Disease Exacerbation after the Cessation of Fingolimod Treatment in Japanese Patients with Multiple Sclerosis

Abstract

Objective In Japan, following the launch of dimethyl fumarate (DMF) after fingolimod as a disease-modifying drug in multiple sclerosis (MS), some patients switched from fingolimod to DMF. The aim of this study was to determine the follow-up status of MS patients who switched to DMF after fingolimod cessation. Methods Clinical and magnetic resonance imaging (MRI) data in 19 patients with MS who switched to DMF were collected for at least for 6 months after fingolimod cessation. Results Ten patients (52.6%) experienced clinical or MRI exacerbation after fingolimod cessation. The peripheral blood lymphocyte counts at the time of fingolimod cessation in those with disease exacerbation were significantly lower than in those without exacerbation. The patients with disease exacerbation were further classified into three groups based on MRI findings: those with some new T2-weighted lesions with or without gadolinium (Gd) enhancement (group I), those with more new and/or enlarged T2-weighted lesions with Gd enhancement compared to pre-fingolimod induction (group II), and those with multifocal tumefactive demyelinating lesions. In group II, the clinical disease activity, which was similar to that at fingolimod initiation in group I, was higher than the clinical disease activity observed before fingolimod initiation. Conversely, group III exhibited unexpected new MRI findings that were not evident before fingolimod initiation. Conclusion Cessation of fingolimod might precipitate rebound or reactivation of clinical disease in patients with MS, and careful follow-up is necessary for patients who discontinue fingolimod.

Fingolimod Rebound: A Review of the Clinical Experience and Management Considerations

“…Reported cases of unexpected increases in clinical and MRI activity after discontinuation of fingolimod began accumulating in 2012 [10,[25][26][27][28][29][30][31][32][33][34][35], with some including reports of tumefactive lesions on MRI [36][37][38][39][40]. While these cases exhibit a significant amount of clinical heterogeneity, a recently published case series has demonstrated three different MRI patterns of post-fingolimod rebound: tumefactive lesions, a punctated pattern with innumerable small T2 and gadolinium (Gd)enhancing lesions, and a pattern more typical of classical MS [40].…”

Severe rebound relapse of multiple sclerosis after switching from fingolimod to dimethyl fumarate

“…In contrast, cases of severe MS rebound after fingolimod withdrawal have recently been reported . A recent study also reported that 10 of 19 Japanese MS patients who switched fingolimod to DMF showed clinical or radiological exacerbation, and three of these 10 patients developed multifocal tumefactive lesions . Patients with high disease activity before fingolimod treatment might be predisposed to severe rebound syndrome .…”

Debate on the treatment of multiple sclerosis: Experience from an intractable multiple sclerosis case with rebound syndrome after fingolimod cessation

“…Fingolimod rebound syndrome has been reported in a growing number of case series, [3][4][5][6][7][8][9][10][11][12][13][14][15][16] and there were three case series composed of a relatively large number of patients. 3,15,16 In the three studies, the prevalence of fingolimod rebound syndrome ranged from 5 to 53%, although the study whose prevalence was 53% included radiological exacerbation. Rebound syndrome emerged from 3 to 12 weeks after drug cessation, and lymphocyte counts at the rebound ranged from 300 to 2100 (/mm 3 ), elevated from those during the fingolimod treatment.…”