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)

1 Service de neurologie [CHRU Nancy]
2 CIC - Centre d'investigation clinique [Nancy]
3 VisAGeS - Vision, Action et Gestion d'informations en Santé
4 CIC - Centre d'Investigation Clinique [Rennes]
5 Service de Neurologie [CHU Rennes]
6 Service de neurologie [Strasbourg]
7 Service d'Hormonologie
8 Ecole de Santé Publique [Nancy]

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.

Mots clés: Interferon-beta; Fatigue; Response to treatment; Neutralizing antibodies; Multiple sclerosis

Domaines: Sciences du Vivant [q-bio]; Neurosciences [q-bio.NC]

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, 2014, 14 (1), pp.215. ⟨10.1186/s12883-014-0215-y⟩. ⟨inserm-01103114v2⟩