Discontinuation and comparative effectiveness of dimethyl fumarate and fingolimod in 2 centers

BackgroundDimethyl fumarate (DMF) and fingolimod (FTY) are approved oral disease-modifying therapies for relapsing multiple sclerosis (MS). Observational studies are valuable when randomized clinical trials cannot be done due to ethical or practical reasons. Two-site studies allow investigators to further ascertain external validity of previously examined treatment effect differences. Limited head-to-head 2-site studies exist comparing DMF and FTY.MethodsPatients prescribed DMF (n = 737) and FTY (n = 535) from 2 academic multiple sclerosis (MS) centers (Cleveland Clinic and University of Colorado) were identified. Discontinuation and disease activity endpoints were assessed using propensity score (PS) weighting. Covariates used in the PS model included demographics and clinical and MRI characteristics.ResultsPS weighting demonstrated excellent covariate balance. Discontinuation was more common in DMF (44.2%) compared to FTY (34.8%) over 24 months (odds ratio [OR] 1.55, 95% confidence interval [CI] 1.21–1.99, p < 0.001). The leading cause for discontinuation was intolerability for both DMF (56.1% of DMF discontinuations) and FTY (46.2% of FTY discontinuations) (OR 1.65, 95% CI 1.21–2.25, p = 0.002). The proportion of patients with clinical relapses was low for both medications (DMF, 15.1%; FTY, 13.1%). There was no difference in the proportion of patients with relapses (OR 1.27, 95% CI 0.90–1.80, p = 0.174), gadolinium-enhancing lesions (OR 1.42, 95% CI 0.92–2.20, p = 0.114), or new T2 lesions on brain MRI (OR 1.13, 95% CI 0.83–1.55, p = 0.433).ConclusionsThis combined analysis suggests DMF and FTY have similar effectiveness in a large, 2-site clinical population over 24 months. Discontinuation of both DMTs was common and occurred more frequently with DMF, largely driven by intolerability.

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Comparative effectiveness of teriflunomide vs dimethyl fumarate in multiple sclerosis

Neurology ◽

10.1212/wnl.0000000000007938 ◽

2019 ◽

Vol 93 (7) ◽

pp. e635-e646 ◽

Cited By ~ 10

Author(s):

David-Axel Laplaud ◽

Romain Casey ◽

Laetitia Barbin ◽

Marc Debouverie ◽

Jérôme De Sèze ◽

...

Keyword(s):

Multiple Sclerosis ◽

Propensity Scores ◽

Brain Mri ◽

Clinical Effectiveness ◽

Dimethyl Fumarate ◽

Treatment Discontinuation ◽

Treatment Withdrawal ◽

Class Iii ◽

Intention To Treat ◽

T2 Lesions

ObjectiveIn this study, we compared the effectiveness of teriflunomide (TRF) and dimethyl fumarate (DMF) on both clinical and MRI outcomes in patients followed prospectively in the Observatoire Français de la Sclérose en Plaques.MethodsA total of 1,770 patients with relapsing-remitting multiple sclerosis (RRMS) (713 on TRF and 1,057 on DMF) with an available baseline brain MRI were included in intention to treat. The 1- and 2-year postinitiation outcomes were relapses, increase of T2 lesions, increase in Expanded Disability Status Scale score, and reason for treatment discontinuation. Propensity scores (inverse probability weighting) and logistic regressions were estimated.ResultsThe confounder-adjusted proportions of patients were similar in TRF- compared to DMF-treated patients for relapses and disability progression after 1 and 2 years. However, the adjusted proportion of patients with at least one new T2 lesion after 2 years was lower in DMF compared to TRF (60.8% vs 72.2%, odds ratio [OR] 0.60, p < 0.001). Analyses of reasons for treatment withdrawal showed that lack of effectiveness was reported for 8.5% of DMF-treated patients vs 14.5% of TRF-treated patients (OR 0.54, p < 0.001), while adverse events accounted for 16% of TRF-treated patients and 21% of DMF-treated patients after 2 years (OR 1.39, p < 0.001).ConclusionsAfter 2 years of treatment, we found similar effectiveness of DMF and TRF in terms of clinical outcomes, but with better MRI-based outcomes for DMF-treated patients, resulting in a lower rate of treatment discontinuation due to lack of effectiveness.Classification of evidenceThis study provides Class III evidence that for patients with RRMS, TRF and DMF have similar clinical effectiveness after 2 years of treatment.

