Kevin Bigaut
@chru-strasbourg.fr
Les Hpitaux Universitaires de Strasbourg
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Guillaume Jouvenot, Guilhem Courbon, Mathilde Lefort, Fabien Rollot, Romain Casey, Emmanuelle Le Page, Laure Michel, Gilles Edan, Jérome de Seze, Laurent Kremer,et al.
American Medical Association (AMA)
ImportanceA recent randomized clinical trial concluded that discontinuing medium-efficacy therapy might be a reasonable option for older patients with nonactive multiple sclerosis (MS), but there is a lack of data on discontinuing high-efficacy therapy (HET). In younger patients, the discontinuation of natalizumab and fingolimod is associated with a risk of rebound of disease activity.ObjectiveTo determine whether discontinuing HET in patients 50 years and older with nonactive MS is associated with an increased risk of relapse compared with continuing HET.Design, Setting, and ParticipantsThis observational cohort study used data from 38 referral centers from the French MS registry (Observatoire Français de la Sclérose en Plaques [OFSEP] database). Among 84704 patients in the database, data were extracted for 1857 patients 50 years and older with relapsing-remitting MS treated by HET and with no relapse or magnetic resonance imaging activity for at least 2 years. After verification of the medical records, 1620 patients were classified as having discontinued HET or having remained taking treatment and were matched 1:1 using a dynamic propensity score (including age, sex, disease phenotype, disability, treatment of interest, and time since last inflammatory activity). Patients were included from February 2008 to November 2021, with a mean (SD) follow-up of 5.1 (2.9) years. Data were extracted in June 2022.ExposuresNatalizumab, fingolimod, rituximab, and ocrelizumab.Main Outcomes and MeasuresTime to first relapse.ResultsOf 1620 included patients, 1175 (72.5%) were female, and the mean (SD) age was 54.7 (4.8) years. Among the 1452 in the HET continuation group and 168 in the HET discontinuation group, 154 patients in each group were matched using propensity scores (mean [SD] age, 57.7 [5.5] years; mean [SD] delay since the last inflammatory activity, 5.6 [3.8] years; mean [SD] follow-up duration after propensity score matching, 2.5 [2.1] years). Time to first relapse was significantly reduced in the HET discontinuation group compared with the HET continuation group (hazard ratio, 4.1; 95% CI, 2.0-8.5; P < .001) but differed between HETs, with a hazard ratio of 7.2 (95% CI, 2.1-24.5; P = .001) for natalizumab, 4.5 (95% CI, 1.3-15.5; P = .02) for fingolimod, and 1.1 (95% CI, 0.3-4.8; P = .85) for anti-CD20 therapy.Conclusion and RelevanceAs in younger patients, in patients 50 years and older with nonactive MS, the risk of relapse increased significantly after stopping HETs that impact immune cell trafficking (natalizumab and fingolimod). There was no significant increase in risk after stopping HETs that deplete B-cells (anti-CD20 therapy). This result may inform decisions about stopping HETs in clinical practice.
Augustin Moreau, Ioanna Kolitsi, Laurent Kremer, Marie Fleury, Livia Lanotte, François Sellal, Claude Gaultier, Guido Ahle, Sylvie Courtois, Andreas Fickl,et al.
Elsevier BV
Nolwenn Krief, René Gabriel, Cécile Cauquil, David Adams, Guillaume Fargeot, Thierry Maisonobe, David Osman, Matthieu Schmidt, Jean-Baptiste Chanson, Kevin Bigaut,et al.
Springer Science and Business Media LLC
L. Gauer, K. Bigaut, É. Berger, M. Debouverie, T. Moreau, and J. de Sèze
Elsevier BV
Juliette Pelle, Anais R. Briant, Pierre Branger, Nathalie Derache, Charlotte Arnaud, Christine Lebrun-Frenay, Mikael Cohen, Lydiane Mondot, Jerome De Seze, Kevin Bigaut,et al.
