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The prevalence of multiple sclerosis in the south of Europe seems to be higher than previously considered. This study aimed to probe a possible increase in the prevalence of multiple sclerosis (MS) in Osona over the past 17 years. This was a cross-sectional study including MS-confirmed cases from several sources of information. Crude and adjusted prevalence rates were obtained. One hundred and twenty patients fulfilled the study criteria. The crude prevalence of MS was 79.9 (95% CI: 66.3–95.6) per 100,000 inhabitants and 91.2 (95% CI: 75.5–109.2) per 100,000 among Spanish born individuals. The prevalence of multiple sclerosis cases in Osona has increased over the past 17 years to being one of the highest reported in Spain. [ABSTRACT FROM PUBLISHER]

Background: Prior studies have reported lower effectiveness of XBB.1.5-adapted vaccines against hospitalization related to the Omicron JN.1 variant than the XBB variant. This study evaluated the effectiveness and durability of the BNT162b2 XBB.1.5-adapted vaccine against JN.1-related hospitalization during the 2023-2024 season in Europe., Methods: A test-negative case-control study was carried out in adults (≥18 y) hospitalized between 2 October 2023 and 2 April 2024 with severe acute respiratory infection (SARI) within the id.DRIVE partnership. This study included nine sites across Belgium, Germany, Italy, and Spain. Cases had a laboratory-confirmed JN.1 infection or a positive SARS-CoV-2 test with symptom onset during JN.1 predominance; controls had a negative SARS-CoV-2 test and symptom onset during JN.1 predominance. The primary objective was to estimate BNT162b2 XBB.1.5-adapted vaccine effectiveness (VE) against COVID-19 hospitalization. One case was matched with up to four controls, according to symptom onset date and site. Multivariable analyses were adjusted for symptom onset date, age, sex, and number of chronic conditions., Findings: Among 308 test-positive cases and 1117 test-negative controls, BNT162b2 XBB.1.5-adapted VE against hospitalization compared to no vaccination this season was 53.8% (95% CI 38.4-65.4) after a median of 63 days following vaccination. Protection was sustained through five months; VE was 52.2% (95% CI 41.3-61.1) 2 to <4 weeks after vaccination, 48.9% (95% CI 17.9-68.2) at 4 to <8 weeks, and ranged from 54.6% to 59.5% at 4-week intervals from 8 to <22 weeks., Interpretation: BNT162b2 XBB.1.5-adapted vaccine provided protection against JN.1-related hospitalization, regardless of prior vaccination history, with no evidence of waning through five months. These data support yearly vaccination against COVID-19 to prevent severe illness during the respiratory virus season., Funding: Pfizer., Competing Interests: All authors have completed the ICMJE disclosure form and declare: Pfizer Inc. funded this study. C Marques, HRV, JLN, JMML, JY, MMu, LJ, and SV are employees of Pfizer Inc. HRV, JLN, JMML, JY, MMu, LJ, and SV hold stocks or stock options in Pfizer Inc. EC-S, KB, LD, LdM, MMi, and TMPT are employees of P95 Epidemiology & Pharmacovigilance, a company providing scientific services in the field of vaccines. KB and TMPT declare stock or stock options in P95. KB has received consulting fees from Pfizer Inc. for conducting this study, royalties for the book ‘Vaccination Programmes: epidemiology, monitoring, evaluation’ by Hahné, Bollaerts, Farrington, and consulting fees from AstraZeneca, Bavarian Nordic, CureVac, Janssen, GSK, Pfizer, Novavax, Valneva, and the World Health Organization. AOS reports that Pfizer partially funded the hospital network for the collection of data via id.DRIVE. IC reports support from Pfizer for congress attendance. AM-I reports being a co-principal investigator from VAHNSI (Fisabio). Fisabio received funding from P95 via id.DRIVE to conduct the study. BG and GI declare payment from the id.DRIVE Consortium to their institutions for conducting the study. BG further declares that data collaboration between P95 and Pfizer is reported. GI has received grants or contracts, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, support for attending meetings and/or travel, and declares participation on a Data Safety Monitoring Board (DSMB) or Advisory Board from GSK, MSD, Sanofi, Pfizer, Seqirus, Moderna, AstraZeneca, Viatris, and Novavax. GR declares payments to his institution by the CAPNETZ foundation, of whose executive board he is the chairman. Furthermore, GR reports personal fees from Astra Zeneca, Atriva, Boehringer Ingelheim, GSK, Insmed, MSD, Sanofi, Novartis, and Pfizer for consultancy during advisory board meetings and personal fees from AstraZeneca, Berlin Chemie, BMS, Boehringer Ingelheim, Chiesi, Essex Pharma, Grifols, GSK, Insmed, MSD, Roche, Sanofi, Solvay, Takeda, Novartis, Pfizer, and Vertex for lectures. SO-R declares payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from GSK and Sanofi. AÁ, C Martin, EC-S, GLtK, LdM, LD and MMI declare no conflicts of interest., (© 2024 The Authors.)