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Slowly expanding/evolving lesions as a magnetic resonance imaging marker of chronic active multiple sclerosis lesions

Multiple Sclerosis Journal ◽

10.1177/1352458518814117 ◽

2018 ◽

Vol 25 (14) ◽

pp. 1915-1925 ◽

Cited By ~ 24

Author(s):

Colm Elliott ◽

Jerry S Wolinsky ◽

Stephen L Hauser ◽

Ludwig Kappos ◽

Frederik Barkhof ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Multiple Sclerosis ◽

Magnetic Resonance ◽

Brain Mri ◽

Brain Magnetic Resonance Imaging ◽

Tissue Loss ◽

Jacobian Determinant ◽

Resonance Imaging ◽

T2 Lesions ◽

Magnetic Resonance Imaging Mri

Background: Chronic lesion activity driven by smoldering inflammation is a pathological hallmark of progressive forms of multiple sclerosis (MS). Objective: To develop a method for automatic detection of slowly expanding/evolving lesions (SELs) on conventional brain magnetic resonance imaging (MRI) and characterize such SELs in primary progressive MS (PPMS) and relapsing MS (RMS) populations. Methods: We defined SELs as contiguous regions of existing T2 lesions showing local expansion assessed by the Jacobian determinant of the deformation between reference and follow-up scans. SEL candidates were assigned a heuristic score based on concentricity and constancy of change in T2- and T1-weighted MRIs. SELs were examined in 1334 RMS patients and 555 PPMS patients. Results: Compared with RMS patients, PPMS patients had higher numbers of SELs ( p = 0.002) and higher T2 volumes of SELs ( p < 0.001). SELs were devoid of gadolinium enhancement. Compared with areas of T2 lesions not classified as SEL, SELs had significantly lower T1 intensity at baseline and larger decrease in T1 intensity over time. Conclusion: We suggest that SELs reflect chronic tissue loss in the absence of ongoing acute inflammation. SELs may represent a conventional brain MRI correlate of chronic active MS lesions and a candidate biomarker for smoldering inflammation in MS.

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060 Association of brain volume loss and neda outcomes in patients with relapsing multiple sclerosis in the opera i and opera ii studies (ENCORE)

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2018-anzan.59 ◽

2018 ◽

Vol 89 (6) ◽

pp. A25.1-A25

Author(s):

