Dimethyl fumarate vs fingolimod following different pretreatments

Diem, Lara; Daponte, Ariadne; Findling, Oliver; Miclea, Andrei; Briner, Myriam; Salmen, Anke; Gold, Ralf; Kilidireas, Constantinos; Chan, Andrew; Evangelopoulos, Maria-Eleftheria; Hoepner, Robert

doi:10.1212/nxi.0000000000000660

Cited by 5 publications

(5 citation statements)

References 8 publications

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“…Fingolimod (Gilenya®) is approved as oral treatment for relapsing-remitting (RR) MS [8,9]. Its efficacy could be demonstrated in different phase III studies [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Fingolimod Therapy in Multiple Sclerosis Leads to the Enrichment of a Subpopulation of Aged NK Cells

et al. 2021

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Fingolimod is an approved oral treatment for relapsing–remitting multiple sclerosis (RRMS) that modulates agonistically the sphingosin-1-phosphate receptor (S1PR), inhibiting thereby the egress of lymphocytes from the lymph nodes. In this interventional prospective clinical phase IV trial, we longitudinally investigated the impact of fingolimod on frequencies of NK cell subpopulations by flow cytometry in 17 RRMS patients at baseline and 1, 3, 6, and 12 months after treatment initiation. Clinical outcome was assessed by the Expanded Disability Status Scale (EDSS) and annualized relapse rates (ARR). Over the study period, median EDSS remained stable from month 3 to month 12, and ARR decreased compared to ARR in the 24 months prior treatment. Treatment was paralleled by an increased frequency of circulating NK cells, due primarily to an increase in CD56dimCD94low mature NK cells, while the CD56bright fraction and CD127+ innate lymphoid cells (ILCs) decreased over time. An unsupervised clustering algorithm further revealed that a particular fraction of NK cells defined by the expression of CD56dimCD16++KIR+/−NKG2A−CD94−CCR7+/−CX3CR1+/−NKG2C−NKG2D+NKp46−DNAM1++CD127+ increased during treatment. This specific phenotype might reflect a status of aged, fully differentiated, and less functional NK cells. Our study confirms that fingolimod treatment affects both NK cells and ILC. In addition, our study suggests that treatment leads to the enrichment of a specific NK cell subset characterized by an aged phenotype. This might limit the anti-microbial and anti-tumour NK cell activity in fingolimod-treated patients.

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“…Fingolimod (Gilenya®) is approved as oral treatment for relapsing-remitting (RR) MS [8,9]. Its efficacy could be demonstrated in different phase III studies [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Fingolimod Therapy in Multiple Sclerosis Leads to the Enrichment of a Subpopulation of Aged NK Cells

et al. 2021

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“…Our results showed a lower discontinuation rate for fingolimod than for dimethyl fumarate (IPTW-weighted HR, 0.60; 95% CI, 0.44-0.84). A retrospective study including 732 patients with RRMS (409 taking dimethyl fumarate and 323 taking fingolimod) showed similar results regarding the discontinuation between dimethyl fumarate and fingolimod (29.3% of patients discontinued dimethyl fumarate vs 20.7% in fingolimod; P = .008). However, the study investigators found that dimethyl fumarate was associated with an increased relapse risk compared with fingolimod, with an HR of 1.9 (95% CI, 1.4-2.6) and a higher relapse risk in patients taking dimethyl fumarate who were pretreated with natalizumab compared with those switching to fingolimod (HR, 4.5; 95% CI, 1.9-10.8).…”

Section: Discussionmentioning

confidence: 79%

“…27,28 Ocrelizumab is a B-cell depleting humanized monoclonal antibody, which has shown a significant efficacy in reducing disease activity and MRI progression compared with interferon beta in 2 phase 3 trials. 29,30 However, evidence has been inconsistent regarding the comparative efficacy of these 3 common DMTs after switching from natalizumab, 22,23,31,32 and a direct comparison between them is lacking.…”

mentioning

confidence: 99%

“…[13][14][15] Fingolimod, a functional antagonist of sphingosine-1phosphate receptors that is effective in reducing relapse rate and improving magnetic resonance imaging (MRI) outcomes in RRMS, 16,17 is commonly used after natalizumab cessation. 10,12,[18][19][20][21] Dimethyl fumarate [22][23][24] and ocrelizumab are 2 other options. 25,26 Dimethyl fumarate is effective in downregulating the proinflammatory responses of T cells, B cells, and myeloid cells.…”