Springer Science and Business Media LLC
Michael Levraut, Sabine Laurent-Chabalier, Xavier Ayrignac, Kévin Bigaut, Manon Rival, Sanae Squalli, Hélène Zéphir, Tifanie Alberto, Jean-David Pekar, Jonathan Ciron,et al.
Ovid Technologies (Wolters Kluwer Health)
Background and ObjectivesKappa free light chains (KFLC) seem to efficiently diagnose MS. However, extensive cohort studies are lacking to establish consensus cut-offs, notably to rule out non-MS autoimmune CNS disorders. Our objectives were to (1) determine diagnostic performances of CSF KFLC, KFLC index, and KFLC intrathecal fraction (IF) threshold values that allow us to separate MS from different CNS disorder control populations and compare them with oligoclonal bands' (OCB) performances and (2) to identify independent factors associated with KFLC quantification in MS.MethodsWe conducted a retrospective multicenter study involving 13 French MS centers. Patients were included if they had a noninfectious and nontumoral CNS disorder, eligible data concerning CSF and serum KFLC, albumin, and OCB. Patients were classified into 4 groups according to their diagnosis: MS, clinically isolated syndrome (CIS), other inflammatory CNS disorders (OIND), and noninflammatory CNS disorder controls (NINDC).ResultsOne thousand six hundred twenty-one patients were analyzed (675 MS, 90 CIS, 297 OIND, and 559 NINDC). KFLC index and KFLC IF had similar performances in diagnosing MS from nonselected controls and OIND (p= 0.123 andp= 0.991 for area under the curve [AUC] comparisons) and performed better than CSF KFLC (p< 0.001 for all AUC comparisons). A KFLC index of 8.92 best separated MS/CIS from the entire nonselected control population, with better performances than OCB (p< 0.001 for AUC comparison). A KFLC index of 11.56 best separated MS from OIND, with similar performances than OCB (p= 0.065). In the multivariate analysis model, female gender (p= 0.003), young age (p= 0.013), and evidence of disease activity (p< 0.001) were independent factors associated with high KFLC index values in patients with MS, whereas MS phenotype, immune-modifying treatment use at sampling, and the FLC analyzer type did not influence KFLC index.DiscussionKFLC biomarkers are efficient tools to separate patients with MS from controls, even when compared with other patients with CNS autoimmune disorder. Given these results, we suggest using KFLC index or KFLC IF as a criterion to diagnose MS.Classification of EvidenceThis study provides Class III evidence that KFLC index or IF can be used to differentiate patients with MS from nonselected controls and from patients with other autoimmune CNS disorders.
T. Bogdan, T. Wirth, A. Iosif, A. Schalk, S. Montaut, C. Bonnard, G. Carre, O. Lagha-Boukbiza, C. Reschwein, E. Albugues,et al.
Springer Science and Business Media LLC
T. Bogdan, S. El Ghannudi, S. Demuth, L. Kremer, J. De Seze, and K. Bigaut
Elsevier BV
Dafni Birmpili, Imane Charmarke Askar, Kévin Bigaut, and Dominique Bagnard
MDPI AG
Multiple Sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system which is characterized by demyelinating lesions and axonal damage. MS is a complex disease characterized by important pathophysiological heterogeneity affecting the clinical appearance, progression and therapeutic response for each patient. Therefore, there is a strong unmet need to define specific biomarkers that will reflect the different features of the disease. Experimental autoimmune encephalomyelitis (EAE) is the most commonly used experimental model for the study of MS, as it resembles the pathological features of human MS in many aspects and has allowed for the elucidation of pathogenesis pathways and the validation of certain targets for MS therapies. In this review, we discuss clinically relevant MS molecular biomarkers, divided into five groups based on the key pathological hallmarks of MS: inflammation, blood–brain barrier disruption, myelin and axonal damage, gliosis and, ultimately, repair mechanisms. To address the feasibility of translation between the animal model and human disease, we present an overview of several molecular biomarkers of each category and compare their respective deregulation patterns. We conclude that, like any disease animal model, EAE models can sometimes fail to mimic the entire spectrum of human disease, but they can nonetheless recapitulate the disease’s primary hallmarks. We show that the EAE model is a valuable tool for understanding MS physiopathological mechanisms and for identifying biomarkers fundamental for drug development.