Background: Organizing pneumonia (OP), an interstitial lung disease, has been observed in patients with inflammatory demyelinating diseases (IDDs) treated with anti-CD20, particularly after COVID-19, but data are limited., Aim: To provide a detailed characterization of COVID-19-associated OP in IDD patients treated with anti-CD20., Methods: Bi-centric retrospective cohort study including patients with multiple sclerosis (MS), aquaporin-4-positive neuromyelitis optica spectrum disorder (AQP4 + NMOSD), and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) who received anti-CD20 and were diagnosed with COVID-19-associated OP between March 2020 and October 2023., Results: Nineteen patients were included (mean age 46.8 years; 52.6% female; 63% rituximab, 37% ocrelizumab). Sixteen had MS, two MOGAD, and one AQP4 + NMOSD. Intermittent fever was the predominant symptom. Hospitalization occurred in all but one patient, without fatalities. Chest CT consistently showed OP patterns. Thirteen patients had positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR in bronchoalveolar lavage. Treatments included corticosteroids, antivirals, monoclonal antibodies, and convalescent plasma. Fourteen patients postponed infusions; nine resumed post-recovery (median 11.9 months), two switched due to hypogammaglobulinemia, and three stopped. After a mean follow-up of 1.5 years, lung abnormalities and clinical manifestations resolved in 18 patients; however, 13 experienced long-COVID., Conclusions: In anti-CD20-treated patients with recurrent fever and distinctive CT features, COVID-19-associated OP should be considered., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: R Carvajal is currently being funded by a Research grand from the European Charcot Foundation. In 2023, he received a grant by “Vall d′Hebron Institut de Recerca.” In 2021, he received an ECTRIMS Fellowship training performed during 2021–2022. He has also received speaking honoraria from Roche, Novartis, Biogen, Merck, and Sanofi.B Rodríguez-Acevedo has received speaking honoraria from Merck and honoraria for consulting services from Novartis.L García-Vasco has received honoraria as a speaker from Merck and Novartis; and received support for attending meetings and congresses from BMS, Horizon, Janssen, Novartis and Sanofi.A Zabalza has a predoctoral grant Rio Hortega, from the Instituto de Salud CarlosIII, Spain (CM22/00237), received travel expenses for scientific meetings from Biogen-Idec, Merck Serono and Novartis; speaking honoraria from Eisai; and a study grant from Novartis.H Ariño has received grant from Instituto de Salud Carlos III, Spain; JR22/00072.L Bollo is supported by a 1-year stipend endowed by the NMSS/AAN John Dystel Prize for Multiple Sclerosis Research awarded to Prof. Xavier Montalban in 2022.N Cabello-Clotet has received support for attending meetings and congresses and honoraria as a speaker from Gilead, GSK Janssen, and MSD.A Cobo-Calvo has received grant from Instituto de Salud Carlos III, Spain; JR19/00007.M Comabella has received compensation for consulting services and speaking honoraria from Bayer Schering Pharma, Merck Serono, Biogen-Idec, Teva Pharmaceuticals, Sanofi-Aventis, Genzyme, and Novartis.A García-Sarreón is currently an ECTRIMS clinical fellowship awardee for 2023–2024 and receives support from ECTRIMS.S Otero-Romero has received speaking and consulting honoraria from Genzyme, Biogen-Idec, Novartis, Roche, Excemed and MSD; as well as research support from Novartis.A Pappolla has received funding travel from Roche and speaking honoraria from Novartis. He performed an ECTRIMS Clinical Training Fellowship program during 2021, and is currently performing an MSIF-ARSEP Fellowship program.J Rio has received speaking honoraria and personal compensation for participating on Advisory Boards from Biogen-Idec, Genzyme, Janssen, Merck- Serono, Novartis, Teva, Roche, and Sanofi-Aventis.P Tagliani has received support during one year as an ECTRIMS clinical fellowship awardee in 2019–2020.C Tur is currently being funded by a Miguel Servet contract, awarded by the Instituto de Salud Carlos III (ISCIII), Ministerio de Ciencia e Innovación de España (CP23/00117). She has also received a 2020 Junior Leader La Caixa Fellowship (fellowship code: LCF/BQ/PI20/11760008), awarded by “la Caixa” Foundation (ID 100010434), a 2021 Merck’s Award for the Investigation in MS awarded by Fundación Merck Salud (Spain), a 2021 Research Grant (PI21/01860) awarded by the ISCIII, Ministerio de Ciencia e Innovación de España, and a FORTALECE research grant (FORT23/00034) also by the ISCIII, Ministerio de Ciencia e Innovación de España. In 2015, she received an ECTRIMS Post-doctoral Research Fellowship and has received funding from the UK MS Society. She is a member of the Editorial Board of Neurology Journal and Multiple Sclerosis Journal. She has also received honoraria from Roche, Novartis, Merck, Immunic Therapeutics, and Bristol Myers Squibb. She is a steering committee member of the O’HAND trial and of the Consensus group on Follow-on DMTs.A Vidal-Jordana has received support has received support for contracts Juan Rodes (JR16/00024) and