Anthony Traboulsee ◽

Douglas Arnold ◽

Eric C Klawiter ◽

Eva Havrdova ◽

Damian Fiore ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Activity ◽

Brain Tissue ◽

Repeated Measures ◽

Brain Volume ◽

Brain Mri ◽

Treatment Goal ◽

Volume Loss ◽

T2 Lesions ◽

Brain Volume Loss

IntroductionBrain volume loss (BVL) occurs in multiple sclerosis (MS) patients, reflecting irreversible tissue damage. No evidence of disease activity (NEDA), a composite measure assessing absence of clinical and magnetic resonance imaging (MRI) disease activity has emerged as important treatment goal in MS and may be associated with preservation of brain tissue and BVL prevention.MethodsPatients in OPERA-I/II (NCT01247324/NCT01412333) received 600 mg ocrelizumab (intravenous) very 24 weeks or 44 µg subcutaneous interferon beta-1a (IFNβ-1a) 3x-weekly for 96 weeks. Brain MRI assessments were completed at baseline and 24/48/96 Weeks. Brain volume normalised for head size was measured using SIENAX software. Percent change in whole brain volume (WBV) was determined using SIENA software, changes in cortical grey (GMV) and white (WMV) matter volumes were measured using validated, locally developed Jacobian integrator atrophy software. NEDA was defined as absence of relapses, 12-week confirmed disability progression, T1 Gd–enhancing lesions and new and/or enlarging T2-lesions. Changes from baseline in brain volume were examined in NEDA patients and those with evidence of disease activity (EDA), using the mixed-effects model for repeated measures method.ResultsThe analysis included 1520 patients (ocrelizumab-761; IFNβ-1a-759). Over 96 weeks, 569 (37%) patients [ocrelizumab-363 (48%); IFNβ-1a-206(27%); p<0.001] had NEDA. Compared with EDA patients, NEDA patients had significantly less WBV loss from baseline (30%-reduction; p<0.001). In the NEDA group, ocrelizumab patients had significantly less WBV loss (32%-reduction; p<0.001), WMV loss (34%-reduction; p=0.044) and GMV loss (30%-reduction; p<0.001) from baseline than IFNβ-1a patients. In the EDA group, ocrelizumab patients had significantly less WBV loss (11%-reduction; p=0.047) and GMV loss (21%-reduction; p<0.001) but not WMV loss (1.03%-increase; p=0.90) from baseline than IFNβ-1a patients.ConclusionThese findings highlight the importance of NEDA as treatment goal with respect to brain tissue preservation regardless of treatment choice. Ocrelizumab may confer additional benefits in NEDA patients NEDA beyond what is observed with IFNβ-1a.

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005 Filling in the gaps: precision MRI reporting in multiple sclerosis clinical practice

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2018-anzan.5 ◽

2018 ◽

Vol 89 (6) ◽

pp. A3.2-A4

Author(s):

Heidi Beadnall ◽

Yael Barnett ◽

Linda Ly ◽

Chenyu Wang ◽

Thibo Billiet ◽

...

Keyword(s):

Multiple Sclerosis ◽

Quantitative Data ◽

Clinical Decision Making ◽

Brain Mri ◽

Clinical Decision ◽

Quantitative Information ◽

Quantitative Mri ◽

Brain Volumes ◽

T2 Lesions ◽

Radiology Reports

IntroductionClinical multiple sclerosis (MS) magnetic resonance imaging (MRI) brain reports provide important information to neurologists. The quantitative data reported varies between centres and radiologists. Structured MRI reporting and formal quantitative MRI (QMRI) analysis may assist clinicians with patient management. The objective is to compare quantitative data derived from standard clinical reports, structured neuroradiologist reviews, local QMRI analyses and fully-automated MSmetrix QMRI analyses, in a longitudinal clinical MS cohort.MethodsClinical brain MRI scans separated by one-year minimum, from the same patient on the same scanner, were evaluated. Quantitative information was extracted from the clinical reports and structured neuroradiologist reviews. MRI scan-pairs were analysed locally by imaging-analysts and centrally by MSmetrix.Results50 MS patients, baseline age 39.02 (9.06) years, disease duration 9.11 (6.88) years and Expanded Disability Status Scale score 1.91 (1.62), were included. Compared to clinical reports, structured neuroradiologist reviews provided increased semi-/quantitative data; baseline T2 and T1 lesion burden (50% vs 100%; 2% vs 100%), baseline brain volume-loss (BVL; 72% vs 100%), new T1 lesions (0% vs 100%), regional brain atrophy (BA; 20% vs 100%). Lesion and brain volumes were not provided in radiology reports/reviews. Comparison of local and central QMRI revealed moderate-strong Pearson correlations for most metrics; Intra-class correlations varied more widely. Statistical consistency existed across all methods in detecting new T2 lesions. Radiologist-identified baseline BVL was associated with lower quantitatively-measured brain volumes. Local QMRI longitudinal BA rates >0.4% and >0.8%, were 48% and 26% respectively. Neuroradiologist review identified BA in 12%.ConclusionStructured neuroradiology review provided additional quantitative information over standard clinical reports. Quantitative data measured using local and MSmetrix pipelines were generally well associated but are not interchangeable. Longitudinal whole brain and regional atrophy is not reliably identified by radiologists and QMRI analysis provides a clear advantage in this regard. Structured reporting, and formal QMRI analysis, provide additional quantitative MRI data that may assist clinical decision-making in MS.

