Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 9 de 9
Filter
Add filters

Language
Document Type
Year range
1.
Multiple Sclerosis Journal ; 28(3 Supplement):359-360, 2022.
Article in English | EMBASE | ID: covidwho-2138904

ABSTRACT

Introduction: Ozanimod, an oral sphingosine 1-phosphate receptor 1 and 5 modulator, is approved in multiple countries for the treatment of adults with either relapsing forms of multiple sclerosis (RMS) or moderately to severely active ulcerative colitis. Objective(s): To report the safety and efficacy of extended exposure to ozanimod from an ongoing open-label extension (OLE) trial. Method(s): Patients with RMS who completed a phase 1, 2, or 3 ozanimod trial were eligible to enrol in DAYBREAK (NCT02576717), where they received ozanimod 0.92 mg/d. The primary objective was to evaluate safety in the overall population;treatment-emergent adverse events (TEAE) were monitored. Efficacy was evaluated with annualised relapse rate (ARR), calculated via negative binomial regression and pooled for all parent-trial treatment groups. Number of new/ enlarging T2 and gadolinium-enhancing (GdE) magnetic resonance imaging (MRI) brain lesions were reported for patients who entered the OLE from an active-controlled phase 3 trial. Result(s): In total, 2639 patients completed the parent trials;this interim analysis (datacut 1 February 2022) included 2494 patients with mean (range) ozanimod exposure of 56.4 (0.03- 74.7) months (11732.2 patient-years) in the OLE. In the OLE, 2199 patients (88.2%) had any TEAE, 352 (14.1%) had a serious TEAE (SAE), and 89 (3.6%) discontinued due to a TEAE. Similar rates of TEAEs and SAEs occurred when assessed by parent trial treatment group. The most common TEAEs (based on preferred terms) were nasopharyngitis (20.6%), headache (16.9%), upper respiratory tract infection (11.9%), COVID- 19 infection (11.5%), and lymphopenia (10.5%), which were generally similar to parent trial observations (excluding COVID-19 infection). Adjusted ARR in the OLE was 0.099 (95% CI, 0.083-0.119). After 60 months of treatment, 68% of patients were relapse free in the OLE. Three- and 6-month confirmed disability progression was observed in 15.9% and 14.0% of patients in the OLE, respectively. Mean number of new/enlarging T2 lesions per scan at 60 months was similar, regardless of parent trial treatment group (range, 0.77-0.98), as was mean number of GdE lesions at month 60 (range, 0.057-0.065). Conclusion(s): The safety and tolerability profile of ozanimod in DAYBREAK was consistent with prior reports. Ozanimod treatment demonstrated sustained efficacy on clinical and MRI measures of disease activity and on disability progression.

2.
Multiple Sclerosis Journal ; 28(3 Supplement):354-355, 2022.
Article in English | EMBASE | ID: covidwho-2138866

ABSTRACT

Introduction: The long-term benefit-risk profile of ocrelizumab (OCR) in patients (pts) with multiple sclerosis (MS) can be evaluated by regular safety reporting of clinical trial (CT) and post-marketing (PM) data. Safety/efficacy of OCR have been characterised in Phase II (NCT00676715) and Phase III (NCT01247324;NCT01412333;NCT01194570) trials and related open-label extension (OLE) periods, in relapsing-remitting MS, relapsing MS (RMS) and primary progressive MS (PPMS). It is important to understand the long-term safety profile of OCR and consider the impact of COVID-19. Aim(s): To report the continuity in safety by reporting longer-term safety evaluations from OCR CT and OLE periods over a 9-year follow-up period (up to November 2021). Method(s): Safety outcomes, with and without COVID-19, are reported for the OCR all-exposure population from 11 ongoing CTs in MS. Rates per 100 patient years (PY) are presented. Result(s): Over more than 9 years of follow-up, 5,848 pts with MS received OCR treatment in 11 CTs (25,153 PY of exposure;November 2021). Reported rates per 100 PY (95% CI) were: Adverse events (AEs), 232.71 (230.83-234.60), [excluding COVID-19 (EX COV) 230.12 (228.25-232.01)];infections, 69.89 (68.86-70.93), [EX COV 67.37 (66.36-68.39)];serious AEs, 7.61 (7.27-7.96), [EX COV 6.90 (6.58-7.23)];serious infections (SI), 2.74 (2.54-2.96), [EX COV 2.04 (1.87-2.22)];malignancies, 0.41 (0.34-0.50);SI leading to withdrawal, 0.12 (0.08-0.18), [EX COV 0.08 (0.05-0.13)];and AEs leading to discontinuation, 0.97 (0.85-1.10), [EX COV 0.93 (0.81-1.06)]. As of March 2022, over 250,000 pts with MS initiated OCR globally in the PM setting. Data remain generally consistent with those observed in CTs factoring in the impact of the COVID-19 pandemic. Conclusion(s): AE rates in the OCR all-exposure population remain generally consistent with the controlled treatment period in RMS/PPMS populations. Serious infection and malignancy rates remain within the range reported for pts with MS in realworld registries. COVID-19 did not lead to increased treatment withdrawal. Over a 9-year follow-up period, no new or unexpected safety signal was seen in pts treated with OCR in ongoing CTs. OCR continues to exhibit a stable and favourable safety profile. Regular reporting of longer-term safety data will continue.