from Fondo de Investigación en Salud (PI17/02162 and PI22/01589) from Instituto de Salud Carlos III, Spain, and has engaged in consulting and/or participated as speaker in events organized by Roche, Novartis, and Merck.A Vilaseca has received a Rio Hortega grant (CM22/00247) by Institute of Health Carlos III (ISCIII).A Villar has engaged in consulting and/or participated as a speaker in events organized by Boehringer Ingelheim, Roche, Janssen, and Glaxo, with travel expenses covered by Boehringer Ingelheim, Roche, Glaxo, Chiesi, and Novartis for participation in scientific meetings. In addition, research support has been received from Janssen and GlaxoSmithKline.J Sastre-Garriga serves as co-Editor for Europe on the editorial board of Multiple Sclerosis Journal and as Editor-in-Chief in Revista de Neurología, receives research support from Fondo de Investigaciones Sanitarias (19/950) and has served as a consultant/speaker for Biogen, Celgene/Bristol Meyers Squibb, Sanofi, Novartis and Merck.C Oreja-Guevara has received honoraria for speaking and serving on advisory boards from Biogen Idec., F. Hoffmann-La Roche Ltd, Sanofi-Genzyme, Merck, Janssen, BMS, Novartis and Teva.M Tintoré has received compensation for consulting services, speaking honoraria and research support from Almirall, Bayer Schering Pharma, Biogen-Idec, Genzyme, Immunic Therapeutics, Janssen, Merck-Serono, Novartis, Roche, Sanofi-Aventis, Viela Bioand Teva Pharmaceuticals. Data Safety Monitoring Board for Parexel and UCB Biopharma, Relapse Adjudication Committee for IMCYSE SA.X Montalban has received speaking honoraria and travel expenses for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Abbvie, Actelion, Alexion, Biogen, Bristol-Myers Squibb/Celgene, EMD Serono, Genzyme, Hoffmann-La Roche, Immunic, Janssen Pharmaceuticals, Medday, Merck, Mylan, Nervgen, Novartis, Sandoz, Sanofi-Genzyme, Teva Pharmaceutical, TG Therapeutics, Excemed, MSIF and NMSS.G Arrambide has received speaking honoraria and consulting services or participation in advisory boards from Sanofi, Roche and Horizon Therapeutics/Amgen; and travel expenses for scientific meetings from Novartis, Roche, ECTRIMS and EAN.J Castillo, A Falcó-Roget, I Galan, I Gómez-Estévez, G Granados, G Mato-Chain, D La Puma, L Midaglia, A Nieto-García, M Rodríguez, and I Sansano report no disclosures.

Importance: Vaccination in patients with highly active multiple sclerosis (MS) requiring prompt treatment initiation may result in impaired vaccine responses and/or treatment delay., Objective: To assess the immunogenicity and safety of inactivated vaccines administered during natalizumab treatment., Design, Setting, and Participants: This self-controlled, prospective cohort study followed adult patients with MS from 1 study center in Spain from September 2016 to February 2022. Eligible participants included adults with MS who completed immunization for hepatitis B virus (HBV), hepatitis A virus (HAV), and COVID-19 during natalizumab therapy. Data analysis was conducted from November 2022 to February 2023., Exposures: Patients were categorized according to their time receiving natalizumab treatment at the time of vaccine administration as short-term (≤1 year) or long-term (>1 year)., Main Outcomes and Measures: Demographic, clinical, and radiological characteristics were collected during the year before vaccination (prevaccination period) and the year after vaccination (postvaccination period). Seroprotection rates and postvaccination immunoglobulin G titers were determined for each vaccine within both periods. Additionally, differences in annualized relapse rate (ARR), new T2 lesions (NT2L), Expanded Disability Status Scale (EDSS) scores, and John Cunningham virus (JCV) serostatus between the 2 periods were assessed., Results: Sixty patients with MS (mean [SD] age, 43.2 [9.4] years; 44 female [73.3%]; 16 male [26.7%]; mean [SD] disease duration, 17.0 [8.7] years) completed HBV, HAV, and mRNA COVID-19 immunization during natalizumab treatment, with 12 patients in the short-term group and 48 patients in the long-term group. The global seroprotection rate was 93% (95% CI, 86%-98%), with individual vaccine rates of 92% for HAV (95% CI, 73%-99%), 93% for HBV (95% CI, 76%-99%), and 100% for the COVID-19 messenger RNA vaccine (95% CI, 84%-100%). Between the prevaccination and postvaccination periods there was a significant reduction in the mean (SD) ARR (0.28 [0.66] vs 0.01 [0.12]; P = .004) and median (IQR) NT2L (5.00 [2.00-10.00] vs 0.81 [0.00-0.50]; P = .01). No changes in disability accumulation were detected (median [IQR] EDSS score 3.5 [2.0-6.0] vs 3.5 [2.0-6.0]; P = .62). No differences in safety and immunogenicity were observed for all vaccines concerning the duration of natalizumab treatment., Conclusions and Relevance: The findings of this cohort study suggest that immunization with inactivated vaccines during natalizumab therapy was both safe and immunogenic, regardless of the treatment duration. Natalizumab may be a valuable option for proper immunization, averting treatment delays in patients with highly active MS; however, this strategy needs to be formally evaluated.