Maximilian Einsiedler, Laurent Kremer, Marie Fleury, Nicolas Collongues, Jérôme De Sèze, and Kévin Bigaut
Springer Science and Business Media LLC
Anti-CD20 monoclonal antibodies are recently introduced treatments in progressive MS and real-world data are lacking. The aim of this study is to describe a cohort of progressive MS patients treated with ocrelizumab or rituximab in a real-world setting. This monocentric prospective cohort study at the University Hospital of Strasbourg included patients with primary progressive or secondary progressive MS that started treatment with anti-CD20 antibodies before June 2019. Every six months, patients were assessed using the following standardized clinical evaluations: Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9-HPT) and Symbol Digit Modalities Test (SDMT). The primary analysis considered EDSS progression (of at least 1.0 if EDSS ≤ 5.5 and at least 0.5 if EDSS ≥ 6.0). We included 108 patients, with a median age upon inclusion of 53 years [48.0–58.0]. 72% were classified as primary progressive forms. Median baseline EDSS was 6.0 [4.0–6.5]. EDSS was significantly correlated with T25FW, SDMT and 9-HPT. Following 2 years of treatment, 38.9% of patients presented EDSS progression compared to baseline. Our large cohort confirms tolerance of these treatments in a real-world setting. Standardized clinical assessments could improve detection of deteriorating patients. Further studies are needed to establish predictive factors.
Bhagteshwar Singh, Suzannah Lant, Sofia Cividini, Jonathan W. S. Cattrall, Lynsey C. Goodwin, Laura Benjamin, Benedict D. Michael, Ayaz Khawaja, Aline de Moura Brasil Matos, Walid Alkeridy,et al.
PLoS ONE Public Library of Science (PLoS)
Background Neurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome. Methods We conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models. Results We included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67–82]), than encephalopathy (54% [42–65]). Intensive care use was high (38% [35–41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27–32]. The hazard of death was comparatively lower for patients in the WHO European region. Interpretation Neurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission.
Stanislas Demuth, Thomas Bogdan, Laurent Kremer, Livia Lanotte, Nicolas Collongues, Jérôme de Seze, and Kévin Bigaut
Springer Science and Business Media LLC
We report the therapeutic response of a challenging case of advanced Susac syndrome. The disease began in 2008 at age 23. This male patient presented headaches and transient aphasia and dysesthesias of the right upper limb. Brain MRI showed multiple white matter lesions without gadolinium enhancement (GdE). Some involved the corpus callosum (snowball lesions; Fig. 1). The study of CSF showed 1.26 g/L of proteins and a pleiocytosis (19 mononucleated leukocytes/mm3) without intrathecal immunoglobulins synthesis. There were no ophthalmic or auditory impairments at this time. We achieved clinical remission with intravenous (IV) corticosteroids and a subsequent oral maintenance treatment. A little time after the end of the corticosteroids, he presented a right branch retinal artery occlusion (BRAO) associated to attention and executive disturbances. Neck and cerebral angiography found no sign of large vessel vasculitis. The C-reactive protein was normal. Our microbial screening, including Lyme disease, syphilis, tuberculosis, TBE, JC virus, HSV, VZV, HIV, viral hepatitis, enterovirus, parvovirus, and immunological screening, including cryoglobulinemia, antinuclear, anti-phospholipids, anti-gastric and antineuronal autoantibodies, Schirmer test and salivary gland biopsy, were negative. We did not look for antiendothelial cell antibodies. There was no proteinuria. Overall, this corresponded