Long-term comparative analysis of no evidence of disease activity (NEDA-3) status between multiple sclerosis patients treated with natalizumab and fingolimod for up to 4 years

Abstract

Background Comparative effectiveness of natalizumab and fingolimod over a follow-up longer than 2 years has been not addressed yet. Objectives To compare the effect on no evidence of disease activity (NEDA-3) in relapsing-remitting multiple sclerosis (RRMS) patients treated with natalizumab or fingolimod for at least 4 years. Methods We included RRMS patients switched from first-line agents to natalizumab or fingolimod. Patients were propensity score (PS)-matched on a 1-to-1 basis. Percentages of patients reaching NEDA-3 status at 2 and 4 years of follow-up were compared using the chi-square test. The risk of not achieving NEDA-3 at 4 years was explored in matched samples by Cox regression models. Results We evaluated 174 PS-matched patients. Patients receiving natalizumab reached a NEDA-3 status at 2 and 4 years more frequently than those exposed to fingolimod (63% vs 44%, p=0.037; 45.7% vs 25.8%, p=0.015, respectively). Patients receiving natalizumab were at a significant lower risk of not achieving the NEDA-3 status at 4 years compared to those exposed to fingolimod (hazard ratio (95% confidence interval): 0.54 (0.36–0.80), p=0.002). Conclusions Although both medications were effective in patients non-responding to first-line agents, natalizumab seems to be superior to fingolimod in RRMS in obtaining NEDA-3 status at 4 years.

Use of natalizumab in persons with multiple sclerosis: 2022 update

“…Real-world cohorts of persons with RRMS from single centers, multicenters, and national and international registries have been well utilized to explore the comparative effectiveness of natalizumab with another highly effective DMT, fingolimod, across clinical, radiological, disability, and disease activity outcomes (Barbin et al, 2016;Baroncini et al, 2016;Boziki et al, 2021;Braune et al, 2013;Curti et al, 2019;Guerra et al, 2021;Kalincik et al, 2015;Koch-Henriksen et al, 2017;Prosperini et al, 2017). The majority of these studies have shown natalizumab to be superior to fingolimod with regard to ARR, proportion of PwMS relapsing at 1 and 2 years and over longer time periods, short-term disability improvement, and proportions of PwMS with gadolinium (Gd)-enhancing lesions or new T2 lesions at 1 and 2 years (Barbin et al, 2016;Baroncini et al, 2016;Boziki et al, 2021;Kalincik et al, 2015).…”

“…The majority of these studies have shown natalizumab to be superior to fingolimod with regard to ARR, proportion of PwMS relapsing at 1 and 2 years and over longer time periods, short-term disability improvement, and proportions of PwMS with gadolinium (Gd)-enhancing lesions or new T2 lesions at 1 and 2 years (Barbin et al, 2016;Baroncini et al, 2016;Boziki et al, 2021;Kalincik et al, 2015). Several studies use the metric of "no evidence of disease activity (NEDA) encompassing the absence of three clinical/imaging markers (NEDA-3)" -i.e., absence of relapses, no new radiological activity, and no confirmed disability progression (Wong et al, 2018) have shown a significantly higher proportion of PwMS treated with natalizumab than fingolimod achieved NEDA-3 at 2 years, with one study extending this observation to 4 years (Baroncini et al, 2016;Curti et al, 2019;Guerra et al, 2021;Prosperini et al, 2017).…”

Self‐injectable DMTs in relapsing MS: NEDA assessment at 10 years in a real‐world cohort

“…Unfortunately, a decrease in NEDA-3 rates is frequently seen, even with high-efficacy DMTs. 23 In another study evaluating the NEDA status of 306 patients during their 3-year follow-up, the reason why NEDA could not be sustained in 64% of cases was evaluated due to MRI activity and one of the most important results of this study is the importance of intermittent imaging checks even in clinically stable MS patients (huhn et al, 2019). While only the presence of attack, MRI activity only, or progression in EDSS may be seen in patients unable to achieve NEDA-3, the course can also be observed with impairment in two or three parameters.…”

“…A study evaluating NEDA‐3 status in the second and fourth years of fingolimod and natalizumab therapies reported higher NEDA‐3 rates at two years, with a significant decrease in the fourth year. Unfortunately, a decrease in NEDA‐3 rates is frequently seen, even with high‐efficacy DMTs 23 . In another study evaluating the NEDA status of 306 patients during their 3‐year follow‐up, the reason why NEDA could not be sustained in 64% of cases was evaluated due to MRI activity and one of the most important results of this study is the importance of intermittent imaging checks even in clinically stable MS patients (huhn et al, 2019).…”

Comparative effectiveness of natalizumab and fingolimod and injectable therapies in patients with pediatric multiple sclerosis: A registry-based retrospective cohort study

“…The copyright holder for this preprint this version posted October 13, 2022. ; https://doi.org/10.1101/2022.10.12.22280969 doi: medRxiv preprint the consistent results of the analyses of relapse outcomes in these 2 treatment groups suggests natalizumab could be superior to fingolimod on relapse outcomes. This is supported by relapse outcomes from comparative studies of natalizumab and fingolimod in patients with pediatric-or adult-onset MS. 38,[47][48][49] It is highly likely that lower relapse rates would also be associated with lower brain and spinal cord lesion accumulation, with potential for differential long-term benefits. In particular, cognitive and productivity outcomes, and risk of secondary progressive MS are potentially reduced with maximal control of the early inflammatory phase of RRMS.…”