Abstract
ObjectiveTo determine factors (including the role of specific disease modulatory treatments [DMTs]) associated with (1) baseline, (2) on-treatment, and (3) change (from treatment start to on-treatment assessment) in plasma neurofilament light chain (pNfL) concentrations in relapsing-remitting multiple sclerosis (RRMS).MethodsData including blood samples analyses and long-term clinical follow-up information for 1,261 Swedish patients with RRMS starting novel DMTs were analyzed using linear regressions to model pNfL and changes in pNfL concentrations as a function of clinical variables and DMTs (alemtuzumab, dimethyl fumarate, fingolimod, natalizumab, rituximab, and teriflunomide).ResultsThe baseline pNfL concentration was positively associated with relapse rate, Expanded Disability Status Scale score, Age-Related MS Severity Score, and MS Impact Score (MSIS-29), and negatively associated with Symbol Digit Modalities Test performance and the number of previously used DMTs. All analyses, which used inverse propensity score weighting to correct for differences in baseline factors at DMT start, highlighted that both the reduction in pNfL concentration from baseline to on-treatment measurement and the on-treatment pNfL level differed across DMTs. Patients starting alemtuzumab displayed the highest reduction in pNfL concentration and lowest on-treatment pNfL concentrations, while those starting teriflunomide had the smallest decrease and highest on-treatment levels, but also starting from lower values. Both on-treatment pNfL and decrease in pNfL concentrations were highly dependent on baseline concentrations.ConclusionChoice of DMT in RRMS is significantly associated with degree of reduction in pNfL, which supports a role for pNfL as a drug response marker.
Highlights
Data including blood samples analyses and long-term clinical follow-up information for 1,261 Swedish patients with relapsingremitting multiple sclerosis (RRMS) starting novel diseasemodifying therapies (DMT) were analyzed using linear regressions to model plasma neurofilament light chain (pNfL) and changes in pNfL concentrations as a function of clinical variables and disease-modifying therapies (DMTs)
Choice of DMT in RRMS is significantly associated with degree of reduction in pNfL, which supports a role for pNfL as a drug response marker
Podcast Dr David Lapides talks with Dr Frederik Piehl about his paper discussing how blood neurofilament light levels segregate treatment effects in multiple sclerosis
Summary
Data including blood samples analyses and long-term clinical follow-up information for 1,261 Swedish patients with RRMS starting novel DMTs were analyzed using linear regressions to model pNfL and changes in pNfL concentrations as a function of clinical variables and DMTs (alemtuzumab, dimethyl fumarate, fingolimod, natalizumab, rituximab, and teriflunomide). Patient selection and sample collection The Immunomodulation and Multiple Sclerosis Epidemiology study (IMSE) is a comprehensive nationwide Swedish postapproval program of patients starting newer MS DMTs, coupled with sampling of blood at initiation of therapy and at follow-up. We analyzed data for 1,139 patients with RRMS initiating alemtuzumab (ALM, n = 89), dimethyl fumarate (DMF, n = 339), fingolimod (FGL, n = 275), natalizumab (NTZ, n = 284), or teriflunomide (TFL, n = 152). A follow-up program similar to IMSE was recently started for rituximab (RTX); only 11 of 122 analyzed patients had a sample before starting therapy. A total of 1,026 populationbased controls included in the study by Manouchehrinia et al. was used to calculate age-adjusted pNfL reference curves
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