to the diagnosis of probable Susac syndrome according to the 2016 diagnosis criterias [1]. Corticosteroids were resumed along with cyclophosphamide pulses (750 mg/m2; Fig. 1). However, he presented a left central retinal artery occlusion (CRAO) 5 months later under this treatment (0.5 mg/Kg of corticosteroids), which prompted the adjunction of intravenous immunoglobulins (IVIg) infusions. Nevertheless, he presented bilateral hearing impairment with tinnitus the year after, supported by a pure-tone audiogram showing a mean loss of 26 dB and 42 dB of both conductions of the right and left ears, respectively. This completed the actual diagnosis criterias of definite Susac syndrome [1]. Osteoporosis limited the use of corticosteroids. After 12 cycles, we switched cyclophosphamide to mycophenolate mofetil (1 g/day). The patient endured several cerebral relapses presenting as confusion, treated by IV corticosteroids. A third and fourth lumbar puncture in 2011 and 2019 showed hyperproteinorachia with normal white blood cell counts (1.07 g/L and 0.82 g/L, respectively). Ultimately, he developed a diffuse brain atrophy and multiple impairments, i.e., dementia, spastic paraparesis, cerebellar ataxia and dysarthria. Recent relapses have led to further therapeutic changes. The patient had 12 further cycles of cyclophosphamide, switched to azathioprine (150 mg/ day), then to rituximab (1 g every 6 months). Leptomeningeal gadolinium enhancement persisted after 3 cycles of rituximab, with the appearance of several parenchymal GdE lesions (Fig. 2). As the patient’s cognition, dysarthria and ataxia deteriorated, we made a switch to tocilizumab (600 mg each month). However, the patient kept deteriorating with a sudden visual impairment 3 months later. Brain MRI showed a lacunar infarction and profuse leptomeningeal GdE (Fig. 2). The vision improved after IV corticosteroids, five plasma exchanges and IVIg. We switched to infliximab (5 mg/Kg each month). There was no GdE left 6 weeks and 5 months later (Fig. 2). The patient had no clinical relapses ever since. Brain MRI can show abnormalities in the white matter (supraor infratentorial), gray matter or leptomeninges [7]. Typical lesions are “snowballs” in the central callosum * Kévin Bigaut kevin.bigaut@chru-strasbourg.fr
Kévin Bigaut, Laurent Kremer, Thibaut Fabacher, Guido Ahle, Mathilde Goudot, Marie Fleury, Claude Gaultier, Sylvie Courtois, Nicolas Collongues, and Jérôme de Seze
Springer Science and Business Media LLC
Exit strategy after natalizumab cessation in multiple sclerosis (MS) is a crucial point because the risk of disease reactivation is high during this period. The objective of this observational study was to compare ocrelizumab to fingolimod after natalizumab cessation in patients with relapsing–remitting multiple sclerosis (RRMS). All RRMS patients starting fingolimod or ocrelizumab within 6 weeks after natalizumab cessation were included. The primary endpoint was the annualized relapse rate (ARR) at 1 year. We included 54 patients receiving fingolimod and 48 patients receiving ocrelizumab after natalizumab cessation. In multivariate analysis, ARR at 1 year was significantly lower in the ocrelizumab group than in the fingolimod group (0.12 ± 0.39 versus 0.41 ± 0.71, p = 0.026), i.e. a 70.7% lower relapse rate. The cumulative probability of relapses at 1 year was 31.5% (17/54 patients) with fingolimod and 10.4% (5/48 patients) with ocrelizumab, corresponding to a hazard ratio of 3.4 (95% confidence interval: 1.1–11, p = 0.04). Our results suggest ocrelizumab is potentially a better exit strategy than fingolimod after natalizumab cessation.
Edouard Januel, Jérôme De Seze, Patrick Vermersch, Elisabeth Maillart, Bertrand Bourre, Julie Pique, Xavier Moisset, Caroline Bensa, Adil Maarouf, Jean Pelletier,et al.