Introduction: Prospective data on the risk of hepatitis B reactivation (HBVr) among patients with resolved HBV infection undergoing anti-CD20 antibodies monotherapy is scarce. We aimed to assess the risk of HBVr in patients with resolved HBV infection treated with rituximab or ocrelizumab in monotherapy for multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD) without antiviral prophylaxis., Methods: HEBEM is a prospective study that included all consecutive adults HBsAg-negative/anti-HBc-positive who initiated anti-CD20 antibodies for MS or NMOSD at Cemcat. Inclusion criteria encompassed undetectable HBV-DNA, absence of other immunosuppressants or antiviral therapy. Every 6 months HBsAg, ALT and HBV-DNA were performed to rule out HBVr (defined by 2-log increase in HBV-DNA or seroconversion to HBsAg+)., Results: From August/2019 to August/2022, 540 subjects initiated anti-CD20 antibodies, 28 (5.2%) were anti-HBc-positive and were included. Twenty-two received rituximab and 6 ocrelizumab. The majority (89.3%) had previously received ≥ 1 immunomodulatory drug, with corticosteroids (82.1%) and interferon (42.9%) as the most common. At inclusion, all presented normal transaminases and undetectable HBV-DNA. Median anti-HBs levels were 105.5 mIU/mL (IQR 0-609). Median follow-up was 3.1 years (2.1-4.0). Median number of cycles of anti-CD20 antibodies was 6 (3-7), with a cumulative dose of 8.5 g (5.8-11.2) of rituximab and 3 g (1.8-3.8) of ocrelizumab. Neither cases of HBVr nor changes in anti-HBs titers were observed per 83.6 patient-years treated with monotherapy with anti-CD20 antibodies., Conclusions: In this cohort of patients with MS or NMOSD and resolved HBV infection, anti-CD20 monotherapy was not associated with detectable risk of HBV reactivation despite the lack of antiviral prophylaxis., (© 2023. The Author(s).)

Background: Mumps-Measles-Rubella (MMR) and Varicella zoster vaccines (VAR) are live attenuated vaccines, usually administered in a two-dose scheme at least 4 weeks apart. However, single-dose immunization schemes may also be effective and can reduce delays in immunosuppressive treatment initiation in patients with multiple sclerosis (pwMS) who need to be immunized., Objectives: To evaluate the immunogenicity of a single-dose attempt (SDA) versus the standard immunization scheme (SIS) with VAR and/or MMR in pwMS., Methods: Retrospective observational study in pwMS vaccinated against VAR and/or MMR. We compared seroprotection rates and antibody geometric mean titers (GMTs) between the two strategies., Results: Ninety-six patients were included. Thirty-one patients received VAR and 67 MMR. In the SDA group, the seroprotection rate was 66.7% (95% confidence interval (CI): 53.3-78.3) versus 97.2% (95% CI: 85.5-99.9) in the SIS ( p  < 0.001). For the seroprotected patients, GMTs were similar for both schemes., Conclusion: An SDA of VAR and/or MMR vaccines could be sufficient to protect almost two-thirds of patients. Testing immunogenicity after a single dose of VZ and/or MMR could be included in routine clinical practice to achieve rapid immunization., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: R. Carvajal is currently being funded by ‘Vall d’Hebron Institut de Recerca’ grand, this project was supported by ECTRIMS Fellowship training performed during 2021–2022, he has also received speaking honoraria and personal compensation for participating on Advisory Boards and from Roche, Novartis, BIIB-Colombia, Merck, and Sanofi. C. Tur is currently being funded by a Junior Leader La Caixa Fellowship (fellowship code is LCF/BQ/PI20/11760008), awarded by ‘la Caixa’ Foundation (ID 100010434), she has also received the 2021 Merck’s Award for the Investigation in MS, awarded by Fundación Merck Salud (Spain) and a grant awarded by the Instituto de Salud Carlos III (ISCIII), Ministerio de Ciencia e Innovación de España (PI21/01860); in 2015, she received an ECTRIMS Post-doctoral Research Fellowship and has received funding from the UK MS Society, she is a member of the Editorial Board of Neurology and Multiple Sclerosis Journal, she has also received honoraria from Roche and Novartis and is a steering committee member of the O’HAND trial and of the Consensus group. X. Martínez-Gómez has received research support fees from GlaxoSmithKline, Sanofi Pasteur MSD, Statens Serum Institut & Janssen Vaccine, as well as travel expenses fees from GlaxoSmithKline and Sanofi Pasteur MS. L. Bollo is supported by a 1-year stipend endowed by the NMSS/AAN John Dystel Prize for Multiple Sclerosis Research awarded to Prof. Xavier Montalban in 2022. J. Esperalba reports no disclosures. M. Rodríguez reports no disclosures. A. Pappolla has received funding travel from Roche and speaking honoraria from Novartis. He developed this project during a 2021 ECTRIMS Clinical Training Fellowship programme, and is currently performing an MSIF-ARSEP Fellowship programme. A. Cobo-Calvo has received a grant from Instituto de Salud Carlos III, Spain; JR19/00007. P. Carbonell yearly salary is supported by a grant from Biogen to Fundació privada Cemcat for statistical analysis. B. Borras-Bermejo has received travel expenses for scientific meetings from GlaxoSmithKline J. Rio has received speaking honoraria and personal compensation for participating on Advisory Boards from Biogen-Idec, Genzyme, Janssen, Merck-Serono, Novartis, Teva, Roche, and Sanofi-Aventis. J. Castilló reports no disclosures. N. Braga has received travel expenses for scientific meetings and speaking honoraria from Roche, Novartis, Biogen, Merck and was