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The efficacy and safety of oral disease-modifying therapies for relapsing-remitting multiple sclerosis: A systematic review

Current Journal of Neurology ◽

10.18502/cjn.v19i3.5427 ◽

2021 ◽

Author(s):

Rahil Sadat Shahtaheri ◽

Shekoufeh Nikfar ◽

Elahe Khorasani ◽

Mansoureh Sabbagh-Baniazad ◽

Zahra Goudarzi ◽

...

Keyword(s):

Multiple Sclerosis ◽

Systematic Review ◽

Side Effects ◽

Dimethyl Fumarate ◽

Oral Disease ◽

Diabetic Patients ◽

Mri Findings ◽

Disease Modifying Drugs ◽

Relapsing Remitting ◽

Disease Modifying

Background: Although widely used, first-line injectable medicines for the treatment of multiple sclerosis (MS) remain an issue of efficacy and adherence. Recently, new oral medications for MS have contributed to dramatic improvements in MS treatment. This study aims to evaluate the safety and efficacy of oral disease-modifying drugs (DMDs) used in relapsing-remitting MS (RRMS). Methods: A systematic review was conducted on related databases including PubMed, Scopus, Cochrane, and Web of Science up to April 2020. The screening of the studies and their quality assessment was carried out independently by the two authors. Results: Three studies fulfilled the predefined criteria of inclusion. One of them compared teriflonomide with subcutaneous interferon beta-1a (IFN β-1a), another compared oral fingolimod with intramuscular (IM) IFN β-1b, and the third article compared oral fingolimod with IM IFN β-1a. No eligible study was found for dimethyl fumarate (DMF). The results indicated that while the efficacy of fingolimod was more than IFN β (IM β-1a and β-1b), teriflunomide 7 mg had less efficacy than subcutaneous IFN β-1a. Regarding safety, the results indicated that the proportion of diabetic patients with adverse events (AEs) in the fingolimod group was higher than in the IFN β-1b group and the overall occurrence of AEs was similar between teriflunomide and IFN β-1a groups. Conclusion: There is evidence for the effectiveness of fingolimod in reducing annualized relapse rates (ARRs) and improving magnetic resonance imaging (MRI) findings, but the evidence does not support the effectiveness of teriflunomide and further studies are required to determine its efficacy. Also, fingolimod is associated with more side effects than IFN β-1b, but there is no evidence to suggest any difference in side effects between teriflunomide and IFN β-1a.

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Delayed-Release Dimethyl Fumarate Safety and Efficacy in Pediatric Patients With Relapsing-Remitting Multiple Sclerosis

Frontiers in Neurology ◽

10.3389/fneur.2020.606418 ◽

2021 ◽

Vol 11 ◽

Author(s):

Raed Alroughani ◽

Peter Huppke ◽

Maria Mazurkiewicz-Beldzinska ◽

Astrid Blaschek ◽

Martin Valis ◽

...

