Three-Year Effectiveness of Dimethyl Fumarate in Multiple Sclerosis: A Prospective Multicenter Real-World Study

Fuente, Belén Pilo de la; Sabin, Julia; Galán, Victoria; Thuissard, Israel; Maza, Susana Sainz de la; Costa‐Frossard, Lucienne; Gómez-Moreno, Mayra; Díaz-Díaz, Judit; Oreja‐Guevara, Celia; Lozano-Ros, Alberto; García-Domínguez, J M; Borrego, Laura; Ayuso, Lucía; Castro, Andy; Sánchez, Pedro; Meca-Lallana, Virginia; Muñoz, Carmen; Casanova, Ignacio; Silanes, Carlos López de; Martin, H.; Rodriguez-García, Elena; Andreu‐Vázquez, Cristina; Blasco, R. Serna; García-Merino, J.A.; Aladro, Yolanda

doi:10.1007/s40263-020-00775-9

Cited by 6 publications

(6 citation statements)

References 26 publications

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“…The analysis of NEDA-3 after more than 2 years from the start of DMT has been reported in relatively few MS studies, such as the 5-year follow-up from CARE-MS I and CARE-MS II with alemtuzumab 14 , 15 and the 3-year follow-up with dimethyl fumarate. 16 The relevance of looking at NEDA in Years 3 and 4 after starting treatment with cladribine tablets is that patients would not normally receive any DMTs during this time, according to the recommended dosing. 8 It is expected that patients would be regularly monitored by their physicians during Years 3 and 4, and many might judge treatment success by the achievement of NEDA or a reduction in disease activity compared to a period before cladribine tablets were commenced.…”

Section: Discussionmentioning

confidence: 99%

Durability of no evidence of disease activity-3 (NEDA-3) in patients receiving cladribine tablets: The CLARITY extension study

Giovannoni

Issard³

et al. 2021

Mult Scler

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Background: No evidence of disease activity (NEDA-3) is a patient-centric outcome increasingly used as the goal of multiple sclerosis treatment. Objective: Determine treatment durability of cladribine tablets beyond 2 years considering the variable bridging interval of 0.1–116.0 weeks between CLARITY and CLARITY Extension. Methods: Between CLARITY and CLARITY Extension, patients transitioned from cladribine tablets 3.5 mg/kg to placebo (CP3.5 group, n = 98) or continued further treatment with cladribine tablets 3.5 mg/kg (CC7.0 group, n = 186). Treatment assignment was randomized and blinded in both CLARITY and CLARITY Extension. Results: The 2-year NEDA-3 in CLARITY Extension (encompassing both years of CLARITY Extension) was 29.6% in the CP3.5 group and 32.8% in the CC7.0 group. There was no evidence that treatment effect differed with varying bridging intervals. For patients in the CP3.5 group with a bridging interval of ⩽48 weeks, 1 year NEDA-3 (the first year of CLARITY Extension) was 44.4% (28/63) compared with 31.4% (11/35) in patients with a bridging interval of >48 weeks. Conclusion: Treatment with cladribine tablets in CLARITY, followed by either placebo or cladribine tablets in CLARITY Extension, produced sustained benefits for NEDA-3 and its constituent elements for a follow up period up to 6 years from CLARITY baseline.

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Section: Discussionmentioning

confidence: 99%

Durability of no evidence of disease activity-3 (NEDA-3) in patients receiving cladribine tablets: The CLARITY extension study

Giovannoni

Issard³

et al. 2021

Mult Scler

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“…Similarly, we found a higher NEDA3 status of those described in the integrated analysis of the phase III DEFINE and CONFIRM studies ( 22 ). Finally, other studies of real-world setting found a higher baseline EDSS, a larger number of T1Gd+ lesions, and a switch because of inefficacy (vs. adverse events) as the principal risk factors for losing NEDA-3 status ( 23 ).…”