funded by ECTRIMS Fellowship in 2022–2023. N. Mongay-Ochoa has a predoctoral grant Rio Hortega, from the Instituto de Salud Carlos III (CM21/00018), she also has received speaking honoraria and travel expenses from Merck and Roche. J.A. Rodigo-Pendás has received research support fees from GlaxoSmithKline, Sanofi Pasteur MSD, Statens Serum Institut, Janssen Vaccines & Prevention B.V. and Spanish Clinical Research Network—SCReN and travel expenses fees from Sanofi Pasteur MSD. A. Vidal-Jordana has engaged in consulting and/or participated as speaker in events organized by Roche, Novartis, Merck, and Sanofi. G. Arrambide has received speaking honoraria and consulting services or participation in advisory boards from Sanofi, Merck, Roche, and Horizon Therapeutics; travel expenses for scientific meetings from Novartis, Roche, and ECTRIMS. I. Galán reports no disclosures. B. Rodríguez-Acevedo has received speaking honoraria from Merck and honoraria for consulting services from Novartis. A. Zabalza has a predoctoral grant Rio Hortega, from the Instituto de Salud Carlos III, Spain (CM22/00237), received travel expenses for scientific meetings from Biogen-Idec, Merck Serono and Novartis, speaking honoraria from Eisai and a study grant from Novartis. L. Midaglia reports no disclosures. M. Comabella has received compensation for consulting services and speaking honoraria from Bayer Schering Pharma, Merck Serono, Biogen-Idec, Teva Pharmaceuticals, Sanofi-Aventis, Genzyme, and Novartis. J. Sastre-Garriga serves as co-Editor for Europe on the editorial board of Multiple Sclerosis Journal and as Editor-in-Chief in Revista de Neurología, receives research support from Fondo de Investigaciones Sanitarias (19/950) and has served as a consultant/speaker for Biogen, Celgene/Bristol Meyers Squibb, Sanofi, Novartis and Merck. X. Montalbán has received speaking honoraria and travel expenses for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Abbvie, Actelion, Alexion, Biogen, Bristol-Myers Squibb/Celgene, EMD Serono, Genzyme, Hoffmann-La Roche, Immunic, Janssen Pharmaceuticals, Medday, Merck, Mylan, Nervgen, Novartis, Sandoz, Sanofi-Genzyme, Teva Pharmaceutical, TG Therapeutics, Excemed, MSIF, and NMSS. M. Tintore has received compensation for consulting services, speaking honoraria and research support from Almirall, Bayer Schering Pharma, Biogen-Idec, Genzyme, Janssen, Merck-Serono, Novartis, Roche, Sanofi-Aventis, Viela Bio and Teva Pharmaceuticals. Data Safety Monitoring Board for Parexel and UCB Biopharma. S. Otero-Romero has received speaking and consulting honoraria from Genzyme, Biogen-Idec, Novartis, Roche, Excemed, and MSD; as well as research support from Novartis.

Background and Objectives: Early treatment is associated with better long-term outcomes in patients with a first demyelinating event and early multiple sclerosis (MS). However, magnetic resonance (MR) findings are not usually integrated to construct propensity scores (PSs) when evaluating outcomes. We assessed the association of receiving very early treatment with the risk of long-term disability including an MR score (MRS) in patients with a first demyelinating event., Methods: We included 580 patients with a first demyelinating event prospectively collected between 1994 and 2021, who received at least 1 disease-modifying drug (DMD). Patients were classified into tertiles according to the cohort's distribution of the time from the first demyelinating event to the first DMD: first tertile (FT) or very early treatment (6 months; n = 194), second tertile (6.1-16 months, n = 192), and third tertile (TT) (16.1 months, n = 194). A 5-point MRS was built according to the sum of the following indicators: ≥9 brain lesions (1 point); ≥1 infratentorial lesion (1 point); ≥1 spinal cord (SC) lesion (1 point); ≥1 contrast-enhancing (CE) brain lesion (1 point); and ≥1 CE SC lesion (1 point). PS based on covariates and the MRS was computed for each of the outcomes. Inverse PS-weighted Cox and linear regression models assessed the risk of different outcomes between tertile groups. Finally, to confirm the role of MR in treatment decision, we studied the time elapsed from the first demyelinating event to treatment initiation according to the MRS in all patients with radiologic available information, renamed as raw-MRS., Results: Very early treatment decreased the risk of reaching Expanded Disability Status Scale 3.0 (hazard ratio [HR] 0.55, 95% CI 0.32-0.97), secondary progressive MS (HR 0.40, 95% CI 0.19-0.85), and sustained disease progression at 12 months after treatment initiation (HR 0.50, 95% CI 0.29-0.84), when compared with patients from the TT group. Patients from the FT group had a lower disability progression rate (β estimate -0.009, 95% CI -0.016 to -0.002) and a lower severe disability measured by the Patient-Determined Disease Step (β estimate -0.52, 95% CI -0.91 to -0.13) than the TT group. Finally, there was a 62.4% reduction in the median time between the first demyelinating event and the first-ever treatment initiation from patients displaying a raw-MRS 1 to patients with a raw-MRS 5., Discussion: Using PS models with and without MRS, we showed that treatment initiation at very early stages is associated with a reduction in the risk of long-term disability accrual in patients with a first demyelinating event., Classification of Evidence: This study provides Class III evidence that earlier treatment of patients with MS presenting with a first demyelinating event is associated with improved clinical outcomes., (© 2023 American Academy of Neurology.)

