scholarly journals Time course of lymphocyte repopulation after dimethyl fumarate-induced grade 3 lymphopenia: contribution of patient age

2019 ◽  
Vol 12 ◽  
pp. 175628641984345 ◽  
Author(s):  
Myriam Briner ◽  
Maud Bagnoud ◽  
Andrei Miclea ◽  
Christoph Friedli ◽  
Lara Diem ◽  
...  
Keyword(s):  
Time Course ◽  
Opportunistic Infections ◽  
Linear Regression Analysis ◽  
Dimethyl Fumarate ◽  
University Hospital ◽  
Multivariate Linear Regression Analysis ◽  
Retrospective Data Analysis ◽  
Relapsing Remitting ◽  
Grade 3 ◽  
Relapsing Remitting Multiple Sclerosis

Background: Dimethyl fumarate (DMF) is licensed for treatment of relapsing–remitting multiple sclerosis (RRMS). DMF can induce lymphopenia, which is assumed to increase the risk for opportunistic infections like progressive multifocal leukoencephalopathy. Our goal for this work was to estimate the frequency of grade 3 lymphopenia in DMF-treated patients with RRMS and to characterize patient-sided factors influencing the time course of lymphocyte repopulation after DMF withdrawal. Material and methods: A single-center retrospective data analysis was performed at University Hospital Bern, Switzerland. Patients with DMF treatment were analyzed for lymphocyte counts. Demographic factors were statistically analyzed in grade 3 lymphopenic patients. Results: We estimated a grade 3 lymphopenia frequency of 11/246 (4.5%), corroborating previous studies. In all patients, lymphocytes recovered to values ⩾800/µl within 0.5 years. Multivariate linear regression analysis unmasked older age as being associated with a longer duration of repopulation. Conclusion: Considering the aging population, our findings warrant further investigations of DMF-induced lymphopenia.

scholarly journals Phase I trial of dimethyl fumarate, temozolomide, and radiation therapy in glioblastoma

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Danielle Shafer ◽  
Mary Beth Tombes ◽  
Ellen Shrader ◽  
Alison Ryan ◽  
Dipankar Bandyopadhyay ◽  
...  
Keyword(s):  
Phase I ◽  
Progression Free Survival ◽  
Dimethyl Fumarate ◽  
Maximum Tolerated Dose ◽  
Newly Diagnosed ◽  
Relapsing Remitting ◽  
Common Grade ◽  
Grade 3 ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Dose Levels

Abstract Background Dimethyl fumarate (DMF), an oral agent approved for the treatment of relapsing–remitting multiple sclerosis (RRMS), has promising preclinical activity against glioblastoma (GBM). This phase I study sought to determine the recommended phase 2 dose (RP2D) of DMF and evaluate its safety and toxicity when combined with standard concurrent radiotherapy (RT) and temozolomide (TMZ) followed by maintenance TMZ in patients with newly diagnosed GBM. Methods Using a standard 3 + 3 dose-escalation design with 3 dose levels, patients received daily DMF with 60 Gy RT and concurrent TMZ 75 mg/m2 daily, followed by maintenance DMF (continuously) and TMZ 150–200 mg/m2 on days 1–5 of each 28-day cycle for up to 6 cycles. The maximum tolerated dose (MTD) was determined by evaluation of dose-limiting toxicity (DLT) during the first 6 weeks of therapy. Results Twelve patients were treated at the 3 dose levels, and no DLTs were observed. There were no unexpected toxicities. The most common grade 3/4 treatment related adverse events (AEs) were lymphopenia (58%), decreased CD4 count (17%), and thrombocytopenia (17%). Four patients completed all planned treatment; seven patients had progression on treatment. One patient chose to withdraw from the study during maintenance. The median progression-free survival (PFS) for all patients was 8.7 months with no difference in PFS between those with stable disease or a partial response; median overall survival was 13.8 months. Conclusions DMF may be safely combined with RT and TMZ in patients with newly diagnosed GBM. The RP2D for DMF is 240 mg three times daily.

scholarly journals Discontinuation and dose reduction of rituximab in relapsing–remitting multiple sclerosis

2021 ◽  
Author(s):  
Malin Boremalm ◽  
Peter Sundström ◽  
Jonatan Salzer
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Dose Reduction ◽  
Inflammatory Disease ◽  
University Hospital ◽  
Full Dose ◽  
Reduced Dose ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Abstract Background Rituximab is safe and effective for treating relapsing–remitting multiple sclerosis (RRMS) according to phase II and observational studies. There are limited data on disease activity after discontinuation and dose reduction. The objective of this study was to evaluate the effects on inflammatory disease activity after discontinuation or dose reduction of rituximab in patients with RRMS or clinically isolated syndrome (CIS). Methods In this retrospective observational study, we included all RRMS and CIS patients ever treated with rituximab at the University Hospital of Umeå who had either; (1) discontinued treatment at any time or (2) reduced the dose to a mean of < 1000 mg yearly. The patients served as their own controls by contributing patient years on full dose, reduced dose, and off treatment. Results A total of 225 patients treated with mean (SD) 6256 (2456) mg rituximab during mean (SD) 6.5 (2.0) years were included. There were no differences regarding the annualized relapse rates during full dose versus reduced dose or off treatment (0.02 versus < 0.01 and 0.02, p = 0.09), neither regarding proportion MRI scans with new or enlarged T2 lesions (0.03 versus 0.01 and 0.03, p = 0.37) or contrast-enhancing lesions (< 0.01 versus 0 and 0.02, p = 0.22). Conclusions This study indicates that rituximab has long-term effects on inflammatory disease activity and that disease reactivation is rare in MS patients who discontinued treatment for any reason. It also suggests that treatment with low-dose rituximab (< 1000 mg yearly) is sufficient to maintain suppression of inflammatory disease activity in patients with stable disease.

