Objective:
To investigate the efficacy of rituximab as rescue therapy in patients with relapsing-remitting multiple sclerosis (RRMS) and persistent disease activity confirmed by magnetic resonance ...imaging (MRI) despite immunosuppressive disease-modifying therapy (DMT).
Methods:
In this observational nationwide retrospective multicenter study, we first identified 351 off-label rituximab-treated patients through a cohort of 15,984 RRMS patients. In this group, we identified patients with disease activity prior to rituximab confirmed by MRI (one or more new T2 lesion and/or gadolinium-enhancing lesion) despite immunosuppressive DMT (fingolimod, natalizumab, or mitoxantrone) with a follow-up after rituximab initiation longer than 6 months. Outcome data were collected from the French Observatory of Multiple Sclerosis (OFSEP) register and medical charts.
Results:
A total of 50 patients were identified. Median rituximab treatment duration was 1.1 (0.5–6.4) year. Mean annualized relapse rate significantly decreased from 0.8 during last immunosuppressive DMT to 0.18 after rituximab (p < 0.0001). While 72% of patients showed gadolinium-enhancing lesions on the last MRI performed during last immunosuppressive DMT, 8% of them showed gadolinium-enhancing lesions on the first MRI performed 6.1 (range 1.4–18.4) months after rituximab (p < 0.0001).
Conclusion:
This study provides level IV evidence that rituximab reduces clinical and MRI disease activity in patients with active RRMS despite immunosuppressive DMT.
Background:
A paradoxical discrepancy between severe peripapillary retinal nerve fiber layer (pRNFL) atrophy and good visual outcome had been reported in patients with myelin oligodendrocyte ...glycoprotein-immunoglobulin G (MOG-IgG)-associated optic neuritis (ON). However, only visual acuity (VA) was assessed.
Objectives:
To study visual field (VF) outcomes of patients with MOG-IgG-associated ON and evaluate the correlation between functional eye outcome and retinal structural changes assessed by optical coherence tomography.
Methods:
The records of 32 patients with MOG-IgG-associated ON who underwent ophthalmological examination at least 12 months after ON onset were reviewed. Degree of VF disability was determined by mean deviation (MD).
Results:
At final assessment (median, 35 months), 4.2% of 48 affected eyes (AE) had VA ⩽ 0.1, 40% had abnormal MD, and among AE with final VA ⩾ 1.0, 31% had mild to moderate damage. Thinning of the inner retinal layers was significantly correlated with MD impairment. Analysis demonstrated a threshold of pRNFL thickness (50 µm), below which MD was significantly worse (mean, −2.27 dB vs −17.72 dB; p = 0.0003). ON relapse was significantly associated with poor visual outcome assessed by MD.
Conclusion:
Functional impairment measured with VF is not rare, and MD assessment better reflects actual structural damage.
Background:
Yellow fever vaccine (YFV) is not advised for multiple sclerosis (MS) patients because of the potential risk of post-vaccine relapses.
Objective:
To assess the risk of relapsing-remitting ...multiple sclerosis (RR-MS) worsening after YFV.
Methods:
Non-interventional observational retrospective, exposed/non-exposed cohort study nested in the French national cohort including MS.
Results:
128 RR-MS were included. The 1-year annualized relapse rate (ARR) following YFV did not differ between exposed: 0.219 (0.420) and non-exposed subjects: 0.208 (0.521) (p = 0.92). Time to first relapse was not different between groups (adjusted hazard ratio (HR) = 1.33; 95% confidence interval (CI) = 0.53–3.30, p = 0.54).
Conclusion:
These results suggest that YFV does not worsen the course of RR-MS.
Background:
Epidemiologic studies on coronavirus disease 2019 (COVID-19) in patients with multiple sclerosis (pwMS) have focused on the first waves of the pandemic until early 2021.
Objectives:
We ...aimed to extend these data from the onset of the pandemic to the global coverage by vaccination in summer 2022.