Background: Vaccination is considered the most effective measure for preventing influenza and its complications. The influenza vaccine effectiveness (IVE) varies annually due to the evolution of influenza viruses and the update of vaccine composition. Assessing the IVE is crucial to facilitate decision making in public health policies., Aim: to estimate the IVE against hospitalization and its determinants in the 2021/22 season in a Spanish tertiary hospital., Methods: We conducted a prospective observational test-negative design study within the Development of Robust and Innovative Vaccine Effectiveness (DRIVE) project. Hospitalized patients with severe acute respiratory infection (SARI) and an available influenza reverse transcription polymerase chain reaction (RT-PCR) were selected and classified as cases (positive influenza RT-PCR) or controls (negative influenza RT-PCR). Vaccine information was obtained from electronic clinical records shared by public healthcare providers. Information about potential confounders was obtained from hospital clinical registries. The IVE was calculated by subtracting the ratio of the odds of vaccination in cases and controls from one, as a percentage (IVE = (1 - odds ratio (OR)) × 100). Multivariate IVE estimates were calculated using logistic regression., Results: In total, 260 severe acute respiratory infections (SARI) were identified, of which 34 were positive for influenza, and all were subtype A(H3N2). Fifty-three percent were vaccinated. Adjusted IVE against hospitalization was 26.4% (95% CI -69% to 112%). IVE determinants could not be explored due to sample size limitations., Conclusion: Our data revealed non-significant moderate vaccine effectiveness against hospitalization for the 2021/2022 season.

Background and Purpose: With the new highly active drugs available for people with multiple sclerosis (pwMS), vaccination becomes an essential part of the risk management strategy. We aimed to develop a European evidence-based consensus for the vaccination strategy of pwMS who are candidates for disease-modifying therapies (DMTs)., Methods: This work was conducted by a multidisciplinary working group using formal consensus methodology. Clinical questions (defined as population, interventions and outcomes) considered all authorized DMTs and vaccines. A systematic literature search was conducted and quality of evidence was defined according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. The recommendations were formulated based on the quality of evidence and the risk-benefit balance., Results: Seven questions, encompassing vaccine safety, vaccine effectiveness, global vaccination strategy and vaccination in subpopulations (pediatric, pregnant women, elderly and international travelers) were considered. A narrative description of the evidence considering published studies, guidelines and position statements is presented. A total of 53 recommendations were agreed by the working group after three rounds of consensus., Conclusion: This first European consensus on vaccination in pwMS proposes the best vaccination strategy according to current evidence and expert knowledge, with the goal of homogenizing the immunization practices in pwMS., (© 2023 The Authors. Co-published by European Academy of Neurology and European Committee of Treatment of Research in Multiple Sclerosis.)

Background: With the new highly active drugs available for people with multiple sclerosis (pwMS), vaccination becomes an essential part of the risk management strategy., Objective: To develop a European evidence-based consensus for the vaccination strategy of pwMS who are candidates for disease-modifying therapies (DMTs)., Methods: This work was conducted by a multidisciplinary working group using formal consensus methodology. Clinical questions (defined as population, interventions, and outcomes) considered all authorized DMTs and vaccines. A systematic literature search was conducted and quality of evidence was defined according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. The recommendations were formulated based on the quality of evidence and the risk-benefit balance., Results: Seven questions, encompassing vaccine safety, vaccine effectiveness, global vaccination strategy and vaccination in sub-populations (pediatric, pregnant women, elderly and international travelers) were considered. A narrative description of the evidence considering published studies, guidelines, and position statements is presented. A total of 53 recommendations were agreed by the working group after three rounds of consensus., Conclusion: This first European consensus on vaccination in pwMS proposes the best vaccination strategy according to current evidence and expert knowledge, with the goal of homogenizing the immunization practices in pwMS.