Keyword(s):

Multiple Sclerosis ◽

Pediatric Patients ◽

Dimethyl Fumarate ◽

Relative Reduction ◽

Hyperintense Lesion ◽

Safety And Efficacy ◽

Delayed Release ◽

T2 Lesions ◽

Relapsing Remitting Multiple Sclerosis

Background: Pediatric multiple sclerosis (MS) is rare: only 1.5–5% of MS cases are diagnosed before 18 years of age, and data on disease-modifying therapies (DMTs) for pediatric MS are limited. The CONNECTED study assessed the long-term safety and efficacy of treatment with delayed-release dimethyl fumarate (DMF), an oral MS DMT, in pediatric patients with MS.Methods: CONNECTED is the 96-week extension to FOCUS, a 24-week phase 2 study of patients aged 13–17 years; participants received DMF 240 mg twice daily. Endpoints included (primary) incidence of adverse events (AEs), serious AEs, and DMF discontinuations due to an AE, and (secondary) T2 hyperintense lesion incidence by magnetic resonance imaging and annualized relapse rate (ARR).Results: Twenty participants [median (range) age, 17 (14–18) years; 65% female] who completed FOCUS enrolled into CONNECTED; 17 (85%) completed CONNECTED. Eighteen participants (90%) experienced AEs: the most frequent was flushing (25%). None experienced infections or fever related to low lymphocyte counts. Three participants experienced four serious AEs; none led to DMF discontinuation. Twelve of 17 participants (71%) had no new/newly enlarged T2 lesions from weeks 16–24, two (12%) had one, and one each (6%) had two, three, or five or more lesions [median (range), 0 (0–6)]. Over the full 120-week treatment period, ARR was 0.2, an 84.5% relative reduction (n = 20; 95% confidence interval: 66.8–92.8; p < 0.0001) vs. the year before DMF initiation.Conclusions: The long-term safety and efficacy observed in CONNECTED was consistent with adults, suggesting pediatric and adolescent patients with MS might benefit from DMF treatment.

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Ozanimod for Treatment of Relapsing-Remitting Multiple Sclerosis in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Frontiers in Pharmacology ◽

10.3389/fphar.2020.589146 ◽

2020 ◽

Vol 11 ◽

Author(s):

Yue Sun ◽

Yanbo Yang ◽

Zilan Wang ◽

Fan Jiang ◽

Zhouqing Chen ◽

...

Keyword(s):

Multiple Sclerosis ◽

Clinical Trials ◽

Adverse Events ◽

Treatment Period ◽

Relapse Rate ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

T2 Lesions ◽

Relapsing Remitting ◽

Annualized Relapse Rate

Background: Ozanimod has been approved for use in the treatment of relapsing forms of multiple sclerosis by the United States FDA. As a novel, orally available sphingosine 1-phosphate receptor modulator, ozanimod selectively binds to S1P1 and S1P5 receptor with high affinity, minimizing safety concerns caused by S1P3 receptor activation.Methods: e systematically searched PUBMED, EMBASE database, and Cochrane Library database to identify randomized controlled trials (RCTs) from inception to June 28, 2020. Trials were considered eligible if they 1) were randomized clinical trials (RCTs); 2) enrolled adult participants diagnosed with Relapsing-remitting MS; 3) compared ozanimod with placebo or any other approved DMDs that evaluated in phase III or phase II clinical trials; 4) enrolled over 100 participants; 5) provided any available information for predefined primary or secondary outcomes.Results: 2917 participants from three high-quality, multi-centered randomized clinical trials were pooled in our analysis. We found that using ozanimod was significantly associated with the reduction of the annualized relapse rate during the treatment period (RR, −0.10 [95% CI, −0.15, −0.06]). Also, the decreased number of gadolinium-enhancing lesions at the end of the trial was relative to the treatment of ozanimod (ozanimod, 0.29; control, 0.65; RR, −0.20 [95% CI, −0.34, −0.06]). Compared with patients in the control group, the number of new or enlarging T2 lesions over the treatment period decreased in patients treated with ozanimod (ozanimod, 1.82; control, 3.55; RR, −1.12 [95% CI, −1.52, −0.71]). As to the safety endpoints, patients in the ozanimod group reported a lower rate of adverse events (ozanimod, 66.03%; control, 77.07%; RR, 0.64 [95% CI, 0.43, 0.95]). Similar incidence of infection-related TEAEs was found across treatment groups (nasopharyngitis: ozanimod, 11.19%; control, 9.83%; RR, 1.10 [95% CI, 0.77–1.57]; urinary-tract infection: ozanimod, 3.81%; control, 2.97%; RR, 1.29 [95% CI, 0.83–2.00]). No case of macular edema was noted as well as second-degree, type 2, or third-degree atrioventricular block. As for the subgroup analysis, compared with 0.5 mg ozanimod, 1 mg ozanimod is related with a significant reduction of the annualized relapse rate during the treatment period (1 mg ozanimod, 0.18; 0.5 mg ozanimod, 0.24; RR, 0.05 [95% CI, 0.01, 0.09])and a decreased number of new or enlarging T2 lesions over the treatment period (1 mg ozanimod,1.58; 0.5 mg ozanimod, 2.05; RR, 0.49 [95% CI, 0.19, 0.79]). No significant difference in causing adverse events between 1 and 0.5 mg was found.Conclusions: Our meta-analysis found that, with favorable safety performance, the use of ozanimod as a treatment of relapsing-remitting multiple sclerosis in adults was associated with a significant reduction of the annualized relapse rate during the treatment period, decreased number of gadolinium-enhancing lesions at the end of the trial, and lowered number of new or enlarging T2 lesions over the treatment period. Ozanimod 1 mg outperformed 0.5 mg dose in efficacy without increasing the risk of adverse events.

