Author Of 2 Presentations
P0080 - Exploring neurofilament light in CSF as a biomarker for multiple sclerosis in clinical practice (ID 586)
Abstract
Background
Neurofilament light (NFL), a biomarker of axonal damage and disease activity in multiple sclerosis (MS), has been increasingly recognized for prognostic and therapeutic decisions.
Objectives
To assess the sensitivity and specificity of cerebrospinal fluid (CSF) NFL for disease activity and to evaluate its prognostic value in predicting disease severity and conversion from relapsing-remitting (RRMS) to secondary progressive MS (SPMS).
Methods
Patients with a confirmed diagnosis of RRMS (n=769) who had determined NFL in CSF as part of the diagnostic work-up or from assessments as part from regular clinical visits between 2001 and 2018 were retrospectively identified in the Swedish MS registry. Measurements over time of disease activity (clinical relapses and lesion formation on MRI) and disability (EDSS) were retrieved. We assessed NFL levels in relation to concomitant clinical and MRI activity and as outcome for treatment response.
Results
Patients with a concurrent clinical relapse had significantly higher NFL concentrations (median NFL no relapse 278 ng/L, relapsed 1122 ng/L, p<0.001) and a correlation with relapse severity was observed (p<0.001). Patients with gadolinium-enhancing lesions had higher median NFL levels (1414 ng/L) than those without (426 ng/L, p<0.001) and NFL levels correlated with the number of gadolinium enhancing lesions (p<0.001). CSF NFL showed sensitivity of 93.3% and specificity of 77.4% to disease activity (relapses and/or MRI activity). High NFL at diagnosis (n=414) was independently associated with worsening of disability and predicted progression to EDSS≥3 (n=128, p<0.001, HR 0.566 95% CI 0,413-0,711) and conversion to secondary progressive MS (n=39, p=0.0003, HR=0,380 95% CI 0,225-0,641). In a subset of patients (n=159), NFL was analysed at baseline and at follow-up (median time between LPs 23.7 months). Patients who switched from a first-line to a second-line therapy (n=65) exhibited significant reduction in NFL concentrations (p<0.001). However, patients who did not receive disease modifying therapy (DMT) (n=32), had first-line therapy (n=40), or switched to a third-line treatment (n=22) between baseline and follow-up did not show a significant decrease in their CSF NFL levels (p=0.975, p=0.658, and p=0.059 respectively).
Conclusions
Since 2001 CSF NFL has been part of the clinical assessment at Sahlgrenska University Hospital, Gothenburg. Thus, the results of this study are based on a real-life material and we can confirm the utility of NFL as a biomarker in MS. Our data underline NFL as a sensitive biomarker of disease activity, its usefulness for prediction of disability and clinical course and for monitoring DMT response. Serum/plasma NFL is most likely to show similar properties but probably at a lower precision.
P0187 - A prospective randomized open-label blinded endpoint multicenter non-inferiority study of oral cladribine and rituximab in Multiple Sclerosis (NOR-MS) (ID 1194)
Abstract
Background
Both induction therapy, like oral cladribine, and B-cell depletion therapy, like rituximab, are highly effective disease modulatory treatments (DMTs) in relapsing multiple sclerosis (MS). The high economic costs of the registered DMTs may limit availability of treatment and strain health budgets worldwide.
Oral cladribine is a recently approved DMT in Europe, while rituximab is used off-label, especially in Norway and Sweden. Large observational studies indicate good tolerance and treatment effects in MS and studies from other diseases indicate a good safety profile. However, to our knowledge, no phase three studies have compared rituximab with any established highly effective DMT. Formal safety data is also lacking for rituximab treatment in MS.
Objectives
To perform a prospective randomized open-label blinded endpoint multicenter non-inferiority study. The primary objective is to test whether rituximab is non-inferior to oral cladribine for treatment of relapsing MS.
Methods
In total 264 MS patients with relapsing MS will be recruited from 11 Norwegian centers and followed for 96 weeks. Inclusion criteria are having a relapsing MS diagnosis, age 18-65 years, at least one clinical relapse or one new T2 lesion on MRI within the last year and willingness to use contraception during the study period. Exclusion criteria are contraindications to either treatment, previous use of either or a similar treatment, or treatment with fingolimod or natalizumab (due to risk of rebound activity) within the last six months. The study participants will be treated with either cladribine or rituximab according to current guidelines.
Results
The primary endpoint is difference in number of new or enlarging T2 lesions between the two groups from rebaseline at 12 weeks to the end of the study at 96 weeks. Furthermore, we will study clinical course, blood samples and MRI biomarkers to provide tools for personalized MS treatment. Finally, the health economic consequences of these treatment options will be evaluated. At the time of abstract submission, 55 patients have been included across three study sites. The Covid19 outbreak unfortunately resulted in a temporary halt in inclusion from March to May 2020, but the study has now been reopened. End of study is estimated to fall 2023.
Conclusions
This study will guide clinicians and patients in future treatment choices for MS. The results will provide valuable knowledge concerning treatment strategies and can potentially have a huge impact on the costs of future MS treatments.