DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

Fine Particulate Matter Related to Multiple Sclerosis Relapse in Young Patients

International audienceObjective: Particulate matter (PM) of aerodynamic diameter smaller than 10 µm (PM 10) has been associated with multiple sclerosis (MS) relapse. However, the impact of smaller PM with a greater ability to penetrate human organism has never been assessed. We evaluated the impact of PM smaller than 2.5 µm (PM 2.5) on the risk of MS relapse. Material and Methods: In a case-crossover study, we included 2,109 consecutive hospitalizations likely due to MS relapse in day hospital in 5 MS centers in the Paris area from January 2009 to December 2013. For each hospitalization, the natural logarithm of the average weekly PM 2.5 concentrations (µg/m 3) at the patient's residence address during each of the 6 weeks (week[0] to week[−5]) preceding admission was compared with the concentration during the previous week, using a conditional logistic regression adjusted on temperature, flu-like syndrome rate, pollen count, and holiday period. Results: PM 2.5 average concentration during week[−3] was significantly associated with the risk of hospitalization for MS relapse [OR = 1.21 (CI 1.01;1.46)]. The association was stronger in patients younger than 30 years [OR=1.77 (CI 1.10; 2.83)]. Conclusion: Our study demonstrates an association between exposure to PM 2.5 and MS relapse, particularly in young people

Longitudinally Extensive Myelitis Associated With Immune Checkpoint Inhibitors

International audienceObjective: To define the characteristics and the outcome of myelitis associated with immune checkpoint inhibitors (ICIs).Methods: We performed a retrospective research in the databases of the French Pharmacovigilance Agency and the OncoNeuroTox network for patients who developed myelitis following treatment with ICIs (2011-2020). A systematic review of the literature was performed to identify similar cases.Results: We identified 7 patients who developed myelitis after treatment with ICIs (anti-PD1 [n = 6], anti-PD1 + anti-CTLA4 [n = 1]). Neurologic symptoms included paraparesis (100%), sphincter dysfunction (86%), tactile/thermic sensory disturbances (71%), and proprioceptive ataxia (43%). At the peak of symptom severity, all patients were nonambulatory. MRI typically showed longitudinally extensive lesions, with patchy contrast enhancement. CSF invariably showed inflammatory findings. Five patients (71%) had clinical and/or paraclinical evidence of concomitant cerebral, meningeal, caudal roots, and/or peripheral nerve involvement. Despite the prompt discontinuation of ICIs and administration of high-dose glucocorticoids (n = 7), most patients needed second-line immune therapies (n = 5) because of poor recovery or early relapses. At last follow-up, only 3 patients had regained an ambulatory status (43%). Literature review identified 13 previously reported cases, showing similar clinical and paraclinical features. All patients discontinued ICIs and received high-dose glucocorticoids, with the addition of other immune therapies in 8. Clinical improvement was reported for 10 patients.Conclusion: Myelitis is a rare but severe complication of ICIs that shows limited response to glucocorticoids. Considering the poor functional outcome associated with longitudinally extensive myelitis, strong and protracted immune therapy combinations are probably needed upfront to improve patient outcome and prevent early relapses

Brief Report: Impact of ART Classes on the Increasing Risk of Cerebral Small-Vessel Disease in Middle-Aged, Well-Controlled, cART-Treated, HIV-Infected Individuals

International audienceBackground: Cerebral small-vessel disease (CSVD) is a chronic disease accounting for one-third of strokes and the second etiology of dementia. Despite sustained immunovirological control, CSVD prevalence is doubled in middle-aged persons living with HIV (PLHIVs), even after adjustment for traditional cardiovascular risk factors. We aimed to investigate whether exposure to any antiretroviral drug class could be associated with an increasing risk of CSVD.Methods: The MicroBREAK-2 case-control study (NCT02210130) enrolled PLHIVs aged 50 years and older, treated with combined antiretroviral therapy for ≥5 years, with plasma HIV load controlled for ≥12 months. Cases were PLHIVs with radiologically defined CSVD, and controls were CSVD-free PLHIVs matched for age (±5 years), sex, and year of HIV diagnosis (±5 years). Multivariable conditional logistic regression analyses focused on cumulative exposure to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors and/or exposure to integrase inhibitors (yes or no), adjusted for hypertension, CD4 nadir, current CD4/CD8 ratio, and HIV transmission group.Results: Between May 2014 and April 2017, 77 cases and 77 controls (85.7% males) were recruited. PLHIVs' median age was 57.6 years, and median HIV diagnosis year was 1992. The increasing risk of CSVD was not associated with exposure to any ART class.Conclusion: No deleterious effect of ART class exposure on the risk of CSVD was found for middle-aged treated PLHIVs

Post-vaccine COVID-19 in patients with multiple sclerosis or neuromyelitis optica

International audienceIntroduction: 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

Cancer and multiple sclerosis: 2023 recommendations from the French Multiple Sclerosis Society