Section: Discussionmentioning

confidence: 90%

The Dimethyl Fumarate Experience: A Handy Drug With Broad Clinical Utility

et al. 2021

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Objectives: The aim of this study was to characterize multiple sclerosis (MS) patients exposed to dimethyl fumarate (DMF) and to evaluate the predictors of therapeutic response. In addition, the study offers a picture of how DMF use has changed over the past few years in naive or switcher patients.Methods: In this observational monocentric study, we examined the prescription flow of DMF in MS patients categorized as naive or switchers (for safety/tolerability, ineffectiveness, and de-escalation strategy) from 2015 to 2019. Clinical and magnetic resonance imaging data of DMF-treated patients were analyzed, and NEDA-3 status at 24 months was evaluated by the three assessment components (absence of clinical relapses, no Expanded Disability Status Scale progression, no radiological activity). Determinants of therapeutic response were also evaluated using regression analysis.Results: The sample included 595 MS patients exposed to DMF categorized as naive (158; 26.5%) and switchers for reasons of safety/tolerability (198; 33.3%), inefficacy (175; 29.4%), and de-escalation strategy (64; 10.8%). A 15% increase in DMF use in naive and horizontal shift groups was observed in the last 3 years of observation, whereas there was a drop, with prescription passed from ~20% to <5%, as an exit strategy from second-line therapies. NEDA-3 status was calculated for 340 patients after 24 months of DMF treatment and achieved in 188 (55.3%) of these. Analyzing the predictors of DMF response, we observed that lower annualized relapse rate (ARR) in 2 years pretreatment [hazard ratio (HR) = 0.49, p = 0.001] and being naive patients (HR = 1.38, p = 0.035) were associated with achievement of NEDA-3. Analogously, ARR in 2 years pretreatment affected the NEDA-3 achievement at 24 months in patients of the de-escalation group (HR = 0.07, p = 0.041), also indicating an effect related to the DMF initiation within 3 months (HR = 1.24, p = 0.029).Conclusion: Our findings confirm DMF as a handy drug with broad clinical utility, with greater benefits for naive patients and horizontal switchers. Additionally, an increase in the flow of DMF prescriptions in these two groups of patients was also observed in our cohort.

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“…Regarding the assessment of disease activity, this study lacks the evaluation of gadolinium-enhancing, lesions which is not included in our clinical practice according to the most recent MAGNIMS-CMSC-NAIMS consensus recommendations on the use of MRI in patients with MS. 39 This lack does not permit an adequate comparison with other real-life cohorts. 30,40 Notably, evidences from comparative studies suggested a higher rate of cortical GM volume change in patients treated with DMF; 13 its capability to reduce brain atrophy loss when compared with other treatments, has been debated. 14,41 Although in line with recent studies suggesting a reduction of neurodegenerative biomarkers in the CSF of patients treated with DMF, 42 the monocenter, not comparative, and relative short-term design of this study prevent a generalization of our results: future multicenter studies with longer follow-up are required to confirm the real neuroprotective effect of DMF.…”

Section: Discussionmentioning

confidence: 99%

Two years’ effect of dimethyl fumarate on focal and diffuse gray matter pathology in multiple sclerosis

Marastoni

Crescenzo²,

Pisani

et al. 2022

Mult Scler

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Background: Data on the effect of dimethyl fumarate (DMF) on focal and diffuse gray matter (GM) damage, a relevant pathological substrate of multiple sclerosis (MS)-related disability are lacking. Objective: To evaluate the DMF effect on cortical lesions (CLs) accumulation and global and regional GM atrophy in subjects with relapsing–remitting MS. Methods: A total of 148 patients (mean age 38.1 ± 9.7 years) treated with DMF ended a 2-year longitudinal study. All underwent regular Expanded Disability Status Scale (EDSS assessment), and at least two 3T-magnetic resonance imaging (MRI) at 3 and 24 months after DMF initiation. CLs and changes in global and regional atrophy of several brain regions were compared with 47 untreated age and sex-matched patients. Results: DMF-treated patients showed lower CLs accumulation (median 0[0–3] vs 2[0–7], p < 0.001) with respect to controls. Global cortical thickness ( p < 0.001) and regional thickness and volume were lower in treated group (cerebellum, hippocampus, caudate, and putamen: p < 0.001; thalamus p = 0.03). Lower relapse rate (14% vs 40%, p < 0.001), EDSS change (0.2 ± 0.4 vs 0.4 ± 0.9, p < 0.001), and new WM lesions (median 0[0–5] vs 2[0–6], p < 0.001) were reported. No severe adverse drug reactions occurred. Conclusions: Beyond the well-known effect on disease activity, these results provide evidence of the effect of DMF through reduced progression of focal and diffuse GM damage.

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Three-Year Effectiveness of Dimethyl Fumarate in Multiple Sclerosis: A Prospective Multicenter Real-World Study

Cited by 6 publications

References 26 publications

Durability of no evidence of disease activity-3 (NEDA-3) in patients receiving cladribine tablets: The CLARITY extension study

Durability of no evidence of disease activity-3 (NEDA-3) in patients receiving cladribine tablets: The CLARITY extension study

The Dimethyl Fumarate Experience: A Handy Drug With Broad Clinical Utility

Two years’ effect of dimethyl fumarate on focal and diffuse gray matter pathology in multiple sclerosis

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