SAGE Publications
Introduction: Recent studies suggested that anti-CD20 and fingolimod may be associated with lower anti-spike protein-based immunoglobulin-G response following COVID-19 vaccination. We evaluated if COVID-19 occurred despite vaccination among patients with multiple sclerosis (MS) and neuromyelitis optica (NMO), using the COVISEP registry. Case series: We report 18 cases of COVID-19 after two doses of BNT162b2-vaccination, 13 of which treated with anti-CD20 and four with fingolimod. COVID-19 severity was mild. Discussion: These results reinforce the recommendation for a third COVID-19 vaccine dose among anti-CD20 treated patients and stress the need for a prospective clinical and biological study on COVID-19 vaccine efficacy among MS and NMO patients.
Maximilian Einsiedler, Paul Voulleminot, Stanislas Demuth, Pauline Kalaaji, Thomas Bogdan, Lucas Gauer, Cécile Reschwein, Aleksandra Nadaj-Pakleza, Jérôme de Sèze, Laurent Kremer,et al.
Springer Science and Business Media LLC
The recent lockdown due to the COVID-19 pandemic has been linked to a higher incidence of psychiatric manifestations and substance abuse. The recreative use of nitrous oxide is more and more widespread and neurological complications are frequent. We report clinical characteristics and biological findings of five consecutive patients presenting to our tertiary care center between April 2020 and February 2021 with various neurological symptoms occurring after recent nitrous oxide abuse. Our patients presented with subacute combined degeneration of the spinal cord (4/5 patients) or with acute inflammatory demyelinating polyneuropathy (1/5 patients). No patient had reduced vitamin B-12 titer, but all had elevated blood levels of homocysteine and methylmalonic acid. This reflects the functional deficit in vitamin B-12 that can be linked to nitrous oxide consumption. After vitamin B-12 supplementation, clinical signs regressed at least partially in all 5 patients. We report an elevated incidence of neurological complications of nitrous oxide abuse occurring during the recent COVID-19 lockdown. Nitrous oxide abuse should be tracked down in patients presenting with compatible neurological symptoms and elevated homocysteinemia. Vitamin B-12 should be supplemented as soon as the diagnosis is made.
Sandra Vukusic, Romain Marignier, Jonathan Ciron, Bertrand Bourre, Mikael Cohen, Romain Deschamps, Maxime Guillaume, Laurent Kremer, Julie Pique, Clarisse Carra-Dalliere,et al.
SAGE Publications
Background: In 2020, the French Multiple Sclerosis (MS) Society (SFSEP) decided to develop a national evidence-based consensus on pregnancy in MS. As neuromyelitis optica spectrum disorders (NMOSD) shares a series of commonalities with MS, but also some significant differences, specific recommendations had to be developed. Objectives: To establish recommendations on pregnancy in women with NMOSD. Methods: The French Group for Recommendations in Multiple Sclerosis (France4MS) reviewed PubMed and universities databases (January 1975 through June 2021). The RAND/UCLA appropriateness method, which was developed to synthesise the scientific literature and expert opinions on health care topics, was used to reach a formal agreement. Fifty-six MS experts worked on the full-text review and initial wording of recommendations. A sub-group of nine NMOSD experts was dedicated to analysing available data on NMOSD. A group of 62 multidisciplinary healthcare specialists validated the final proposal of summarised evidence. Results: A strong agreement was reached for all 66 proposed recommendations. They cover diverse topics, such as pregnancy planning, follow-up during pregnancy and postpartum, delivery routes, loco-regional analgesia or anaesthesia, prevention of postpartum relapses, breastfeeding, vaccinations, reproductive assistance, management of relapses, and disease-modifying treatments. Conclusion: Physicians and patients should be aware of the new and specific evidence-based recommendations of the French MS Society for pregnancy in women with NMOSD. They should help harmonise counselling and treatment practise, allowing for better individualised choices.