Background: Vaccine effectiveness (VE) studies with long-term follow-up are needed to understand durability of protection against severe COVID-19 outcomes conferred by primary-series vaccination in individuals not receiving boosters. COVIDRIVE is a European public-private partnership evaluating brand-specific vaccine effectiveness (VE). We report a prespecified interim analysis of primary-series AZD1222 (ChAdOx1 nCoV-19) VE., Methods: Seven Study Contributors in Europe collected data on individuals aged ≥18 years who were hospitalised with severe acute respiratory infection (June 1st, 2021-September 5th, 2022) and eligible for COVID-19 vaccination prior to hospitalisation. In this test-negative case-control study, individuals were defined as test-positive cases or test-negative controls (SARS-CoV-2 RT-PCR) and were either fully vaccinated (two AZD1222 doses, 4-12 weeks apart, completed ≥14 days prior to symptom onset; no booster doses) or unvaccinated (no COVID-19 vaccine prior to hospitalisation). The primary objective was to estimate AZD1222 VE against COVID-19 hospitalisation. A literature review and meta-regression were conducted to contextualise findings on durability of protection., Findings: 761 individuals were included during the 15-month analysis period. Overall AZD1222 VE estimate was 72.8% (95% CI, 53.4-84.1). VE was 93.8% (48.6-99.3) in participants who received second AZD1222 doses ≤8 weeks prior to hospitalisation, with spline-based VE estimates demonstrating protection (VE ≥ 50%) 30 weeks post-second dose. Meta-regression analysis (data from seven publications) showed consistent results, with ≥80% protection against COVID-19 hospitalisation through ∼43 weeks post-second dose, with some degree of waning., Interpretation: Primary-series AZD1222 vaccination confers protection against COVID-19 hospitalisation with enduring levels of VE through ≥6 months., Funding: AstraZeneca., Competing Interests: WM, CMG, MO, and ST declare employment by AstraZeneca and ownership of AstraZeneca stocks/shares. LdM, AD, CW-T, WH-M, LD, GR, ALS, TYCN, and KB declare employment by P95. ALS and TYCN were contracted to AstraZeneca at the time of this work. P95 received consulting fees from several COVID-19 vaccine manufacturers, including AstraZeneca, for the COVIDRIVE study. AC declares funding from COVIDRIVE industry partners (AstraZeneca, Janssen, Moderna, Novavax, CureVac, Sanofi, Valneva, GlaxoSmithKline, Bavarian Nordic) for the COVIDRIVE consortium, of which FISABIO is the coordinator, and honoraria for lectures and educational events from GlaxoSmithKline and for presentations from MSD and HIPRA. GM declares no conflicts of interest related to this analysis, and honoraria from GlaxoSmithKline associated with herpes virus vaccine. AM-I declares funding from COVIDRIVE industry partners (AstraZeneca, Janssen, Moderna, Novavax, CureVac, Sanofi, Valneva, GlaxoSmithKline, Bavarian Nordic) for the COVIDRIVE consortium, of which FISABIO is the coordinator, and honoraria for educational events from MSD and for presentations from Sanofi Pasteur. GI declares no conflicts of interest. SO-R declares payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from EXCEMED and Sanofi. SB declares speaker honorarium from GlaxoSmithKline. CM declares advisory board participation for AstraZeneca in 2021., (© 2023 The Author(s).)

Importance: Progression independent of relapse activity (PIRA) is the main event responsible for irreversible disability accumulation in relapsing multiple sclerosis (MS)., Objective: To investigate clinical and neuroimaging predictors of PIRA at the time of the first demyelinating attack and factors associated with long-term clinical outcomes of people who present with PIRA., Design, Setting, and Participants: This cohort study, conducted from January 1, 1994, to July 31, 2021, included patients with a first demyelinating attack from multiple sclerosis; patients were recruited from 1 study center in Spain. Patients were excluded if they refused to participate, had alternative diagnoses, did not meet protocol requirements, had inconsistent demographic information, or had less than 3 clinical assessments., Exposures: Exposures included (1) clinical and neuroimaging features at the first demyelinating attack and (2) presenting PIRA, ie, confirmed disability accumulation (CDA) in a free-relapse period at any time after symptom onset, within (vs after) the first 5 years of the disease (ie, early/late PIRA), and in the presence (vs absence) of new T2 lesions in the previous 2 years (ie, active/nonactive PIRA)., Main Outcomes and Measures: Expanded Disability Status Scale (EDSS) yearly increase rates since the first attack and adjusted hazard ratios (HRs) for predictors of time to PIRA and time to EDSS 6.0., Results: Of the 1128 patients (mean [SD] age, 32.1 [8.3] years; 781 female individuals [69.2%]) included in the study, 277 (25%) developed 1 or more PIRA events at a median (IQR) follow-up time of 7.2 (4.6-12.4) years (for first PIRA). Of all patients with PIRA, 86 of 277 (31%) developed early PIRA, and 73 of 144 (51%) developed active PIRA. Patients with PIRA were slightly older, had more brain lesions, and were more likely to have oligoclonal bands than those without PIRA. Older age at the first attack was the only predictor of PIRA (HR, 1.43; 95% CI, 1.23-1.65; P < .001 for each older decade). Patients with PIRA had steeper EDSS yearly increase rates (0.18; 95% CI, 0.16-0.20 vs 0.04; 95% CI, 0.02-0.05; P < .001) and an 8-fold greater risk of reaching EDSS 6.0 (HR, 7.93; 95% CI, 2.25-27.96; P = .001) than those without PIRA. Early PIRA had steeper EDSS yearly increase rates than late PIRA (0.31; 95% CI, 0.26-0.35 vs 0.13; 95% CI, 0.10-0.16; P < .001) and a 26-fold greater risk of reaching EDSS 6.0 from the first attack (HR, 26.21; 95% CI, 2.26-303.95; P = .009)., Conclusions and Relevance: Results of this cohort study suggest that for patients with multiple sclerosis, presenting with PIRA after a first demyelinating event was not uncommon and suggests an unfavorable long-term prognosis, especially if it occurs early in the disease course.

