scholarly journals Long-Term Efficacy Outcomes of Natalizumab vs. Fingolimod in Patients With Highly Active Relapsing-Remitting Multiple Sclerosis: Real-World Data From a Multiple Sclerosis Reference Center

2021 ◽  
Vol 12 ◽  
Author(s):  
Marina Boziki ◽  
Christos Bakirtzis ◽  
Virginia Giantzi ◽  
Styliani-Aggeliki Sintila ◽  
Stylianos Kallivoulos ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Real World ◽  
Rank Test ◽  
Real World Data ◽  
Log Rank Test ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Background: Natalizumab (NTZ) and fingolimod (FTY) are second-line disease modifying treatments (DMTs) approved for Relapsing – Remitting Multiple Sclerosis (RRMS). Few studies are available on a direct comparison between NTZ and FTY, based on post-marketing experience, with conflicting results and reporting relatively short follow-up period.Aim: We hereby report real-world experience of a MS Center with respect to NTZ vs. FTY comparison in terms of efficacy and safety, referencing long-term follow-up.Methods: We used retrospective data for all patients that received 2nd-line treatment NTZ (since May 2007) or FTY (since September 2011). Primary endpoints were, among others, annual EDSS score (mean change from baseline), time to disability worsening or improvement, Annualized Relapse Rate (ARR) after 12 and 24 months and upon total treatment duration, time to first relapse and time to radiological progression.Results: A total of 138 unmatched patients, 84 treated with NTZ and 54 treated with FTY were included. Following Propensity Score (PS) matching, 31 patients in each group were retained. Mean follow-up period for NTZ- and FTY-treated patients was 4.43 ± 0.29 and 3.59 ± 0.32 years (p = 0.057), respectively. In the matched analysis, time to disability improvement and time to disability worsening was comparable between groups. A higher proportion of patients remained free of relapse under NTZ, compared to FTY (Log Rank test p = 0.021, HR: 0.25, 95% CI: 0.08–0.8), as well as free of MRI activity (Log Rank test p = 0.006, HR: 0.26, 95% CI: 0.08–0.6). Treatment discontinuation due to MRI activity was significantly higher for FTY-treated patients compared to NTZ (Log Rank test p = 0.019, HR: 0.12, 95% CI: 0.05–0.76).Conclusion: Our results indicate toward NTZ superiority with respect to relapse and MRI activity outcomes. The fact that NTZ-treated patients may achieve long-standing clinical and radiological remission points toward the need for long follow-up data.

scholarly journals Alemtuzumab in the long-term treatment of relapsing-remitting multiple sclerosis: an update on the clinical trial evidence and data from the real world

2017 ◽  
Vol 10 (10) ◽  
pp. 343-359 ◽  
Author(s):  
Tjalf Ziemssen ◽  
Katja Thomas
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Events ◽  
Mechanism Of Action ◽  
Real World ◽  
Continuous Treatment ◽  
The Real ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Alemtuzumab is a humanized monoclonal antibody approved for the treatment of relapsing-remitting multiple sclerosis (RRMS), given as two annual courses on five consecutive days at baseline and on three consecutive days 12 months later. Here we provide an update on the long-term efficacy and safety of alemtuzumab in RRMS, including real-world experience, and advances in our understanding of its mechanism of action. Recent data from the phase II/III extension study have demonstrated that alemtuzumab reduces relapse rates, disability worsening, and the rate of brain volume loss over the long term, with many patients achieving no evidence of disease activity. In high proportions of patients, preexisting disability remained stable or improved. Alemtuzumab is associated with a consistent safety profile over the long term, with no new safety signals emerging and the overall annual incidence of reported adverse events decreasing after the first year on treatment. Acyclovir prophylaxis reduces herpetic infections, and monitoring has been shown to mitigate the risk of autoimmune adverse events, allowing early detection and overall effective management. Data from clinical practice and ongoing observational studies are providing additional information on the real-world use of alemtuzumab. Recent evidence on the mechanism of action of alemtuzumab indicates that in addition to its previously known effects of inducing depletion and repopulation of T and B lymphocytes, it also results in a relative increase of cells with memory and regulatory phenotypes and a decrease in cells with a proinflammatory signature, and may further promote an immunoregulatory environment through an impact on other innate immune cells (e.g. dendritic cells) that play a role in MS. These effects may allow preservation of innate immunity and immunosurveillance. Together, these lines of evidence help explain the durable clinical efficacy of alemtuzumab, in the absence of continuous treatment, in patients with RRMS.

Long-term disability outcomes in relapsing-remitting multiple sclerosis: a 10-year follow-up study

2019 ◽  
Vol 40 (8) ◽  
pp. 1627-1636 ◽  
Author(s):  
Jelena Drulovic ◽  
Jovana Ivanovic ◽  
Sarlota Mesaros ◽  
Vanja Martinovic ◽  
Darija Kisic-Tepavcevic ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Follow Up Study ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

LONG-TERM SAFETY OF ALEMTUZUMAB IN RELAPSING-REMITTING MULTIPLE SCLEROSIS: PREGNANCY AND INFECTION DATA FROM A COHORT OF PATIENTS ON OPEN LABEL STUDIES IN CAMBRIDGE

2015 ◽  
Vol 86 (11) ◽  
pp. e4.15-e4
Author(s):  
Claire McCarthy ◽  
Orla Tuohy ◽  
Laura Azzopardi ◽  
Onajite Kousin-Ezewu ◽  
Joanne Jones ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Varicella Zoster Virus ◽  
Open Label ◽  
Varicella Zoster ◽  
Serious Infections ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

