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Background: We aimed to determine the association of clinical and routine cerebrospinal fluid biochemical markers (total protein, IgG index and oligoclonal bands) with disability in multiple sclerosis and whether these biomarkers assessed at diagnosis add prognostic value., Methods: We followed a cohort of patients included in the Multiple Sclerosis Lorraine Register (eastern France) who had a diagnosis of multiple sclerosis for at least 5 years, as well as biological markers values and MRI findings (Barkhof's criteria). In a Cox regression model, endpoint was time to score of 4 on the Expanded Disability Status Scale (EDSS) (i.e., limited time walking without aid or rest for more than 500 m)., Results: For 407 patients included, the median time from multiple sclerosis onset to EDSS score 4 was 4.5 years [2.2-7.2]. Cerebrospinal fluid total protein factor < 500 mg/L was associated with EDSS score 4 on bivariate analysis (hazard ratio 0.66, 95% confidence interval 0.46-0.95, p = 0.02). On multivariate analysis, older age at disease onset (≥50 years) and initial primary progressive course of MS but not biological markers predicted worse prognosis., Conclusion: Routine cerebrospinal fluid biological markers at diagnosis were not prognostic factors of multiple sclerosis progression.

Background: The clinical impact of neutralizing antibodies against interferon-beta (NAb) is controversial. Their presence can lead to a decrease in interferon-beta (IFNβ) 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 IFNβ, NAb and fatigue., Methods: Patients with relapsing-remitting MS on IFNβ treatment were included. During the second year of treatment, the patients were analyzed for NAb status and non-response criteria to IFNβ (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., Results: Of the 176 patients included: 22.3% were NAb positive, 54.5% presented non-response criteria to IFNβ, 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 IFNβ (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)., Conclusions: This study demonstrates the impact of NAb on the non-clinical response to IFNβ. Fatigue assessment is an indicator of IFNβ responsiveness and a predictive biomarker of deterioration on patient's neurological status.