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confidence: 99%

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Comparison Between Dimethyl Fumarate, Fingolimod, and Ocrelizumab After Natalizumab Cessation

et al. 2023

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ImportanceNatalizumab cessation is associated with a risk of rebound disease activity. It is important to identify the optimal switch disease-modifying therapy strategy after natalizumab to limit the risk of severe relapses.ObjectivesTo compare the effectiveness and persistence of dimethyl fumarate, fingolimod, and ocrelizumab among patients with relapsing-remitting multiple sclerosis (RRMS) who discontinued natalizumab.Design, Setting, and ParticipantsIn this observational cohort study, patient data were collected from the MSBase registry between June 15, 2010, and July 6, 2021. The median follow-up was 2.7 years. This was a multicenter study that included patients with RRMS who had used natalizumab for 6 months or longer and then were switched to dimethyl fumarate, fingolimod, or ocrelizumab within 3 months after natalizumab discontinuation. Patients without baseline data were excluded from the analysis. Data were analyzed from May 24, 2022, to January 9, 2023.ExposuresDimethyl fumarate, fingolimod, and ocrelizumab.Main Outcomes and MeasuresPrimary outcomes were annualized relapse rate (ARR) and time to first relapse. Secondary outcomes were confirmed disability accumulation, disability improvement, and subsequent treatment discontinuation, with the comparisons for the first 2 limited to fingolimod and ocrelizumab due to the small number of patients taking dimethyl fumarate. The associations were analyzed after balancing covariates using an inverse probability of treatment weighting method.ResultsAmong 66 840 patients with RRMS, 1744 had used natalizumab for 6 months or longer and were switched to dimethyl fumarate, fingolimod, or ocrelizumab within 3 months of natalizumab discontinuation. After excluding 358 patients without baseline data, a total of 1386 patients (mean [SD] age, 41.3 [10.6] years; 990 female [71%]) switched to dimethyl fumarate (138 [9.9%]), fingolimod (823 [59.4%]), or ocrelizumab (425 [30.7%]) after natalizumab. The ARR for each medication was as follows: ocrelizumab, 0.06 (95% CI, 0.04-0.08); fingolimod, 0.26 (95% CI, 0.12-0.48); and dimethyl fumarate, 0.27 (95% CI, 0.12-0.56). The ARR ratio of fingolimod to ocrelizumab was 4.33 (95% CI, 3.12-6.01) and of dimethyl fumarate to ocrelizumab was 4.50 (95% CI, 2.89-7.03). Compared with ocrelizumab, the hazard ratio (HR) of time to first relapse was 4.02 (95% CI, 2.83-5.70) for fingolimod and 3.70 (95% CI, 2.35-5.84) for dimethyl fumarate. The HR of treatment discontinuation was 2.57 (95% CI, 1.74-3.80) for fingolimod and 4.26 (95% CI, 2.65-6.84) for dimethyl fumarate. Fingolimod use was associated with a 49% higher risk for disability accumulation compared with ocrelizumab. There was no significant difference in disability improvement rates between fingolimod and ocrelizumab.Conclusion and RelevanceStudy results show that among patients with RRMS who switched from natalizumab to dimethyl fumarate, fingolimod, or ocrelizumab, ocrelizumab use was associated with the lowest ARR and discontinuation rates, and the longest time to first relapse.

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“…Only 6/33 (18%) reached protective antibody levels after two mRNA vaccinations. Further research is needed to identify strategies allowing vaccination under FTY treatment without the risk of a disease reactivation due to a prolonged drug holiday, which is known to occur in patients after stopping FTY [5]. As a limitation, the retrospective nature and small cohort size of our study have to be mentioned.…”

Section: Discussionmentioning

confidence: 97%

"Comparable Efficacy of SARS-CoV-2 mRNA Vaccines (BNT162b2 and mRNA-1273) in Fingolimod-Treated Patients with Multiple Sclerosis"

Hammer

2023

BJSTR

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Dimethyl fumarate vs fingolimod following different pretreatments

Cited by 5 publications

References 8 publications

Fingolimod Therapy in Multiple Sclerosis Leads to the Enrichment of a Subpopulation of Aged NK Cells

Fingolimod Therapy in Multiple Sclerosis Leads to the Enrichment of a Subpopulation of Aged NK Cells

Comparison Between Dimethyl Fumarate, Fingolimod, and Ocrelizumab After Natalizumab Cessation

"Comparable Efficacy of SARS-CoV-2 mRNA Vaccines (BNT162b2 and mRNA-1273) in Fingolimod-Treated Patients with Multiple Sclerosis"

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