Baseline characteristics associated with NEDA-3 status in fingolimod-treated patients with relapsing-remitting multiple sclerosis

Abstract

Background: Fingolimod is an efficacious treatment for relapsing-remitting multiple sclerosis (RRMS) and there is class I evidence that it is superior to standard care in reducing relapse rate. However, real-world data investigating its effectiveness and potential predictors of response are still scarce. Objective: To estimate (i) the proportion of fingolimod-treated patients who achieved the no evidence of disease activity (NEDA-3) status; and (ii) to determine which baseline (i.e. at treatment start) clinical and magnetic resonance imaging (MRI) variables were associated with better outcomes. Methods: We collected clinical and MRI data of RRMS patients treated with fingolimod and followed-up for 24 months. The proportion of patients who had NEDA-3 -i.e. absence of relapses, sustained Expanded Disability Status Scale (EDSS) worsening and radiological activity on MRI -was estimated. A Cox proportional hazard model was carried out to investigate which baseline characteristics were associated with the NEDA status at follow-up. Results: We collected data of 201 patients who started fingolimod. Of them, 24 (12%) were treatment-naïve, 115 (58%) were switched after failing a self-injectable drug, and 60 (30%) switching from natalizumab. Five patients who discontinued fingolimod early (within 3 months) (bradycardia, n = 2; leukopaenia, n = 2; macular oedema, n = 1) were removed from the analysis. At follow-up, 118 (60%) patients achieved the NEDA-3 status, while 78 experienced clinical and/or MRI activity. The risk of not achieving the NEDA-3 status was associated with higher baseline EDSS score (hazard ratio [HR] = 1.18, p = 0.024) and more relapses in the 12 months prior to fingolimod start (HR = 1.61, p = 0.014). Conclusion: Our findings suggest that fingolimod may lead to a better control of the disease if started in patients with a less aggressive disease (i.e. fewer pre-treatment relapses and milder disability level), thus supporting its possible role as an early treatment for MS.

Assessing ‘No Evidence of Disease Activity’ Status in Patients with Relapsing-Remitting Multiple Sclerosis Receiving Fingolimod in Routine Clinical Practice: A Retrospective Analysis of the Multiple Sclerosis Clinical and Magnetic Resonance Imaging Outcomes in the USA (MS-MRIUS) Study

“…The presence of disability progression at baseline significantly reduced the proportion of patients who achieved NEDA-4, but not NEDA-3, status during fingolimod treatment. The baseline characteristics that affected NEDA-3 status in the present study differ from that of a single-center real-world study, which demonstrated that patients with more relapses or a higher EDSS score at baseline were at increased risk of not achieving NEDA-3 status 2 years after fingolimod initiation [ 23 ]. The difference between our study and that of Giuliani et al may reflect differences in the patient populations being assessed and the criteria according to which stratification was performed.…”

“…However, the methodology for collecting and analyzing MRI data was not always reported so it was not clear whether MRI outcomes were assessed using a standardized methodology [ 16 ]. Furthermore, few real-world studies have evaluated the impact of baseline disease activity on the proportion of patients able to achieve NEDA status during fingolimod treatment [ 23 ]. A need exists for robust real-world studies that generate high-quality clinical and MRI data, including for BVL, to assess the effectiveness of fingolimod with regard to patients achieving NEDA-3 and NEDA-4 status.…”

Efficacy of alemtuzumab in relapsing-remitting MS patients who received additional courses after the initial two courses: Pooled analysis of the CARE-MS, extension, and TOPAZ studies

“…Product labeling since 2018 provides the opportunity to tailor cumulative dosage based on an individual patient's needs. Recent studies suggesting higher relapse activity before treatment may indicate increased likelihood of disease activity with treatment; 18,[26][27][28] however, baseline disease activity in the 3-, 4-, and ⩾5-courses groups were similar to the 2-courses group, except for higher baseline Gd-enhancing lesion counts in the 4-and ⩾5-courses groups.…”

Efficacy of alemtuzumab over 6 years in relapsing–remitting multiple sclerosis patients who relapsed between courses 1 and 2: Post hoc analysis of the CARE-MS studies

“…Disease activity soon after initiating a DMT does not necessarily represent treatment failure. 20 Studies of other DMTs have shown that pretreatment relapse activity is predictive of on-treatment disease activity, including relapses, 21 – 23 suggesting a higher underlying propensity for disease activity in some patients. This is supported in our study by the finding that, compared with patients without relapse between Courses 1 and 2, early relapsers had a higher mean number of relapses in the 1−2 years before study entry and a higher baseline mean EDSS score.…”