3.
Multiple Sclerosis Journal ; 28(3 Supplement):345-346, 2022.
Article in English | EMBASE | ID: covidwho-2138856

ABSTRACT

Introduction: In patients with Multiple Sclerosis (pwMS), specific disease modifying treatments (DMTs) may compromise immune response following SARS-CoV-2 vaccination. Limited information is available, whether levels of anti-SARS-CoV-2 antibodies are linked to the risk of breakthrough infections in pwMS. Objective(s): To determine the rate of Omicron breakthrough infection and severity of COVID-19 in a cohort of MS patients treated with different DMTs and to estimate the impact of SARSCoV- 2-specific antibody level on breakthrough infection risk. Method(s): This study is nested within the Swiss MS Cohort, a nationwide multicenter study that has recruited 1585 pwMS. Patients who received two doses of SARS-CoV-2 vaccines before Omicron became the dominant variant in Switzerland on Dec-15, 2021 and had a follow-up thereafter were included. Data on SARS-CoV-2 infections, severity of COVID-19 according to the WHO scale and SARS-CoV-2 vaccines were collected by questionnaires. Anti-SARS-CoV-2-S antibody levels were measured after the second vaccine dose. Incidence of infections grouped by antibody level after second vaccination was visualized using Kaplan-Meier curves. Cox regression models were used to estimate the impact of antibody levels on the hazard of breakthrough infection during follow-up. Result(s): 242 pwMS (median age 49y [39,58], 162 (67%) female, 36 (15%) with progressive disease, median EDSS 2.5 [1.5,4.0]) were included. 22 (9%) had SARS-CoV-2 infection and 137 (57%) at least one additional vaccine dose prior to Omicron start. Since then, 57 breakthrough infections were reported. Severity of breakthrough disease on WHO scale ranged from 1-10: 7 were asymptomatic, 46 were symptomatic as outpatients, 3 were hospitalized and 1 died. Patients with antibody levels >150U/ml (n = 95, 39%) after second vaccination had a 64% reduced risk for Omicron breakthrough-infection compared to patients with antibody levels <0.7U/ml (n = 81, 33%) (HR 0.36, 95%CI=0.18- 0.71, p<0.01). This effect was maintained after adjustment for DMT at vaccination and time since second vaccination Conclusion(s): Humoral immune response after second SARSCoV- 2 vaccination is associated with Omicron breakthrough infection rate, a finding contrasting general populations, where antibody levels seem to have little impact on protecting from Omicron infection. Most breakthrough infections in our cohort were mild. Analyses on the effect of booster vaccinations on serology and infection rates will follow.

