Exit Strategy Patterns in Second-Line Therapies for Relapsing Forms of Multiple Sclerosis Publisher



Rezaei A ; Rezaeimanesh N ; Kohandel K ; Shahmohammadi S ; Jahani S ; Azimi A ; Naser Moghadasi A ; Sahraian MA
Source: Acta Neurologica Belgica Published:2026

Abstract

Background: Relapsing-remitting multiple sclerosis (RRMS) often necessitates treatment changes due to safety concerns, inadequate efficacy, or patient-specific factors. While second-line therapies (e.g., natalizumab, ocrelizumab) are effective, real-world evidence on outcomes after switching or discontinuing these therapies are limited, particularly in diverse healthcare settings. Objective: This study aimed to evaluate treatment transition patterns, reasons for discontinuation, and six-month clinical/MRI outcomes in patients with RRMS switching between second-line therapies or discontinuing treatment. Methods: A retrospective cohort study was conducted at Sina Hospital, Tehran, Iran, including 338 RRMS patients who switched or discontinued second-line therapies including fingolimod, natalizumab, ocrelizumab and rituximab. Clinical and MRI data were collected at baseline (therapy change/discontinuation) and six-month follow-up. Outcomes included relapse frequency, disability progression (Expanded Disability Status Scale [EDSS]), and MRI lesion activity. Statistical analysis was done using paired t-tests and descriptive statistics. Results: Among 338 patients (83.1% female, mean age 33.9 years), treatment transitions occurred most frequently to ocrelizumab (42.3%) or rituximab (33.4%). Safety concerns (32.0%), inadequate efficacy (29.9%), tolerability issues (13.6%), and pregnancy planning (8.9%) were primary reasons for therapy changes. Overall paired analyses of EDSS scores showed a strong correlation between pre- and post-switch measurements (r = 0.944, p < 0.001), although the average change for the entire cohort was minimal and not statistically significant. Notably, the subgroup of patients who switched from fingolimod to ocrelizumab demonstrated a statistically significant reduction in EDSS scores, with a mean difference of 0.19 (p = 0.019). Furthermore, among 110 patients whose treatment change was driven solely by inadequate efficacy (e.g., ongoing relapses or poor symptom control), the mean EDSS improved significantly from 2.41 (± 1.74) at baseline to 2.16 (± 1.80) at six months, with a mean difference of 0.25 (p < 0.001) and a strong correlation between baseline and follow-up scores (r = 0.92, p < 0.001). Conclusion: B-cell-depleting therapies, particularly ocrelizumab, may help lower disability in active RRMS, but longer follow-up is needed to confirm sustained benefits. Personalized strategies that balance efficacy, safety, and patient-specific factors (e.g., PML risk, pregnancy) are essential. Although most patients had low baseline disability, which may limit generalizability, these findings still offer real-world insight into treatment transitions. Longer prospective studies are needed to confirm long-term outcomes. © The Author(s) under exclusive licence to Belgian Neurological Society 2026.