scholarly journals A comparative study of teriflunomide and dimethyl fumarate within the Swedish MS Registry

2021 ◽  
pp. 135245852110196
Author(s):  
Jan Hillert ◽  
Jon A Tsai ◽  
Mona Nouhi ◽  
Anna Glaser ◽  
Tim Spelman
Keyword(s):  
Multiple Sclerosis ◽  
Real World ◽  
Clinical Effectiveness ◽  
Dimethyl Fumarate ◽  
Population Based ◽  
Life Outcomes ◽  
Treatment Persistence ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

Background: Teriflunomide and dimethyl fumarate (DMF) are first-line disease-modifying treatments for multiple sclerosis with similar labels that are used in comparable populations. Objectives: The objective of this study was to compare the effectiveness and persistence of teriflunomide and DMF in a Swedish real-world setting. Methods: All relapsing-remitting multiple sclerosis (RRMS) patients in the Swedish MS registry initiating teriflunomide or DMF were included in the analysis. The primary endpoint was treatment persistence. Propensity score matching was used to adjust comparisons for baseline confounders. Results: A total of 353 teriflunomide patients were successfully matched to 353 DMF. There was no difference in the rate of overall treatment discontinuation by treatment group across the entire observation period (hazard ratio (HR) = 1.12; 95% confidence interval (CI) = 0.91–1.39; p = 0.277; reference = teriflunomide). Annualised relapse rate (ARR) was comparable ( p = 0.237) between DMF (0.07; 95% CI = 0.05–0.10) and teriflunomide (0.09; 95% CI = 0.07–0.12). There was no difference in time to first on-treatment relapse (HR = 0.78; 95% CI = 0.50–1.21), disability progression (HR = 0.55; 95% CI = 0.27–1.12) or confirmed improvement (HR = 1.17; 95% CI = 0.57–2.36). Conclusion: This population-based real-world study reports similarities in treatment persistence, clinical effectiveness and quality of life outcomes between teriflunomide and dimethyl fumarate.

scholarly journals Dimethyl fumarate for relapsing-remitting multiple sclerosis

2014 ◽  
Vol 13 (11) ◽  
pp. 1077-1078
Author(s):  
Martyn J Burke ◽  
Joanna Richardson ◽  
Elisabeth George ◽  
Amanda I Adler
Keyword(s):  
Multiple Sclerosis ◽  
Dimethyl Fumarate ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Do Different Roles of Anesthesia Residents Improve Knowledge Retention after Non-Technical Skills Workshop?

2021 ◽  
Vol 104 (9) ◽  
pp. 1519-1527
Keyword(s):  
Test Scores ◽  
Linear Regression Analysis ◽  
Technical Skills ◽  
Knowledge Retention ◽  
University Hospital ◽  
Multivariate Linear Regression Analysis ◽  
Simulation Based ◽  
Post Test ◽  
Anesthesia Residents ◽  
Predictors Of Change

Objective: The authors assessed whether anesthesia residents who acted as a scenario creators would have better knowledge retention than their juniors 90 days after participating in a simulation-based anesthetists’ non-technical skills (ANTS) workshop. Materials and Methods: A prospective observational study via simulation ANTS workshop was conducted at a university hospital in southern Thailand in November 2017. Seven third-year post-graduate (PGY-3) residents volunteered as scenario creators, while the remaining anesthesia residents were randomly selected to participate in or observe three case scenarios, which were cardiac arrest, hypotension, and difficult ventilation. Resident’s knowledge was assessed before, immediately after, and 90 days after the workshop using a 20-item multiple-choice questionnaire. Predictors of change in knowledge scores were analyzed using multivariate linear regression analysis and presented as beta coefficient (β) and 95% confidence limits (CL). Results: Twenty-four anesthesia residents were recruited in the present study and included eight PGY-1, seven PGY-2, and nine PGY-3. The roles consisted of seven scenario creators, seven participants, and 10 observers. The overall immediate post-test and 90-day post-test scores increased significantly compared to the pre-test scores with a mean of 15.5 and 13.2 versus 11.7 (p<0.001 and p=0.007, respectively). The predictors of change in 90-day scores were PGY-3 versus PGY-1 (β 95% CL 4.0 [0.5 to 7.6], p=0.039), and role of participants and observers versus scenario creator (β 95% CL 5.5 [2.2 to 8.8] and 6.7 [2.8 to 10.6], p=0.004, respectively). Conclusion: Anesthesia residents who were participants or observers could improve their knowledge 90 days after a simulation-based ANTS workshop without necessarily being a scenario creator. Keywords: Anesthetists’ non-technical skill; Knowledge retention; Scenario creator; Simulation workshop

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