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Efficacy and tolerability of oral versus injectable disease-modifying therapies for multiple sclerosis in clinical practice

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/2055217316677868 ◽

2016 ◽

Vol 2 ◽

pp. 205521731667786 ◽

Cited By ~ 2

Author(s):

Erin E Longbrake ◽

Anne H Cross ◽

Amber Salter

Keyword(s):

Multiple Sclerosis ◽

Clinical Practice ◽

Proportional Hazards ◽

Dimethyl Fumarate ◽

Cox Proportional Hazards ◽

Oral Disease ◽

Sensitivity Analyses ◽

Drug Discontinuation ◽

Disease Modifying Therapies ◽

Disease Modifying

Background The advent of oral disease-modifying therapies fundamentally changed the treatment of multiple sclerosis. Nevertheless, impressions of their relative efficacy and tolerability are primarily founded on expert opinion. Objective The purpose of this study was to determine whether oral disease-modifying therapies were better tolerated and/or more effective for controlling multiple sclerosis compared to injectable therapies in clinical practice. Methods Single-center, retrospective cohort study. 480 patients initiated oral (fingolimod, teriflunomide, or dimethyl fumarate) or injectable therapy between March 2013–March 2015 and follow-up data was collected for 5–31 months. Outcomes included on-drug multiple sclerosis activity and drug discontinuation. Cox proportional hazards models were used to control for baseline differences and sensitivity analyses using propensity-weighted matching were performed. Results A higher proportion of teriflunomide-treated patients experienced multiple sclerosis activity compared to those treated with injectable therapies ( p = 0.0053) in the adjusted model. Breakthrough multiple sclerosis was equally prevalent among fingolimod and dimethyl fumarate-treated compared to injectable therapy-treated patients. Of patients initiating a disease-modifying therapy, 32–46% discontinued or switched treatments during the study. After controlling for baseline differences, discontinuation rates were comparable across treatment groups. Conclusions In this cohort, oral and injectable disease-modifying therapies were equally well tolerated, but teriflunomide appeared less effective for controlling multiple sclerosis activity than injectable therapies. Further study is needed.

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Comparative analysis of dimethyl fumarate and fingolimod in relapsing–remitting multiple sclerosis

Journal of Neurology ◽

10.1007/s00415-020-10226-6 ◽

2020 ◽

Author(s):

Johannes Lorscheider ◽

Pascal Benkert ◽

Carmen Lienert ◽

Peter Hänni ◽

Tobias Derfuss ◽

...

