Plasma neurofilament light levels segregate treatment effects: results from the IMSE studies with multiple disease modulatory drugs
ECTRIMS Online Library. Delcoigne B. 10/11/18; 231954; 205
Bénédicte Delcoigne
Bénédicte Delcoigne
Contributions
Abstract

Abstract: 205

Type: Scientific Session

Abstract Category: Therapy - Tools for detecting therapeutic response

Background: Plasma neurofilament light (NfL) levels correlate with clinical and neuroradiological disease activity in relapsing-remitting MS (RRMS) patients, and are lowered in patients starting disease modifying treatment (DMT). However, comparisons across multiple DMTs in real world populations are lacking.
Objective: To measure the dynamics of NfL in plasma samples from patients initiating DMT from the Swedish observational study Immunomodulation and Multiple Sclerosis Epidemiology (IMSE).
Method: We obtained samples at start and at one year (range 9-15 months) from 915 RRMS patients on teriflunomide (TERI, n=100), fingolimod (FGL, n=253), dimethyl fumarate (DMF, n=314) or natalizumab (NTZ, n=248). In addition, 1026 population-based controls served to calculate age-adjusted NfL values. NfL was determined using the Single Molecule Array (SimoaTM) NF-light® Advantage kit. Linear models were used to analyse log(NfL) values in relation to clinical variables and multinomial logistic analysis to model probability to start different DMTs.
Results: Patients starting NTZ were younger, had higher baseline NfL values, higher number of relapses the year before start and higher expanded disability status scale (EDSS) scores compared to patients starting TERI. The FGL and DMF groups were in between these two. Age-adjusted baseline NfL values were associated to the number of previous relapses (coefficientrelapses=0.16, p< 0.001). Change in NfL from baseline to 12 months was influenced by baseline NfL (explaining 20% of variance), DMT (explaining 10%) and age (explaining 4%). The log(NfL) value at 12 months was mainly influenced by the baseline value (coefficientBL_NfL=0.30, p< 0.001) and DMT (coefficientNTZ=-0.27, p< 0.001; coefficientDMF=-0.22, p < 0.001; coefficientFGL=-0.18, p< 0.001, TERI being the reference).
Conclusion: Age-adjusted baseline NfL values were associated with number of previous relapses, in turn having a significant impact on levels at 12 months, suggesting a slow degree of normalization or lingering disease activity at 12 months. Adjusted for baseline levels, on-treatment NfL levels were significantly lower with NTZ, DMF and FGL as compared to TERI, due to a more pronounced decrease in NfL levels. Additional data on effect of rituximab and alemtuzumab, as well as the predictive value of NfL for measures of future disease development will be presented. These findings support the notion of using NfL for monitoring treatment effects in RRMS.
Disclosure: Ali Manouchehrinia has received speaker honoraria from Biogen.
Fredrik Piehl has received research grants from Biogen, Novartis, and Genzyme, and fees for serving as Chair of DMC in clinical trials with Parexel.
Christian Barro received travel support by Teva and Novartis not related to this work.
Ludwig Kappo's institution (University Hospital Basel) has received in the last 3 years and used exclusively for research support: Steering committee, advisory board, and consultancy fees from Actelion, Addex, Bayer HealthCare, Biogen Idec, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera, Siemens, Teva, UCB, and Xenoport; speaker fees from Bayer HealthCare, Biogen Idec, Merck, Novartis, Sanofi, and Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, and Teva; license fees for Neurostatus products; and grants from Bayer HealthCare, Biogen Idec, European Union, Merck, Novartis, Roche Research Foundation, Swiss MS Society, and the Swiss National Research Foundation.
Jens Kuhle received speaker fees, research support, travel support, and/or served on advisory boards by ECTRIMS, Swiss MS Society, Swiss National Research Foundation, (320030_160221), University of Basel, Bayer, Biogen, Genzyme, Merck, Novartis, Protagen AG, Roche, Teva.
Jens Kuhle's institution (University Hospital Basel) received and used exclusively for research support: consulting fees from Biogen, Novartis, Protagen AG, Roche, Teva; speaker fees from the Swiss MS Society, Biogen, Novartis, Roche, Genzyme; travel expenses from Merck Serono, Novartis, Roche; grants from ECTRIMS Research Fellowship Programme, University of Basel, Swiss MS Society, Swiss National Research Foundation (320030_160221), Bayer AG, Biogen, Genzyme, Merck, Novartis, Roche.
Tatiana Plavina and Bernd C Kieseier are employees of and hold stock/stock options in Biogen.
Jon Tsai is an employee of Sanofi Genzyme.
David Leppert is an employee of Novartis.
Tomas Olsson has received unrestricted MS research grants and/or lecture/advisory board honoraria from Biogen, Novartis, Genzyme, Roche and Merck.
Bénédicte Delcoigne: nothing to disclose
Zuzanna Michalak: nothing to disclose
Lars Alfredsson: nothing to disclose
Ingrid Kockum: nothing to disclose
Novartis, Sanofi Genzyme and Biogen funded this study