Sandra Vukusic, Clarisse Carra-Dalliere, Jonathan Ciron, Elisabeth Maillart, Laure Michel, Emmanuelle Leray, Anne-Marie Guennoc, Bertrand Bourre, David Laplaud, Géraldine Androdias,et al.
SAGE Publications
Objective: The objective of this study was to develop evidence-based recommendations on pregnancy management for persons with multiple sclerosis (MS). Background: MS typically affects young women in their childbearing years. Increasing evidence is available to inform questions raised by MS patients and health professionals about pregnancy issues. Methods: The French Group for Recommendations in Multiple Sclerosis (France4MS) reviewed PubMed and university databases (January 1975 through June 2021). The RAND/UCLA appropriateness method was developed to synthesise the scientific literature and expert opinions on healthcare topics; it was used to reach a formal agreement. Fifty-six MS experts worked on the full-text review and initial wording of recommendations. A group of 62 multidisciplinary healthcare specialists validated the final proposal of summarised evidence. Results: A strong agreement was reached for all 104 proposed recommendations. They cover diverse topics, such as pregnancy planning, follow-up during pregnancy and postpartum, delivery routes, locoregional analgesia or anaesthesia, prevention of postpartum relapses, breastfeeding, vaccinations, reproductive assistance, management of relapses and disease-modifying treatments. Conclusion: The 2022 recommendations of the French MS society should be helpful to harmonise counselling and treatment practice for pregnancy in persons with MS, allowing for better and individualised choices.
Z. Böcskei, E. Viinikka, L. Dormegny, K. Bigaut, and C. Speeg
Elsevier BV
Ocular paraneoplastic syndromes are rare conditions that can affect any part of the eye at any age. Thus, every ophthalmologist should be familiar with their management, as some of them may reveal severe, life-threatening conditions. These consist overwhelmingly of neuro-ophthalmological manifestations, affecting the optic nerve (paraneoplastic optic neuritis), retina (paraneoplastic retinopathy) or neurological pathways generating eye movements (saccadic intrusion, oculomotor palsy, nystagmus...); occasionally, they involve the anterior segment, orbit or uveal tract. As some of these manifestations appear to be quite common and non-specific, any systemic or especially neurologic comorbidities should increase suspicion. Treatment relies first on oncologic management, and then often more targeted therapy for the associated immune involvement.
Lucie Isoline Pisella, Sara Fernandes, Guilhem Solé, Tanya Stojkovic, Céline Tard, Jean-Baptiste Chanson, Françoise Bouhour, Emmanuelle Salort-Campana, Guillemette Beaudonnet, Louise Debergé,et al.
Springer Science and Business Media LLC
Abstract Background Due to their health condition, patients with neuromuscular diseases (NMD) are at greater risk of developing serious complications with COVID-19. The objective of this study was to analyze the prevalence of COVID-19 among NMD patients and the risk factors for its impact and severity during the first wave of the pandemic. Clinical data were collected from NMD-COVID-19 patients, between March 25, 2020 and May 11, 2020 in an anonymous survey carried out by expert physicians from the French Health Care Network Filnemus. Results Physicians reported 84 patients, including: 34 with myasthenia gravis, 27 with myopathy and 23 with neuropathy. COVID-19 had no effect on NMD for 48 (58%) patients and 48 (58%) patients developed low COVID-19 severity. COVID-19 caused the death of 9 (11%) NMD patients. Diabetic patients were at greater risk of dying. Patients with diabetes, hypertension or severe forms of NMD had a higher risk of developing a moderate or severe form of COVID-19. In our cohort, corticosteroids and other immunosuppressants were not significantly associated with higher COVID-19 severity for acquired NMD. Conclusion During this period, a small percentage of French NMD patients was affected by COVID-19 compared to the general French population and COVID-19 had a limited short-term effect on them. Diabetes, hypertension and a severe degree of NMD were identified as risk factors of unfavorable outcome following COVID-19. Conversely, in our cohort of patients with acquired NMD, corticosteroids or other immunosuppressants did not appear to be risk factors for more severe COVID-19.