Methods:
This retrospective, multicenter observational study analyzed COVISEP registry data on reported COVID-19 cases in pwMS between January 2020 and July 2022. Severe COVID-19 was defined as hospitalization or higher severity.
Results:
Among 2584 pwMS with confirmed/highly suspected COVID-19, severe infection rates declined from 14.6% preomicron wave to 5.7% during omicron wave (p < 0.001). Multivariate analysis identified age (odds ratio (OR) = 1.43, 95% confidence interval (CI) = 1.25–1.64 per 10 years), male sex (OR = 2.01, 95% CI = 1.51–2.67), obesity (OR = 2.36, 95% CI = 1.52–3.68), cardiac comorbidities (OR = 2.36, 95% CI = 1.46–3.83), higher Expanded Disability Status Scale (EDSS) scores (OR = 2.09, 95% CI = 1.43–3.06 for EDSS 3–5.5 and OR = 4.53, 95% CI = 3.04–6.75 for EDSS ⩾6), and anti-CD20 therapies (OR = 2.67, 95% CI = 1.85–3.87) as risk factors for COVID-19 severity. Vaccinated individuals experienced less severe COVID-19, whether on (risk ratio (RR) = 0.64, 95% CI = 0.60–0.69) or off (RR = 0.32, 95% CI = 0.30–0.33) anti-CD20.
Discussion:
In pwMS, consistent risk factors were anti-CD20 therapies and neurological disability, emerging as vital drivers of COVID-19 severity regardless of wave, period, or vaccination status.
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.
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.
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.
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.
Background:
Vaccination in patients with multiple sclerosis (MS) treated with immunosuppressive drugs is highly recommended. Regarding COVID-19 vaccination, no specific concern has been raised.
...Objectives:
We aimed to evaluate if COVID-19 vaccination or infection increased the risk of disease activity, either radiological or clinical, with conversion to MS in a cohort of people with a radiologically isolated syndrome (RIS).
Methods:
This multicentric observational study analyzed patients in the RIS Consortium cohort during the pandemic between January 2020 and December 2022. We compared the occurrence of disease activity in patients according to their vaccination status. The same analysis was conducted by comparing patients’ history of COVID-19 infection.
Results:
No difference was found concerning clinical conversion to MS in the vaccinated versus unvaccinated group (6.7% vs 8.5%, p > 0.9). The rate of disease activity was not statistically different (13.6% and 7.4%, respectively, p = 0.54). The clinical conversion rate to MS was not significantly different in patients with a documented COVID-19 infection versus non-infected patients.
Conclusion:
Our study suggests that COVID-19 infection or immunization in RIS individuals does not increase the risk of disease activity. Our results support that COVID-19 vaccination can be safely proposed and repeated for these subjects.
The treatment strategy in relapsing multiple sclerosis (RMS) is a complex decision requiring individualization of treatment sequences to maximize clinical outcomes. Current local and international ...guidelines do not provide specific recommendation on the use of immune reconstitution therapy (IRT) as alternative to continuous immunosuppression in the management of RMS. The objective of the program was to provide consensus-based expert opinion on the optimal use of IRT in the management of RMS. A Delphi method was performed from May 2022 to July 2022. Nineteen clinical assertions were developed by a scientific committee and sent to 14 French clinical experts in MS alongside published literature. Two consecutive reproducible anonymous votes were conducted. Consensus on recommendations was achieved when more than 75% of the respondents agreed or disagreed with the clinical assertions. After the second round, consensus was achieved amongst 16 out of 19 propositions: 13 clinical assertions had a 100% consensus, 3 clinical assertions a consensus above 75% and 3 without consensus. Expert-agreed consensus is provided on topics related to the benefit of the early use of IRT from immunological and clinical perspectives, profiles of patients who may benefit most from the IRT strategy (e.g. patients with family planning, patient preference and lifestyle requirements). These French expert consensuses provide up-to-date relevant guidance on the use of IRT in clinical practice. The current program reflects status of knowledge in 2022 and should be updated in timely manner when further clinical data in IRT become available.
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