Intrathecal production of kappa free light chains occurs in multiple sclerosis and can be measured using the kappa free light chain index. Kappa free light chain index values can be determined more easily than oligoclonal bands detection and seem more sensitive than the immunoglobulin (Ig)G index to diagnose multiple sclerosis. We assessed the value of oligoclonal bands, kappa free light chain index cut-offs 5.9, 6.6 and 10.61, and IgG index to diagnose multiple sclerosis with prospectively acquired data from a clinically isolated syndrome inception cohort. We selected patients with sufficient data to determine oligoclonal bands positivity, MRI dissemination in space and time, IgG index and sufficient quantities of paired CSF and blood samples to determine kappa free light chain indexes (n = 214). We used Kendall's Tau coefficient to estimate concordance, calculated the number of additional diagnoses when adding each positive index to dissemination in space and positive oligoclonal bands, performed survival analyses for oligoclonal bands and each index with the outcomes second attack and 2017 MRI dissemination in space and time and estimated the diagnostic properties of oligoclonal bands and the different indexes for the previously mentioned outcomes at 5 years. Oligoclonal bands were positive in 138 patients (64.5%), kappa free light chain-5.9 in 136 (63.6%), kappa free light chain-6.6 in 135 (63.1%), kappa free light chain-10.61 in 126 (58.9%) and IgG index in 101 (47.2%). The highest concordance was between oligoclonal bands and kappa free light chain-6.6 (τ = 0.727) followed by oligoclonal bands and kappa free light chain-5.9 (τ = 0.716). Combining dissemination in space plus oligoclonal bands or kappa free light chain-5.9 increased the number of diagnosed patients by 11 (5.1%), with kappa free light chain-6.6 by 10 (4.7%), with kappa free light chain-10.61 by 9 (4.2%) and with IgG index by 3 (1.4%). Patients with positive oligoclonal bands or indexes reached second attack and MRI dissemination in space and time faster than patients with negative results (P < 0.0001 except IgG index in second attack: P = 0.016). In multivariable Cox models [adjusted hazard ratio (95% confidence interval)], the risk for second attack was very similar between kappa free light chain-5.9 [2.0 (0.9-4.3), P = 0.068] and kappa free light chain-6.6 [2.1 (1.1-4.2), P = 0.035]. The highest risk for MRI dissemination in space and time was demonstrated with kappa free light chain-5.9 [4.9 (2.5-9.6), P < 0.0001], followed by kappa free light chain-6.6 [3.4 (1.9-6.3), P < 0.0001]. Kappa free light chains-5.9 and -6.6 had a slightly higher diagnostic accuracy than oligoclonal bands for second attack (70.5, 71.1 and 67.8) and MRI dissemination in space and time (85.7, 85.1 and 81.0). Kappa free light chain indexes 5.9 and 6.6 performed slightly better than oligoclonal bands to assess multiple sclerosis risk and in terms of diagnostic accuracy. Given the concordance between oligoclonal bands and these indexes, we suggest using dissemination in space plus positive oligoclonal bands or positive kappa free light chain index as a modified criterion to diagnose multiple sclerosis., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: The recommendation for pertussis vaccination in pregnancy was established in Catalonia in February 2014. The objective of this study was to compare the hospitalisation rate for pertussis in children under one year of age before and after the implementation of the vaccination programme., Methods: Observational and retrospective study of patients under one year of age admitted to hospital with a diagnosis of pertussis. The hospitalisation rate of patients under one year of age of the period prior to the vaccination programme (2008-2013) was compared with the period with vaccination programme (2014-2019) in the total of children under one year of age and in 2 subgroups: children under 3 months and between 3-11 months., Results: Hospitalization rate was significantly lower in the period with vaccination programme in children under one year of age and specifically in children under 3 months (2.43 vs. 4.72 per 1000 person-years and 6.47 vs. 13.11 per 1000 person-years, respectively). The rate ratios were: 0.51 (95% CI 0.36-0.73) for children under one year of age; 0.49 (95% CI 0.32-0.75) for those younger than 3 months and 0.56 (95% CI 0.30-1.03) for those with 3-11 months. No statistically significant differences were observed in the clinical severity between both periods., Conclusion: The introduction of the pertussis vaccination programme in pregnancy was associated with a global lower hospitalisation rate for pertussis in children under one year of age and specifically in those under 3 months of age., (Copyright © 2022. Published by Elsevier España, S.L.U.)

Over the recent years, the treatment of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) has evolved very rapidly and a large number of disease-modifying treatments (DMTs) are now available. However, most DMTs are associated with adverse events, the most frequent of which being infections. Consideration of all DMT-associated risks facilitates development of risk mitigation strategies. An international focused workshop with expert-led discussions was sponsored by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and was held in April 2021 to review our current knowledge about the risk of infections associated with the use of DMTs for people with MS and NMOSD and corresponding risk mitigation strategies. The workshop addressed DMT-associated infections in specific populations, such as children and pregnant women with MS, or people with MS who have other comorbidities or live in regions with an exceptionally high infection burden. Finally, we reviewed the topic of DMT-associated infectious risks in the context of the current SARS-CoV-2 pandemic. Herein, we summarize available evidence and identify gaps in knowledge which justify further research.

Background: The effect of disease-modifying therapies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine response is unclear., Objectives: We aim to determine the immunological responses to SARS-CoV-2 in multiple sclerosis (MS) and anti-CD20-treated patients with other autoimmune diseases (AID)., Methods: Humoral and cellular responses we determined before and 30-90 days after vaccination in patients with MS and anti-CD20-treated patients with other AID in two Catalan centers., Results: 457 patients were enrolled. Findings showed that humoral response decreased under anti-CD20s or sphingosine 1-phosphate receptor modulators (S1PRM) and with longer treatment duration and increased after 4.5 months from the last anti-CD20 infusion. Cellular response decreased in S1PRM-treated. Patients on anti-CD20 can present cellular responses even in the absence of antibodies., Conclusion: Anti-CD20s and S1PRM modify the immunological responses to SARS-CoV-2 vaccines.