Tolerability and safety of dimethyl fumarate in relapsing multiple sclerosis: a prospective observational multicenter study in a real-life Spanish population

Sabin, Julia; Urtiaga, S; Pilo, Belén; Thuissard, Israel; Galán, Victoria; Maza, Susana Sainz de la; Costa‐Frossard, Lucienne; Gómez-Moreno, Mayra; Díaz-Díaz, Judit; Oreja‐Guevara, Celia; Martínez-Ginés, María Luisa; Lozano, Alberto Arribas; Borrega, Laura; Ayuso, Lucía; Castro, Andy; Sánchez, Pedro; Meca-Lallana, Virginia; Muñoz, Carmen; Casanova, Ignacio; Silanes, Carlos López de; Martin, H.; Rodriguez-García, Elena; Moreno, Irene; García-Merino, J.A.; Aladro, Yolanda

doi:10.1007/s00415-020-09848-7

Cited by 23 publications

(16 citation statements)

References 17 publications

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“…A recent paper from Sabin et al found a 30% incidence rate for lymphopenia with 6% of grade III lymphopenia [26]. Their cohort was comparable to ours in terms of DMF exposure duration (3 years), naïve/switchers ratio (near 30% of naïve patients) and mean age (near 40 years).…”

Section: Discussionsupporting

confidence: 83%

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Predictors of lymphocyte count recovery after dimethyl fumarate-induced lymphopenia in people with multiple sclerosis

et al. 2021

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Background Dimethyl fumarate (DMF) is an oral drug approved for Relapsing Multiple Sclerosis (RMS) patients. Grade III lymphopenia is reported in 5–10% DMF-treated patients. Data on lymphocyte count (ALC) recovery after DMF withdrawal following prolonged lymphopenia are still scarce. Objectives To characterize ALC recovery and to identify predictors of slower recovery after DMF interruption. Methods Multicenter data from RMS patients who started DMF and developed lymphopenia during treatment were collected. In patients with grade II–III lymphopenia, ALCs were evaluated from DMF withdrawal until reaching lymphocyte counts > 800/mm3. Results Among 1034 patients who started DMF, we found 198 (19.1%) patients with lymphopenia and 65 patients (6.3%) who discontinued DMF due to persistent grade II–III lymphopenia. Complete data were available for 51 patients. All patients recovered to ALC > 800 cells/mm3 with a median time of 3.4 months. Lower ALCs at DMF suspension (HR 0.98; p = 0.005), longer disease duration (HR 1.29; p = 0.014) and prior exposure to MS treatments (HR 0.03; p = 0.025) were found predictive of delayed ALC recovery. Conclusion ALC recovery after DMF withdrawal is usually rapid, nevertheless it may require longer time in patients with lower ALC count at DMF interruption, longer disease duration and previous exposure to MS treatments, potentially leading to delayed initiation of a new therapy.

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Section: Discussionsupporting

confidence: 83%

“…Our study shows a comparable rate of grade III lymphopenia while we found a lower incidence of lymphopenia including all grades. Difference among laboratories in the reference values defining lower normal lymphocyte limit may account for variability in grade I lymphopenia diagnosis [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Predictors of lymphocyte count recovery after dimethyl fumarate-induced lymphopenia in people with multiple sclerosis

et al. 2021

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“…1,2,17 We observed frequency of lymphopenia more in alignment with a recent multicenter registry study in Spain which reported sustained lymphopenia (ALN <1000/ll) in 30% of patients. An association of lymphopenia with older age (OR 1.04, p < 0.001) and higher EDSS (OR 1.10, p ¼ 0.035) 18 was reported in this cohort. The DMF group in our study was older (mean age 56.5 versus 37.8-38.9 years) 1,2,15,16 and had on average a higher EDSS (5.3 versus 2.6-2.4) 1,2 than the subjects reported in the clinical trials and real-world studies.…”

Section: Discussionsupporting

confidence: 59%

Effectiveness and safety of dimethyl fumarate in progressive multiple sclerosis

Ferreira

Liu

Healy

et al. 2021

Multiple Sclerosis Journal - Experimental, Translational and Cl

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Background There is limited data analyzing the safety and effectiveness of dimethyl fumarate (DMF) in the progressive multiple sclerosis (PMS) population. Objective To analyze the safety and effectiveness of DMF in patients with PMS. Methods We used Cox proportional hazards models to compare the time to confirmed worsening and improvement on the Expanded Disability Status Scale (EDSS) and timed 25-foot walk (T25FW) between patients treated with DMF and glatiramer acetate (GA) for at least one year. Results We included 46 patients treated with DMF and 42 patients treated with GA. The safety and tolerability of GA and DMF were consistent with established profiles. There was no difference in confirmed EDSS progression. A trend towards reduced T25FW was seen in the DMF compared to GA after adjustment (HR = 0.86; 95% CI:0.37, 1.98; p = 0.72 and HR = 0.60; 95% CI:0.27, 1.34; p = 0.21, respectively). Conclusion Dimethyl fumarate showed a trend towards reduction in T25FW but no evidence of clinically significant impact on EDSS. The small sample precluded definitive determination.

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“…On the other hand, DMF, by reducing the lymphocyte count in a subset of patient may theoretically increase their risk of COVID-19. In a post-marketing prospective study, 4-6% out of 886 MS patients exposed to DMT developed grade III lymphopenia [18]. Nonetheless, serious infections are rarely reported in DMF-treated patients and occurred in <5% of patients, with no association between lymphopenia and increased incidence of infection [19].…”

mentioning

confidence: 99%

COVID‐19 in dimethyl fumarate‐treated patients with multiple sclerosis

Mantero¹,

Abate

Basilico³

et al. 2020

J Neurol

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Despite a few initial reports [1-5], the risk and course of COVID-19 in patients with multiple sclerosis (MS) is still unclear. Although neurological disability and comorbid conditions may be important factors, the role played by immune-based disease-modifying therapies (DMTs) in patients with MS has attracted the most attention in this regard [6]. Patients with MS have a generally increased risk of infections [7], particularly those with more severe disability or significant co-morbidities, with evidence for a role for infections in triggering MS relapses or worsening preexisting MS symptoms [8]. MS patients are generally twice as likely to be hospitalized for infections than the general population [9]. Recently, Maghzi et al. [10] reported in this journal a case series of five teriflunomide-treated MS patients who developed COVID-19 infection and continued their therapy with a self-limiting infection and without any relapse. The authors hypothesized that the immune-biologic mechanisms pertaining to teriflunomide have a potential role in favoring a COVID-19-positive outcome.

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Tolerability and safety of dimethyl fumarate in relapsing multiple sclerosis: a prospective observational multicenter study in a real-life Spanish population

Cited by 23 publications

References 17 publications

Predictors of lymphocyte count recovery after dimethyl fumarate-induced lymphopenia in people with multiple sclerosis

Predictors of lymphocyte count recovery after dimethyl fumarate-induced lymphopenia in people with multiple sclerosis

Effectiveness and safety of dimethyl fumarate in progressive multiple sclerosis

COVID‐19 in dimethyl fumarate‐treated patients with multiple sclerosis

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