Abstract: 205

Type: Scientific Session

Abstract Category: Therapy - Tools for detecting therapeutic response

Background: Plasma neurofilament light (NfL) levels correlate with clinical and neuroradiological disease activity in relapsing-remitting MS (RRMS) patients, and are lowered in patients starting disease modifying treatment (DMT). However, comparisons across multiple DMTs in real world populations are lacking.
Objective: To measure the dynamics of NfL in plasma samples from patients initiating DMT from the Swedish observational study Immunomodulation and Multiple Sclerosis Epidemiology (IMSE).
Method: We obtained samples at start and at one year (range 9-15 months) from 915 RRMS patients on teriflunomide (TERI, n=100), fingolimod (FGL, n=253), dimethyl fumarate (DMF, n=314) or natalizumab (NTZ, n=248). In addition, 1026 population-based controls served to calculate age-adjusted NfL values. NfL was determined using the Single Molecule Array (SimoaTM) NF-light® Advantage kit. Linear models were used to analyse log(NfL) values in relation to clinical variables and multinomial logistic analysis to model probability to start different DMTs.
Results: Patients starting NTZ were younger, had higher baseline NfL values, higher number of relapses the year before start and higher expanded disability status scale (EDSS) scores compared to patients starting TERI. The FGL and DMF groups were in between these two. Age-adjusted baseline NfL values were associated to the number of previous relapses (coefficientrelapses=0.16, p< 0.001). Change in NfL from baseline to 12 months was influenced by baseline NfL (explaining 20% of variance), DMT (explaining 10%) and age (explaining 4%). The log(NfL) value at 12 months was mainly influenced by the baseline value (coefficientBL_NfL=0.30, p< 0.001) and DMT (coefficientNTZ=-0.27, p< 0.001; coefficientDMF=-0.22, p < 0.001; coefficientFGL=-0.18, p< 0.001, TERI being the reference).
Conclusion: Age-adjusted baseline NfL values were associated with number of previous relapses, in turn having a significant impact on levels at 12 months, suggesting a slow degree of normalization or lingering disease activity at 12 months. Adjusted for baseline levels, on-treatment NfL levels were significantly lower with NTZ, DMF and FGL as compared to TERI, due to a more pronounced decrease in NfL levels. Additional data on effect of rituximab and alemtuzumab, as well as the predictive value of NfL for measures of future disease development will be presented. These findings support the notion of using NfL for monitoring treatment effects in RRMS.
Disclosure: Ali Manouchehrinia has received speaker honoraria from Biogen.
Fredrik Piehl has received research grants from Biogen, Novartis, and Genzyme, and fees for serving as Chair of DMC in clinical trials with Parexel.
Christian Barro received travel support by Teva and Novartis not related to this work.
Ludwig Kappo's institution (University Hospital Basel) has received in the last 3 years and used exclusively for research support: Steering committee, advisory board, and consultancy fees from Actelion, Addex, Bayer HealthCare, Biogen Idec, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera, Siemens, Teva, UCB, and Xenoport; speaker fees from Bayer HealthCare, Biogen Idec, Merck, Novartis, Sanofi, and Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, and Teva; license fees for Neurostatus products; and grants from Bayer HealthCare, Biogen Idec, European Union, Merck, Novartis, Roche Research Foundation, Swiss MS Society, and the Swiss National Research Foundation.
Jens Kuhle received speaker fees, research support, travel support, and/or served on advisory boards by ECTRIMS, Swiss MS Society, Swiss National Research Foundation, (320030_160221), University of Basel, Bayer, Biogen, Genzyme, Merck, Novartis, Protagen AG, Roche, Teva.
Jens Kuhle's institution (University Hospital Basel) received and used exclusively for research support: consulting fees from Biogen, Novartis, Protagen AG, Roche, Teva; speaker fees from the Swiss MS Society, Biogen, Novartis, Roche, Genzyme; travel expenses from Merck Serono, Novartis, Roche; grants from ECTRIMS Research Fellowship Programme, University of Basel, Swiss MS Society, Swiss National Research Foundation (320030_160221), Bayer AG, Biogen, Genzyme, Merck, Novartis, Roche.
Tatiana Plavina and Bernd C Kieseier are employees of and hold stock/stock options in Biogen.
Jon Tsai is an employee of Sanofi Genzyme.
David Leppert is an employee of Novartis.
Tomas Olsson has received unrestricted MS research grants and/or lecture/advisory board honoraria from Biogen, Novartis, Genzyme, Roche and Merck.
Bénédicte Delcoigne: nothing to disclose
Zuzanna Michalak: nothing to disclose
Lars Alfredsson: nothing to disclose
Ingrid Kockum: nothing to disclose
Novartis, Sanofi Genzyme and Biogen funded this study

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