Safety and efficacy of rituximab as first- and second line treatment in multiple sclerosis – A cohort study

Background Rituximab is increasingly used as off-label therapy in multiple sclerosis (MS). More data are needed on safety and efficacy of rituximab, particularly in cohorts of de novo patients and patients in early therapy escalation. Objective To investigate the safety and efficacy of off-label treatment with rituximab in an MS-cohort of predominantly de novo patients or as therapy escalation. Methods We retrieved safety and efficacy data from the Norwegian MS-registry and biobank for all MS-patients treated with rituximab at Haukeland University Hospital, Bergen, Norway, during a four year period. Results In the 365 MS-patients (320 relapsing-remitting MS (RRMS), 23 secondary progressive MS (SPMS), and 22 primary progressive MS (PPMS)), the overall annualized relapse rate (ARR) was 0.03 and annualized drug discontinuation rate (ADDR) was 0.05. NEDA-3 was achived in 79% of patients with available data (n=351). Sixty-one patients experienced infusion-related adverse events of which two were serious (CTCAE grade 3–4). Eighteen patients experienced serious non-infusion related adverse events, of which 16 were infections. Infections (n = 34; 9.3%, CTCAE grade 2-5), hypogammaglobulinemia (n = 19, 5.2%) and neutropenia (n = 16; 4.4%) were the most common non-infusion-related adverse events. Conclusion Rituximab was a safe and highly efficient disease modifying therapy in this cohort of MS-patients; however, infections and neutropenia need to be monitored.publishedVersio

Humoral immunity to SARS-CoV-2 mRNA vaccination in multiple sclerosis: the relevance of time since last rituximab infusion and first experience from sporadic revaccinations

Introduction The effect of disease-modifying therapies (DMT) on vaccine responses is largely unknown. Understanding the development of protective immunity is of paramount importance to fight the COVID-19 pandemic. Objective To characterise humoral immunity after mRNA-COVID-19 vaccination of people with multiple sclerosis (pwMS). Methods All pwMS in Norway fully vaccinated against SARS-CoV-2 were invited to a national screening study. Humoral immunity was assessed by measuring anti-SARS-CoV-2 SPIKE RBD IgG response 3–12 weeks after full vaccination, and compared with healthy subjects. Results 528 pwMS and 627 healthy subjects were included. Reduced humoral immunity (anti-SARS-CoV-2 IgG <70 arbitrary units) was present in 82% and 80% of all pwMS treated with fingolimod and rituximab, respectively, while patients treated with other DMT showed similar rates as healthy subjects and untreated pwMS. We found a significant correlation between time since the last rituximab dose and the development of humoral immunity. Revaccination in two seronegative patients induced a weak antibody response. Conclusions Patients treated with fingolimod or rituximab should be informed about the risk of reduced humoral immunity and vaccinations should be timed carefully in rituximab patients. Our results identify the need for studies regarding the durability of vaccine responses, the role of cellular immunity and revaccinations. This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.publishedVersio

Terapeutisk hypotermi etter hjertestans utenfor sykehus: : Hvor tidlig, hvor dypt og hvor lenge?

Abstract Therapeutic hypothermia (TH) is currently recommended by international guidelines in comatose patients primary resuscitated after out-of-hospital cardiac arrest (OHCA). Todays’ recommendation is that TH is initiated as soon as possible, with a temperature of 32°-34°C, and a 12-24 hours duration. In this form it has been shown to significantly increase outcome in OHCA patients, with randomized controlled trials indicating a number needed to treat of 6. However, evidence regarding specific targets in the treatment recommendations are lacking or not convincing. Thus, the aim of this literature review is to evaluate available knowledge about some specific parameters in treatment with TH after OHCA in adults: Optimal initiation time, target temperature and duration. Twenty papers were included in a literature review. It was not possible to point out a definitive time window in which TH is effective. Several animal studies show a beneficial effect of early cooling and a general deleterious effect of delay. Clinical studies indicate that both intra-arrest and post-arrest induced TH could be feasible in a clinical setting. However, clinical studies have so far failed to show beneficial effects of early cooling. Feasible cooling methods should be used in randomized clinical trials to determine the clinical time window in which therapeutic hypothermia is effective. Too deep hypothermia is probably detrimental, since animal studies show serious cardiovascular adverse effects at temperatures between 15°C and 30°C. If even milder hypothermia (36°C) is as effective as the current recommended temperature of around 33°C, is under investigation in an ongoing randomized multicenter study. There are few animal studies comparing different duration of TH after OHCA, and the study results are diverging. A recent study, however, do indicate that prolonged duration might be beneficial, and clinical studies are needed to confirm todays’ practice of 12- 24 hours cooling. Importantly, studies on TH in OHCA patients should apply a sufficient follow-up time in order to ensure correct evaluation of outcome