BackgroundAlemtuzumab is recently licensed for use in active relapsing-remitting multiple sclerosis (RRMS) in Europe and the USA. This observational cohort study investigated the long term safety of alemtuzumab in RRMS.MethodsClinical data was collected from a cohort of 87 patients who participated in open label studies of alemtuzumab in Cambridge, UK from 1999 to 2012. Pregnancy outcomes and the occurrence of moderate to severe infections were recorded.ResultsOver a median 7-year follow-up (range 33–144 months), no serious infections occurred that required hospitalisation. There were 11 cases of varicella zoster virus reactivation and one case of primary varicella zoster virus infection. In this cohort 15 babies were born to 12 women treated with alemtuzumab. The median interval from their most recent alemtuzumab treatment to birth was 26 months (range 13–86 months). All of the babies were healthy and delivered without complications. One woman had experienced a miscarriage at 8 weeks gestation but went on to have two successful pregnancies.ConclusionsDuring prolonged follow-up of this cohort of patients treated with alemtuzumab no serious infections occurred. No increased risk of miscarriage or foetal abnormality was seen in the small number of pregnancies studied.

scholarly journals Impact of drug diversity on treatment effectiveness in relapsing-remitting multiple sclerosis (RRMS) in Germany between 2010 and 2018: real-world data from the German NeuroTransData multiple sclerosis registry

BMJ Open ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. e042480
Author(s):  
Stefan Braune ◽  
Fabian Rossnagel ◽  
Heidi Dikow ◽  
Arnfin Bergmann
Keyword(s):  
Multiple Sclerosis ◽  
Real World ◽  
Treatment Effectiveness ◽  
Real World Data ◽  
World Data ◽  
Conversion Rates ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis ◽  
The Impact

ObjectiveTo evaluate the impact of drug diversity on treatment effectiveness in relapsing-remitting multiple sclerosis (RRMS) in Germany.DesignThis study employs real-world data captured in-time during clinical visits in 67 German neurology outpatient offices of the NeuroTransData (NTD) multiple sclerosis (MS) registry between 1 January 2010 and 30 June 2019, including 237 976 visits of 17 553 patients with RRMS. Adherence and clinical effectiveness parameters were analysed by descriptive statistics, time-to-event analysis overall and by disease-modifying therapies (DMTs) stratified by administration modes (injectable, oral and infusion). Three time periods were compared: 2010–2012, 2013–2015 and 2016–2018.ResultsBetween 2010 and 2018, an increasing proportion of patients with RRMS were treated with DMTs and treatment was initiated sooner after diagnosis of MS. Introduction of oral DMT temporarily induced higher readiness to switch. Comparing the three index periods, there was a continuous decrease of annualised relapse rates, less frequent Expanded Disability Status Scale (EDSS) progression and increasing periods without relapse, EDSS worsening and with stability of no-evidence-of-disease-activity 2 and 3 criteria, lower conversion rates to secondary progressive MS on oral and on injectable DMTs.ConclusionSparked by the availability of new mainly oral DMTs, RRMS treatment effectiveness improved clinically meaningful between 2010 and 2018. As similar effects were seen for injectable and oral DMTs more than for infusions, a better personalised treatment allocation in many patients is likely. These results indicate that there is an overall beneficial effect for the whole patient with MS population as a result of the greater selection of available DMTs, a benefit beyond the head-to-head comparative efficacy, resulting from an increased probability and readiness to individualise MS therapy.

scholarly journals Long-term safety and efficacy of dimethyl fumarate for up to 13 years in patients with relapsing-remitting multiple sclerosis: Final ENDORSE study results

2021 ◽  
pp. 135245852110379
Author(s):  
Ralf Gold ◽  
Douglas L Arnold ◽  
Amit Bar-Or ◽  
Robert J Fox ◽  
Ludwig Kappos ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Events ◽  
Dimethyl Fumarate ◽  
Phase Iii ◽  
Study Results ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Background: Dimethyl fumarate (DMF) demonstrated favorable benefit–risk in relapsing-remitting multiple sclerosis (RRMS) patients in phase-III DEFINE and CONFIRM trials, and ENDORSE extension. Objective: The main aim of this study is assessing DMF safety/efficacy up to 13 years in ENDORSE. Methods: Randomized patients received DMF 240 mg twice daily or placebo (PBO; Years 0–2), then DMF (Years 3–10; continuous DMF/DMF or PBO/DMF); maximum follow-up (combined studies), 13 years. Results: By January 2020, 1736 patients enrolled/dosed in ENDORSE (median follow-up 8.76 years (ENDORSE range: 0.04–10.98) in DEFINE/CONFIRM and ENDORSE); 52% treated in ENDORSE for ⩾6 years. Overall, 551 (32%) patients experienced serious adverse events (mostly multiple sclerosis (MS) relapse or fall; one progressive multifocal leukoencephalopathy); 243 (14%) discontinued treatment due to adverse events (4% gastrointestinal (GI) disorders). Rare opportunistic infections, malignancies, and serious herpes zoster occurred, irrespective of lymphocyte count. For DMF/DMF ( n = 501), overall annualized relapse rate (ARR) remained low (0.143 (95% confidence interval (CI), 0.120–0.169)), while for PBO/DMF ( n = 249), ARR decreased after initiating DMF and remained low throughout (ARR 0–2 years, 0.330 (95% CI, 0.266–0.408); overall ARR (ENDORSE, 0.151 (95% CI, 0.118–0.194)). Over 10 years, 72% DMF/DMF and 73% PBO/DMF had no 24-week confirmed disability worsening. Conclusion: Sustained DMF safety/efficacy was observed in patients followed up to 13 years, supporting DMF’s positive benefit/risk profile for long-term RRMS treatment.

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