Neutralizing antibodies and fatigue as predictors of low response to interferon-beta treatment in patients with multiple sclerosis.

Philippe Manceau 1, * Clotilde Latarche 2 Sophie Pittion 1 Gilles Edan 3, 4, 5 Jérôme de Sèze 6 Catherine Massart 4, 7 Marc Debouverie 8, 1, 2
* Corresponding author
3 VisAGeS - Vision, Action et Gestion d'informations en Santé
INSERM - Institut National de la Santé et de la Recherche Médicale : U746, Inria Rennes – Bretagne Atlantique , IRISA-D5 - SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE
8 Ecole de Santé Publique [Nancy]
Faculté de Médecine [Nancy]
Abstract : BackgroundThe clinical impact of neutralizing antibodies against interferon-beta (NAb) is controversial. Their presence can lead to a decrease in interferon-beta (IFNß) efficacy. Fatigue reported in patients with multiple sclerosis (MS) may be associated with an unfavorable clinical course. We conducted a prospective multicentre study to assess the association between response to IFNß, NAb and fatigue.MethodsPatients with relapsing-remitting MS on IFNß treatment were included. During the second year of treatment, the patients were analyzed for NAb status and non-response criteria to IFNß (number of relapses ¿1 during the follow-up period, increase in the Expanded Disability Status Scale ¿0.5). The score on the Modified Fatigue Impact Scale (MFIS pathological if score ¿35) was noted for each patient.ResultsOf the 176 patients included: 22.3% were NAb positive, 54.5% presented non-response criteria to IFNß, and 57.4% had a pathological MFIS score. Fatigue was increased in NAb¿+¿patients (p¿=¿0.0014) and they were more likely to present non-response criteria to IFNß (p¿=¿0.041) than NAb- patients. Multivariate logistic regression analysis showed that the presence of NAb was related to fatigue (p¿=¿0.0032) and denoted disease activity in these patients (p¿=¿0.026).ConclusionsThis study demonstrates the impact of NAb on the non-clinical response to IFNß. Fatigue assessment is an indicator of IFNß responsiveness and a predictive biomarker of deterioration on patient¿s neurological status.
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Philippe Manceau, Clotilde Latarche, Sophie Pittion, Gilles Edan, Jérôme de Sèze, et al.. Neutralizing antibodies and fatigue as predictors of low response to interferon-beta treatment in patients with multiple sclerosis.. BMC Neurology, BioMed Central, 2014, 14 (1), pp.215. ⟨10.1186/s12883-014-0215-y⟩. ⟨inserm-01103114v2⟩

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