Ventilatorassosiert pneumoni : Bruk av klorheksidin ved munnvask for å redusere forekomsten av pneumoni hos pasienter under respiratorbehandling

Ventilator-assosiert-pneumoni (VAP) er en hyppig forekommende og alvorlig tilstand hos intensivpasienter. Denne oppgaven omhandler et tenkt kunnskapsforbedringsprosjekt og beskriver munnstell med klorheksidin som et profylaktisk tiltak mot VAP. Vi valgte vårt tema med utgangspunkt i en kommentar publisert i Tidsskrift for Den norske legeforening i mars 2012 som anbefaler oral applikasjon med klorheksidin 2 % konsentrasjon for å forebygge pneumoni hos pasienter under respiratorbehandling (1). Vi utførte et systematisk søk i McMaster Plus og valgte å bruke UpToDate, Best Practice og en nylig publisert oppsummert oversiktsartikkel i Lancet Infection Disease som vårt kildegrunnlag. UpToDate anbefaler bruk av 0,12 % konsentrasjon, mens både Best Practice og Lancet-artikkelen angir at bruk av 2 % klorheksidin gir best effekt (2-4). Vi tok utgangspunkt i praksis ved intensivavdelingen ved Bærum Sykehus, hvor intuberte pasienter får munnstell etter gjeldende rutine to ganger daglig. Munnstellet inkluderer som hovedregel ikke bruk av klorheksidin. Vårt forslag til tiltak er å implementere pensling med 2 % klorheksidinløsning som en del av eksisterende munnstellprosedyre to ganger daglig. Vi valgte to indikatorer for å evaluere kvaliteten på dette prosjektet. Resultatindikatoren vår er ”antall respiratorbehandlede pasienter med pneumoni”, og prosessindikatoren vår er ”sjekkliste for om tiltaket utføres”. Forslag til gjennomføring av tiltaket baserer seg på PUKK-sirkelen. Prosessen foreslås organisert rundt en ansvarsgruppe med etablering av systemer for fortløpende kommunikasjon og innrapportering av problemer. Vi har gjennomgått kunnskapsgrunnlaget og foreslått et forbedringstiltak når det gjelder munnhygiene hos intuberte pasienter, og vi mener dette er gjennomførbart. Det vil være opp til den enkelte avdelingen å vurdere om de ønsker å gjennomføre tiltaket. I denne vurderingen må de bestemme seg for om de syns evidensen og fordelene med tiltaket er tilstrekkelige til at prosjektet bør igangsettes

Safety and efficacy of rituximab as first- and second line treatment in multiple sclerosis – A cohort study

Background Rituximab is increasingly used as off-label therapy in multiple sclerosis (MS). More data are needed on safety and efficacy of rituximab, particularly in cohorts of de novo patients and patients in early therapy escalation. Objective To investigate the safety and efficacy of off-label treatment with rituximab in an MS-cohort of predominantly de novo patients or as therapy escalation. Methods We retrieved safety and efficacy data from the Norwegian MS-registry and biobank for all MS-patients treated with rituximab at Haukeland University Hospital, Bergen, Norway, during a four year period. Results In the 365 MS-patients (320 relapsing-remitting MS (RRMS), 23 secondary progressive MS (SPMS), and 22 primary progressive MS (PPMS)), the overall annualized relapse rate (ARR) was 0.03 and annualized drug discontinuation rate (ADDR) was 0.05. NEDA-3 was achived in 79% of patients with available data (n=351). Sixty-one patients experienced infusion-related adverse events of which two were serious (CTCAE grade 3–4). Eighteen patients experienced serious non-infusion related adverse events, of which 16 were infections. Infections (n = 34; 9.3%, CTCAE grade 2-5), hypogammaglobulinemia (n = 19, 5.2%) and neutropenia (n = 16; 4.4%) were the most common non-infusion-related adverse events. Conclusion Rituximab was a safe and highly efficient disease modifying therapy in this cohort of MS-patients; however, infections and neutropenia need to be monitored

