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Randomized Controlled Trial
. 2024 Jul 15:462:123102.
doi: 10.1016/j.jns.2024.123102. Epub 2024 Jun 22.

Influence of personalized extended interval dosing on the natalizumab wearing-off effect - a sub-study of the NEXT-MS trial

A A Toorop  1 , M H J Wessels  1 , L M Y Gelissen  1 , E Hoitsma  2 , E M P E Zeinstra  3 , L C van Rooij  4 , C E P van Munster  5 , A Vennegoor  6 , J P Mostert  7 , B H A Wokke  8 , N F Kalkers  9 , E L J Hoogervorst  10 , J J J van Eijk  11 , C M Roosendaal  12 , J J Kragt  13 , M Eurelings  14 , J van Genugten  15 , J Nielsen  16 , L G F Sinnige  17 , M E Kloosterziel  18 , E P J Arnoldus  19 , G W van Dijk  20 , W H Bouvy  21 , E M M Strijbis  1 , B W van Oosten  1 , B A de Jong  1 , B I Lissenberg-Witte  22 , T Rispens  23 , B M J Uitdehaag  1 , J Killestein  1 , Z L E van Kempen  24
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Free article
Randomized Controlled Trial

Influence of personalized extended interval dosing on the natalizumab wearing-off effect - a sub-study of the NEXT-MS trial

A A Toorop et al. J Neurol Sci. .
Free article

Abstract

Background and objectives: Wearing-off symptoms during natalizumab treatment in multiple sclerosis are characterized by an increase of MS-related symptoms prior to natalizumab administration. The influence of extended interval dosing (EID) on wearing-off symptoms are important to consider, as this might cause hesitancy in initiating or continuing EID.

Methods: Participants of the NEXT-MS trial, in which treatment intervals are adjusted based on drug concentrations, were divided into two groups: an extended group containing participants with at least one week of additional interval extension, and a group with a fixed interval during the trial (range 4-7 weeks). Changes in the occurrence, frequency, onset, and severity of wearing-off symptoms were evaluated.

Results: 255 participants were included (extended group n = 171, fixed group n = 84). The odds on occurrence of wearing-off symptoms in the extended group did not increase after extending the treatment interval. Additional analyses for frequency, onset, and severity of wearing-off symptoms showed no changes over time. Mean decrease in natalizumab drug concentration did not influence the frequency of wearing-off symptoms.

Discussion: Wearing-off symptoms were not reinforced by further extending the natalizumab interval. Wearing-off symptoms might increase in a minority of patients after EID, although our data support the view that wearing-off symptoms appear to be unrelated to the decrease in natalizumab trough drug concentrations.

Keywords: Extended interval dosing; Multiple sclerosis; Natalizumab; Wearing-off.

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Conflict of interest statement

Declaration of competing interest A.A. Toorop: nothing to disclose. M.H.J. Wessels: nothing to disclose. L.M.Y. Gelissen: nothing to disclose. E. Hoitsma: has accepted (speaker and congress) fees from Merck Serono, Biogen Idec, Roche, and Sanofi Genzyme. E.M.P.E. Zeinstra: reports advisory boards/consultancy fees for Merck, Novartis, Genzyme and Roche. L.C. van Rooij: nothing to disclose. C.E.P. van Munster: nothing to disclose. A. Vennegoor: nothing to disclose. J.P. Mostert: nothing to disclose. B.H.A. Wokke: nothing to disclose. N.F. Kalkers: nothing to disclose. E.L.J. Hoogervorst: nothing to disclose. J.J.J. van Eijk: reports honoraria for advisory boards and/or speakers fee from Merck Serono, Biogen Idec, Sanofi Genzyme, Roche and Novartis. C.M. Roosendaal: nothing to disclose. J.J. Kragt: nothing to disclose. M. Eurelings: nothing to disclose. J. Nielsen: nothing to disclose. J. van Genugten: nothing to disclose. L.G.F. Sinnige: nothing to disclose. M.E. Kloosterziel: nothing to disclose. E.P.J. Arnoldus: nothing to disclose. G.W. van Dijk: nothing to disclose. W.H. Bouvy: nothing to disclose. E.M.M. Strijbis: nothing to disclose. B.W. van Oosten: nothing to disclose. B.A. de Jong: nothing to disclose. B.I. Lissenberg-Witte: nothing to disclose. T. Rispens received funding for research from Genmab and consultancy fees from Novartis. B.M.J. Uitdehaag: reports research support and/or consultancy fees from Genzyme, Biogen Idec, Novartis, Teva Pharmaceutical Industries, Merck Serono, Roche, and Immunic Therapeutics. J. Killestein: received research grants for multicentre investigator initiated trials DOT-MS trial, ClinicalTrials.gov Identifier: NCT04260711 (ZonMW) and BLOOMS trial (ZonMW and Treatmeds), ClinicalTrials.gov Identifier: NCT05296161); received consulting fees for F. Hoffmann-La Roche Ltd., Biogen, Teva, Merck, Novartis and Sanofi/Genzyme (all payments to institution); reports speaker relationships with F. Hoffmann-La Roche Ltd., Biogen, Immunic, Teva, Merck, Novartis and Sanofi/Genzyme (all payments to institution); adjudication committee of MS clinical trial of Immunic (payments to institution only). Z.L.E. van Kempen: nothing to disclose.

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