4.
Multiple Sclerosis Journal ; 28(3 Supplement):401-402, 2022.
Article in English | EMBASE | ID: covidwho-2138854

ABSTRACT

Introduction: COVID-19 emerged in late 2019. It is unclear whether selective sphingosine 1-phosphate (S1P) receptor modulators affect clinical outcomes of COVID-19 in patients with relapsing multiple sclerosis (RMS), including those who received SARS-CoV-2 vaccination. Objective(s): To characterise COVID-19 outcomes and vaccine breakthrough infections during ozanimod use, an S1P1 and S1P5 modulator, for treatment of RMS in an ongoing open-label extension (OLE) study. Method(s): DAYBREAK (NCT02576717), an OLE study of ozanimod 0.92 mg/d, began 16Oct2015. Patients who completed a phase 1-3 ozanimod RMS trial were eligible;>90% are from Eastern Europe. In this post hoc analysis, COVID-19 events from 1Nov2019 to 28Jan2022 in DAYBREAK were identified by MedDRA 24.1 COVID-19 SMQ (narrow scope). Each patient's most recent infection and all postvaccination infections were characterised. Result(s): Of 2181 patients in DAYBREAK during the analysis period, 319 (14.6%) developed COVID-19 (274 confirmed, 45 suspected). COVID-19 was nonserious in 291 (91.2%). During COVID-19, ozanimod was continued in 220 (69.0%) patients, interrupted in 94 (29.5%), and permanently discontinued in 3 (0.9%);action was unknown in 2 (0.6%) patients. At data cutoff, 285 (89.3%) had recovered (including 195 who had continued ozanimod), 6 (1.9%) recovered with sequelae, 5 (1.6%) were recovering, 16 (5.0%) had not recovered, and 5 (1.6%) died;a sixth COVID-19-related death due to lung abscess occurred after recovery with sequelae from COVID-19 infection. Of 1984 patients in DAYBREAK on 11Dec2020, when COVID-19 vaccines emerged, 596 (30.0%) received >=1 vaccine dose (415 [69.6%] mRNA;99 [16.6%] replication-defective viral vector;65 [10.9%] inactivated SARS-CoV-2;26 [4.4%] other);504 (25.4%) were fully vaccinated. COVID-19 occurred in 39/596 (6.5%) vaccinated patients and 213/1388 (15.3%) unvaccinated patients;3 postvaccination cases (including 1 case after 2 mRNA doses) were serious. Of 39 patients with postvaccination infections, 28 (71.8%) recovered (including 2/3 serious cases), 1 (2.6%) recovered with sequelae, 3 (7.7%) were recovering, and 7 (17.9%, including the third serious case) had not recovered at data cutoff. There were no COVID-19-related deaths among vaccinated patients. Conclusion(s): COVID-19 cases were largely nonserious, and the majority of infected patients recovered while continuing ozanimod. Few vaccinated patients developed COVID-19;most who did recovered without sequelae.

6.
Multiple Sclerosis Journal ; 27(2 SUPPL):607-608, 2021.
Article in English | EMBASE | ID: covidwho-1495999

ABSTRACT

Introduction: Ongoing consistent safety reporting is crucial to understand the long-term benefit-risk profile of ocrelizumab (OCR) in patients with multiple sclerosis (MS), in both clinical trials and globally, in the post-marketing (PM) setting. Safety/efficacy of OCR have been characterised in Phase II (NCT00676715) and Phase III (NCT01247324;NCT01412333;NCT01194570) trials and related open-label extension (OLE) periods, in patients with relapsing-remitting MS, relapsing MS (RMS) and primary progressive MS (PPMS). It is important to understand the longterm safety profile of OCR independent of any impact of COVID- 19 infections. Aims: To maintain continuity in the safety update by reporting longer-term safety evaluations from OCR clinical trials and OLE periods up to November 2020 and selected PM data, excluding COVID-19 cases;the latter will be communicated in a separate late-breaking abstract. Methods: Safety outcomes, excluding COVID-19, are reported for the OCR all-exposure population in Phase II/III trials and associated OLEs plus ongoing Phase IIIb trials in MS (VELOCE, CHORDS, CASTING, OBOE, ENSEMBLE, LIBERTO and CONSONANCE). To account for different exposure lengths, rates per 100 patient years (PY) are presented. The number of postmarketing OCR-treated patients is based on estimated number of vials sold and US claims data. Results: In clinical trials, 5,688 patients with MS received OCR (21,675 PY of exposure;Nov 2020). Reported rates per 100 PY (95% confidence interval) were: Adverse events (AEs), 238 (236- 240);infections, 71.8 (70.7-73.0);serious AEs, 7.05 (6.71-7.42);serious infections, 2.0 (1.82-2.20);malignancies, 0.42 (0.34- 0.52);and AEs leading to discontinuation, 0.96 (0.83-1.10). As of December 2020, over 200,000 patients with MS initiated OCR globally in the PM setting. Data remain generally consistent with those observed in clinical trials. Conclusions: AE rates in the OCR all-exposure population and PM settings, excluding COVID-19 infections, remain generally consistent with the controlled treatment period in RMS/PPMS populations. Serious infection and malignancy rates remain within the range reported for patients with MS in real-world registries. In patients with RMS and PPMS, OCR demonstrates a consistent and favourable safety profile;these longer-term data are in accordance with the safety outcomes initially observed during the controlled treatment periods. Regular reporting of longer-term safety data will continue.