Humoral immunity to SARS-CoV-2 mRNA vaccination in multiple sclerosis: The relevance of time since last rituximab infusion and first experience from sporadic revaccinations

Introduction The effect of disease-modifying therapies (DMT) on vaccine responses is largely unknown. Understanding the development of protective immunity is of paramount importance to fight the COVID-19 pandemic. Objective To characterise humoral immunity after mRNA-COVID-19 vaccination of people with multiple sclerosis (pwMS). Methods All pwMS in Norway fully vaccinated against SARS-CoV-2 were invited to a national screening study. Humoral immunity was assessed by measuring antiSARS-CoV-2 SPIKE RBD IgG response 3–12 weeks after full vaccination, and compared with healthy subjects. Results 528 pwMS and 627 healthy subjects were included. Reduced humoral immunity (anti-SARS-CoV-2 Ig

Humoral immunity to SARS-CoV-2 mRNA vaccination in multiple sclerosis: the relevance of time since last rituximab infusion and first experience from sporadic revaccinations

Introduction: The effect of disease-modifying therapies (DMT) on vaccine responses is largely unknown. Understanding the development of protective immunity is of paramount importance to fight the COVID-19 pandemic. Objective: To characterise humoral immunity after mRNA-COVID-19 vaccination of people with multiple sclerosis (pwMS). Methods: All pwMS in Norway fully vaccinated against SARS-CoV-2 were invited to a national screening study. Humoral immunity was assessed by measuring anti-SARS-CoV-2 SPIKE RBD IgG response 3–12 weeks after full vaccination, and compared with healthy subjects. Results: 528 pwMS and 627 healthy subjects were included. Reduced humoral immunity (anti-SARS-CoV-2 IgG <70 arbitrary units) was present in 82% and 80% of all pwMS treated with fingolimod and rituximab, respectively, while patients treated with other DMT showed similar rates as healthy subjects and untreated pwMS. We found a significant correlation between time since the last rituximab dose and the development of humoral immunity. Revaccination in two seronegative patients induced a weak antibody response. Conclusions: Patients treated with fingolimod or rituximab should be informed about the risk of reduced humoral immunity and vaccinations should be timed carefully in rituximab patients. Our results identify the need for studies regarding the durability of vaccine responses, the role of cellular immunity and revaccinations

Humoral immunity to SARS-CoV-2 mRNA vaccination in multiple sclerosis: the relevance of time since last rituximab infusion and first experience from sporadic revaccinations

Introduction The effect of disease-modifying therapies (DMT) on vaccine responses is largely unknown. Understanding the development of protective immunity is of paramount importance to fight the COVID-19 pandemic. Objective To characterise humoral immunity after mRNA-COVID-19 vaccination of people with multiple sclerosis (pwMS). Methods All pwMS in Norway fully vaccinated against SARS-CoV-2 were invited to a national screening study. Humoral immunity was assessed by measuring anti-SARS-CoV-2 SPIKE RBD IgG response 3–12 weeks after full vaccination, and compared with healthy subjects. Results 528 pwMS and 627 healthy subjects were included. Reduced humoral immunity (anti-SARS-CoV-2 IgG <70 arbitrary units) was present in 82% and 80% of all pwMS treated with fingolimod and rituximab, respectively, while patients treated with other DMT showed similar rates as healthy subjects and untreated pwMS. We found a significant correlation between time since the last rituximab dose and the development of humoral immunity. Revaccination in two seronegative patients induced a weak antibody response. Conclusions Patients treated with fingolimod or rituximab should be informed about the risk of reduced humoral immunity and vaccinations should be timed carefully in rituximab patients. Our results identify the need for studies regarding the durability of vaccine responses, the role of cellular immunity and revaccinations. This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained