothing to disclose. RMG received financial support for travel and congress attendance from Novartis. MS: nothing to disclose. JRB: nothing to disclose. LR: nothing to disclose. FCP: nothing to disclose. AUB served on the scientific advisory board for Biogen; received travel funding and/or speaker honoraria from Novartis and Biogen; has patents pending from method and system for optic nerve head shape quantification, perceptive visual computing based postural control analysis, multiple sclerosis biomarker, and perceptive sleep motion analysis; has consulted for Nexus and Motognosis; and received research support from Novartis Pharma, Biogen Idec, BMWi, BMBF, and Guthy Jackson Charitable Foundation. JBS has received travel grants and speaking fees from Bayer Healthcare, Biogen Idec, Merck Serono, sanofi-aventis/Genzyme, Teva Pharmaceuticals, and Novartis. FP serves on the scientific advisory board for Novartis; received speaker honoraria and travel funding from Bayer, Novartis, Biogen Idec, Teva, Sanofi-Aventis/Genzyme, Merck Serono, Alexion, Chugai, MedImmune, and Shire; consulted for SanofiGenzyme, Biogen Idec, MedImmune, Shire, and Alexion; and received research support from Bayer, Novartis, Biogen Idec, Teva, Sanofi-Aventis/Genzyme, Alexion, Merck Serono, German Research Council, Werth Stiftung of the City of Cologne, German Ministry of Education and Research, Arthur Arnstein Stiftung Berlin, EU FP7 Framework Program, Arthur Arnstein Foundation Berlin, Guthy Jackson Charitable Foundation, and National Multiple Sclerosis of the USA. KR was supported by the German Ministry of Education and Research (BMBF/KKNMS, Competence Network Multiple Sclerosis) and has received research support from Novartis and Merck Serono as well as speaking fees and travel grants from Guthy Jackson Charitable Foundation, Bayer Healthcare, Biogen Idec, Merck Serono, sanofi-aventis/Genzyme, Teva Pharmaceuticals, Roche and Novartis. JO received travel grants from Bayer healthcare, Novartis and Biogen.