K. Bigaut, L. Kremer, M. Fleury, L. Lanotte, N. Collongues, and J. de Seze
Elsevier BV
Objective: To analyze the humoral response after COVID-19 vaccination in patients with multiple sclerosis (MS) according to disease-modifying treatments (DMTs) and in comparison with the humoral response after SARS-CoV-2 infection.
Methods: We included 28 MS patients with serological results after COVID-19 vaccination (Pfizer-BioNTech or Moderna ARNm) and 61 MS patients with serological results after COVID-19 (COVID-19 group) among patients followed up at the MS Center of Strasbourg, France, between January and April 2021. The primary endpoint was the IgG index according to DMTs (anti-CD20 mAb, sphingosine 1-phosphate receptor [S1PR] modulator and other treatments) and COVID-19 vaccine or COVID-19 groups.
Results: In the vaccinated MS patients, the median IgG index was lower in patients treated with anti-CD20 mAb and in patients treated with S1PR modulator compared to patients receiving other or no DMTs (4.80 [1.58 - 28.6], 16.5 [16.3 - 48.5], 1116 [434 - 1747] and 1272 [658 - 1886], respectively, p<0.001). Similar results were found for MS patients after COVID-19.
Conclusions: Patients with MS and treated with S1PR modulators or anti-CD20 mAb had a reduced humoral response after COVID-19 vaccine.
Kévin Bigaut, Laurent Kremer, Thibaut Fabacher, Livia Lanotte, Marie-Celine Fleury, Nicolas Collongues, and Jerome de Seze
Ovid Technologies (Wolters Kluwer Health)
ObjectiveTo compare the humoral response after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with multiple sclerosis (MS) receiving different disease-modifying treatments (DMTs).MethodsPatients with MS with coronavirus disease 2019 (COVID-19) and available anti–SARS-CoV-2 serology were included. The primary endpoint was the anti–SARS-CoV-2 immunoglobulin G (IgG) index. The multivariate analysis was adjusted for COVID-19 severity, SARS-CoV-2 PCR result, and the time between COVID-19 onset and the serology.ResultsWe included 61 patients with available IgG index. The IgG index was lower in patients with fingolimod or anti-CD20 monoclonal antibodies compared with patients without treatment (p < 0.01), patients with interferon β-1a or glatiramer (p < 0.01), and patients with another DMT (p = 0.01). The IgG index was correlated with the time between COVID-19 onset and serology (r = −0.296 [−0.510; −0.0477], p = 0.02).ConclusionsHumoral response after COVID-19 was lower in patients with MS with fingolimod or anti-CD20 mAb. These patients could therefore be at risk of recurrent infection and could benefit from anti–SARS-CoV-2 vaccination. The humoral response after vaccination and the delay before vaccination need to be evaluated.Classification of EvidenceThis study provides Class IV evidence that patients treated with fingolimod or anti-CD20 monoclonal antibodies for MS have a lower humoral response after COVID-19 compared with patients without DMTs or with another DMTs.
Mikael Cohen, Lydiane Mondot, Florence Bucciarelli, Béatrice Pignolet, David-Axel Laplaud, Sandrine Wiertlewski, Bruno Brochet, Aurélie Ruet, Gilles Defer, Nathalie Derache,et al.