International audienceBackground: Epidemiological data reveal that 45% of persons with multiple sclerosis (PwMS) in France are more than 50 years. This population more than 50 is more susceptible to cancer, and this risk may be increased by frequent use of immunosuppressive drugs. Consequently, concerns have arisen about the potential increased risk of cancer in PwMS and how patients should be screened and managed in terms of cancer risk.Objective: To develop evidence-based recommendations to manage the coexistence of cancer and multiple sclerosis (MS).Methods: The French Group for Recommendations in MS collected articles from PubMed and university databases covering the period January 1975 through June 2022. The RAND/UCLA method was employed to achieve formal consensus. MS experts comprehensively reviewed the full-text articles and developed the initial recommendations. A group of multidisciplinary health care specialists then validated the final proposal.Results: Five key questions were addressed, encompassing various topics such as cancer screening before or after initiating a disease-modifying therapy (DMT), appropriate management of MS in the context of cancer, recommended follow-up for cancer in patients receiving a DMT, and the potential reintroduction of a DMT after initial cancer treatment. A strong consensus was reached for all 31 recommendations.Conclusion: These recommendations propose a strategic approach to managing cancer risk in PwMS

sj-docx-1-msj-10.1177_13524585231218149 – Supplemental material for COVID-19 outcomes in patients with multiple sclerosis: Understanding changes from 2020 to 2022

Supplemental material, sj-docx-1-msj-10.1177_13524585231218149 for COVID-19 outcomes in patients with multiple sclerosis: Understanding changes from 2020 to 2022 by Lina Jeantin, Edouard Januel, Pierre Labauge, Elisabeth Maillart, Jérôme de Seze, Hélène Zéphir, Jean Pelletier, Philippe Kerschen, Damien Biotti, Olivier Heinzlef, Laurent Guilloton, Caroline Bensa, Marie Théaudin, Sandra Vukusic, Olivier Casez, Aude Maurousset, David Laplaud, Eric Berger, Christine Lebrun-Frenay, Bertrand Bourre, Pierre Branger, Bruno Stankoff, Pierre Clavelou, Eric Thouvenot, Eric Manchon, Thibault Moreau, François Sellal, Mickaël Zedet, Caroline Papeix and Céline Louapre in Multiple Sclerosis Journal</p

sj-docx-4-msj-10.1177_13524585231223880 – Supplemental material for Cancer and multiple sclerosis: 2023 recommendations from the French Multiple Sclerosis Society

Supplemental material, sj-docx-4-msj-10.1177_13524585231223880 for Cancer and multiple sclerosis: 2023 recommendations from the French Multiple Sclerosis Society by Nicolas Collongues, Françoise Durand-Dubief, Christine Lebrun-Frenay, Bertrand Audoin, Xavier Ayrignac, Caroline Bensa, Kévin Bigaut, Bertrand Bourre, Clarisse Carra-Dallière, Jonathan Ciron, Gilles Defer, Arnaud Kwiatkowski, Emmanuelle Leray, Elisabeth Maillart, Romain Marignier, Guillaume Mathey, Nathalie Morel, Eric Thouvenot, Hélène Zèphir, Julie Boucher, Clémence Boutière, Pierre Branger, Angélique Da Silva, Sarah Demortière, Maxime Guillaume, Benjamin Hebant, Edouard Januel, Anne Kerbrat, Eric Manchon, Xavier Moisset, Alexis Montcuquet, Chloé Pierret, Julie Pique, Julien Poupart, Chloé Prunis, Thomas Roux, Perrine Schmitt, Géraldine Androdias and Mikael Cohen in Multiple Sclerosis Journal</p

sj-docx-2-msj-10.1177_13524585231223880 – Supplemental material for Cancer and multiple sclerosis: 2023 recommendations from the French Multiple Sclerosis Society

Supplemental material, sj-docx-2-msj-10.1177_13524585231223880 for Cancer and multiple sclerosis: 2023 recommendations from the French Multiple Sclerosis Society by Nicolas Collongues, Françoise Durand-Dubief, Christine Lebrun-Frenay, Bertrand Audoin, Xavier Ayrignac, Caroline Bensa, Kévin Bigaut, Bertrand Bourre, Clarisse Carra-Dallière, Jonathan Ciron, Gilles Defer, Arnaud Kwiatkowski, Emmanuelle Leray, Elisabeth Maillart, Romain Marignier, Guillaume Mathey, Nathalie Morel, Eric Thouvenot, Hélène Zèphir, Julie Boucher, Clémence Boutière, Pierre Branger, Angélique Da Silva, Sarah Demortière, Maxime Guillaume, Benjamin Hebant, Edouard Januel, Anne Kerbrat, Eric Manchon, Xavier Moisset, Alexis Montcuquet, Chloé Pierret, Julie Pique, Julien Poupart, Chloé Prunis, Thomas Roux, Perrine Schmitt, Géraldine Androdias and Mikael Cohen in Multiple Sclerosis Journal</p