7.
Multiple Sclerosis Journal ; 27(2 SUPPL):649-650, 2021.
Article in English | EMBASE | ID: covidwho-1495986

ABSTRACT

Background: COVID-19 disease course in MS has been described in various cohorts. Limited data is available on humoral immune responses following SARS-CoV-2 infection and vaccination. Objectives: To determine the rate of confirmed SARS-CoV-2 infection and severity of COVID-19 in a cohort of MS patients and to quantify SARS-CoV-2-specific antibody response. Methods: The study is nested within the Swiss MS Cohort, a nationwide multicenter study that has recruited 1504 persons with MS (pwMS) since 2012. PCR-confirmed SARS-CoV-2 infections, severity of COVID-19 according to the WHO clinical progression scale and immunizations with SARS-CoV-2 vaccines were captured by questionnaires used for interviews every 6 or 12 months. Anti-SARS-CoV-2 spike protein and nucleocapsid antibody levels will be determined by electrochemiluminescence immunoassay (ECLIA) (Elecsys, Anti-SARS-CoV-2, Roche Diagnostics) in sera of all participants. Results: Between February 2021 and April 2021, study questionnaires were completed for 253 pwMS (median age 47 years, 162 female). 211 pwMS (83%) had a relapsing, 25 (10%) a secondary progressive, 13 (5%) a primary progressive disease course and 4 (2%) a clinically isolated syndrome. Median disease duration was 12 years and median EDSS was 2.5. 218 (86%) pwMS were treated with DMTs: Ocrelizumab (27%), fingolimod (26%), dimethyl fumarate (15%), rituximab (10%), natalizumab (9%), other DMTs (13%). 15 (5.9%) of 253 pwMS had a positive SARSCoV- 2 PCR test since March 2020. In these pwMS, COVID-19 severity ranged from 1-10 on the WHO clinical progression scale: 1 pwMS was asymptomatic, 10 pwMS were symptomatic as outpatients (8 independently, 2 needed assistance), 3 pwMS were hospitalized (1 without oxygen therapy, 2 with oxygen by mask or nasal prongs) and 1 pwMS died. By April 2021, 24 and 38 pwMS received one and two doses of SARS-CoV-2 mRNA vaccines, respectively. Conclusions and outlook: Since start of the pandemic, rate of PCR-confirmed SARS-CoV-2 infection in our sample was slightly lower compared to incidence of laboratory-confirmed cases in Switzerland. The majority of pwMS had mild COVID-19. The study will continue until 2024 and by ECTRIMS 2021, we anticipate a doubling of completed questionnaires and to report preliminary results of serological measurements. This will allow us to present vaccine- and natural infection induced serological anti-SARS-CoV-2 responses in pwMS and assess differences related to various DMTs or COVID-19 severity.

8.
Multiple Sclerosis Journal ; 27(2 SUPPL):654-655, 2021.
Article in English | EMBASE | ID: covidwho-1495984

ABSTRACT

Introduction and Objectives: Long-term use of highly effective disease modifying treatments (DMT) can cause secondary immunodeficiency and consecutive, potentially life-threatening infectious complications. The main objective of this study is to identify factors for increased susceptibility to infections and to establish a prospective infection risk stratification tool for people with MS (pwMS). Methods: InRIMS is a monocentric, prospective, observational and comparative study, enrolling regularly followed pwMS from two cohort studies in Switzerland (SMSC and SUMMIT) since September 2019. Extending a validated infection questionnaire from the large population-based Airway Infection Susceptibility (AWIS) study, we developed an adapted survey with MS-specific items (MS-AWIS questionnaire). At baseline, all participants complete this MS-AWIS questionnaire, which allows calculating an infection risk (IR) score of weighted questionnaire items indicative for increased susceptibility to infections. In analogy to the AWIS study, IR scores ≤4, >4 to <17, and ≥17 correspond to a low, intermediate or high risk for airway infections, respectively. To assess the prognostic value of the IR score, frequency and severity of infections is prospectively recorded over two years using monthly, standardized infection diaries. In response to the SARS-COV2 pandemic, we also document cases of COVID-19 by an additive questionnaire. Results: By May 2021, 297 pwMS were enrolled in InRIMS (9 drop-outs). In a first interim-analysis we included 245 patients with baseline questionnaires (67% female, 87% under DMT, mean age of 48 years (SD ± 12,3 years), mean disease duration 13,3 years (SD ± 9,3 years), median BMI 21,5 (IQR 18,3:24,2)). The mean calculated IR score was 6,8 (SD± 5,5). 6,1% of the InRIMS study population had an IR score ≥17, which was indicative for an increased susceptibility to infections according to results of the population-based AWIS study. Discussion: The InRIMS study assesses risk factors for infections in the real world-setting of a well-defined MS cohort. In the first study phase, most participants enrolled before onset of the SARSCOV2 pandemic in Switzerland - enabling prospective infectious risk assessment. We envisage that the results of the InRIMS study will help to inform counselling of MS patients in clinical practice and support personalized treatment choices as well as preventive measures.

SELECTION OF CITATIONS
SEARCH DETAIL