SAGE Publications
Background: There are few head-to-head studies to compare highly active treatments in multiple sclerosis (MS) Objective: The aim of this study was to compare the effectiveness between natalizumab (NTZ) and fingolimod (FTY) in active relapsing–remitting MS Method: Best Escalation STrategy in Multiple Sclerosis (BEST-MS) is a multicentric, prospective study with a 12-month follow-up including patients with active MS. Treatment choice was at the discretion of physician. Clinical and magnetic resonance imaging (MRI) data were collected at baseline and at 12 months. The primary outcome was the proportion of patients reaching no evidence of disease activity (NEDA) at 12 months. Secondary outcomes included annualized relapse rate and MRI activity. Results: A total of 223 patients were included (NTZ: 109 and FTY: 114). Treatment groups were well balanced at baseline. Proportion of NEDA patients was 47.8% in NTZ group versus 30.4% in FTY group ( p = 0.015). This superiority was driven by annualized relapse rate and MRI activity. In the multivariate analysis, treatment group was the only factor associated with NEDA at 12 months with a lower probability in FTY group (odds ratio (OR) = 0.49, p = 0.029). Conclusion: BEST-MS is a prospective study that compared head-to-head the effectiveness of NTZ and FTY in active relapsing–remitting MS. Our results suggest a superiority of NTZ over FTY.
Kévin Bigaut, Mikaël Cohen, Françoise Durand-Dubief, Elisabeth Maillart, Evelyne Planque, Hélène Zephir, Christine Lebrun-Frenay, and Jérôme de Seze
Elsevier BV
BACKGROUND
Today, there are no recommendations on switching disease-modifying treatments (DMTs) in multiple sclerosis (MS).
OBJECTIVES
To establish guidelines on switching DMTs MS.
METHODS
A Steering Committee composed of seven MS experts from the French Group for Recommendations in Multiple Sclerosis (France4MS) defined 15 proposals. These proposals were then submitted to a Rating Group, composed of 48 French MS experts, for evaluation. The proposals were classified as 'appropriate', 'inappropriate' or 'uncertain'.
RESULTS
Switching from a first-line therapy to another first-line therapy or a second-line therapy could be done without a washout period. Switching from a second-line therapy to a first-line therapy could be done without a washout period with fingolimod or natalizumab, after 3 months with ocrelizumab or mitoxantrone, and, if disease activity occurs with alemtuzumab or cladribine. The switch from a second-line therapy to another second-line therapy could be done after a washout period of 1 month with fingolimod or natalizumab, after 3 months with ocrelizumab, after 6 months with mitoxantrone, and, if disease activity occurs, with alemtuzumab or cladribine.
CONCLUSION
This expert consensus approach provides physicians with some guidelines on optimizing the benefit/risk ratio when switching DMTs in patients with MS.
Jérôme de Seze and Kévin Bigaut
Elsevier BV
Kévin Bigaut, Thibaut Fabacher, Laurent Kremer, Jean-Claude Ongagna, Arnaud Kwiatkowski, François Sellal, Didier Ferriby, Sylvie Courtois, Patrick Vermersch, Nicolas Collongues,et al.
SAGE Publications
Background: Data are needed on long-term effect of natalizumab (NTZ) in relapsing-remitting multiple sclerosis (RRMS). Objectives: To evaluate the time of onset of secondary progressive phase in patients with an RRMS treated with NTZ and to investigate predictive factors. Methods: TYSTEN is an observational study. Patients starting NTZ between 2007 and 2012 were included and followed up until October 2018. Relapses, Expanded Disability Status Scale (EDSS) scores, and results of brain magnetic resonance imaging (MRI) were collected each year. Data were used to estimate the cumulative probability of several poor outcomes such as secondary progressive multiple sclerosis (SPMS) conversion, EDSS worsening, EDSS 4.0, and EDSS 6.0. Results: 770 patients were included. The mean follow-up duration was 97 months and the mean time exposure to NTZ was 66 months. At 10 years, the cumulative probability of SPMS was 27.7%. Predictive factors for poor outcomes were a ⩾1-point increase in EDSS score from baseline, new T2 lesion or T1 gadolinium-enhancing lesion, the occurrence of relapse at 1 or 2 years and No Evidence of Disease Activity (NEDA-3; no relapse, no new T2 or T1 gadolinium-enhancing lesions, no progression) was a protective factor. Conclusion: In our cohort of patients treated with NTZ, poor outcomes were infrequent and are driven by disease activity.