Keyword(s):

Multiple Sclerosis ◽

Dimethyl Fumarate ◽

Oral Disease ◽

Relapsing Remitting ◽

Treatment Naïve ◽

Baseline Characteristics ◽

Remitting Multiple Sclerosis ◽

Incident Rate ◽

Relapsing Remitting Multiple Sclerosis ◽

Relapse Rates

Abstract Background Dimethyl fumarate and fingolimod are oral disease modifying treatments (DMTs) that reduce relapse activity and slow disability worsening in relapsing–remitting multiple sclerosis (RRMS). Objective To compare the effectiveness of dimethyl fumarate and fingolimod in a real-world setting, where both agents are licensed as a first-line DMT for the treatment of RRMS. Methods We identified patients with RRMS commencing dimethyl fumarate or fingolimod in the Swiss Federation for Common Tasks of Health Insurances (SVK) Registry between August 2014 and July 2019. Propensity score-matching was applied to select subpopulations with comparable baseline characteristics. Relapses and disability outcomes were compared in paired, pairwise-censored analyses. Results Of the 2113 included patients, 1922 were matched (dimethyl fumarate, n = 961; fingolimod, n = 961). Relapse rates did not differ between the groups (incident rate ratio 1.0, 95%CI 0.8–1.2, p = 0.86). Moreover, no difference in the hazard of 1-year confirmed disability worsening (hazard ratio [HR] 0.9; 95%CI 0.6–1.6; p = 0.80) or disability improvement (HR 0.9; 95%CI 0.6–1.2; p = 0.40) was detected. These findings were consistent both for treatment-naïve patients and patients switching from another DMT. Conclusion Dimethyl fumarate and fingolimod have comparable effectiveness regarding reduction of relapses and disability worsening in RRMS.

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Atypical Multiple Sclerosis Lesions or Progressive Multifocal Leukoencephalopathy Lesions: That Is the Question

Journal of Investigative Medicine High Impact Case Reports ◽

10.1177/2324709620939802 ◽

2020 ◽

Vol 8 ◽

pp. 232470962093980 ◽

Cited By ~ 1

Author(s):

Stefania Federica De Mercanti ◽

Dario Gned ◽

Manuela Matta ◽

Marco Iudicello ◽

Emanuele Franchin ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Progressive Multifocal Leukoencephalopathy ◽

Case Reports ◽

Brain Mri ◽

Brain Magnetic Resonance Imaging ◽

Dimethyl Fumarate ◽

Diagnostic Process ◽

Suspected Case ◽

Fluid Analysis

Progressive multifocal leukoencephalopathy (PML) is a serious infective disease of the central nervous system that may occur in case of severe immunosuppression or after some treatment for multiple sclerosis (MS) with natalizumab, dimethyl fumarate, and fingolimod. In these case reports, we highlight the importance of differential diagnosis between PML and MS lesions in order to provide rapidly the best treatment option, by discussing the finding of brain (magnetic resonance imaging) MRI suggestive for PML in 2 MS patients, one treated with dimethyl fumarate and the other during natalizumab withdrawal. In both cases, although brain MRI was highly suggestive for PML, the detection of John Cunningham virus-DNA copies in cerebrospinal fluid resulted in negative result. These case reports illustrate the diagnostic process in case of suspected PML, as both patients were diagnosed with suspected PML during a routine brain MRI control, and highlights the importance of providing a strict brain MRI follow-up during dimethyl fumarate treatment, although only a few cases of PML during this therapy have been detected, and during natalizumab suspension phase. In clinical practice, in case of a radiologically suspected case of PML, although not confirmed by the cerebrospinal fluid analysis, the best approach could be to perform a close radiological and clinical monitoring before starting a new MS therapy.

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