scholarly journals No evidence for loss of natalizumab effectiveness with every-6-week dosing: a propensity score–matched comparison with every-4-week dosing in patients enrolled in the Tysabri Observational Program (TOP)

2021 ◽  
Vol 14 ◽  
pp. 175628642110424
Author(s):  
Helmut Butzkueven ◽  
Ludwig Kappos ◽  
Tim Spelman ◽  
Maria Trojano ◽  
Heinz Wiendl ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Propensity Score ◽  
Confidence Interval ◽  
Hazard Ratio ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Matched Comparison ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Observational Program ◽  
Relapse Rates

Background: Extended interval dosing of natalizumab is associated with significantly lower progressive multifocal leukoencephalopathy risk compared with every-4-week (Q4W) dosing in patients with relapsing-remitting multiple sclerosis. Previous studies have suggested that natalizumab effectiveness is maintained in patients who switch from Q4W to extended interval dosing but have been limited by a lack of well-matched patient cohorts. Methods: Tysabri Observational Program (TOP) data as of November 2019 were used to identify patients with relapsing-remitting multiple sclerosis treated with natalizumab Q4W and those with a single physician-indicated dosing change from Q4W to every-6-week (Q6W) dosing after ⩾1 year of Q4W treatment. Patients were propensity score matched at the time of the switch from Q4W to Q6W dosing. Clinical outcomes (annualized relapse rate and probability of remaining relapse free or free of 24-week confirmed disability worsening) and safety outcomes were assessed for the two cohorts. Results: This study included 219 pairs of propensity score–matched Q6W and Q4W patients. Annualized relapse rates were similar for Q6W (0.150) and Q4W (0.157) patients. The probability of remaining relapse free [hazard ratio = 1.243 (95% confidence interval = 0.819–1.888); p = 0.307] and of remaining free of 24-week confirmed disability worsening [hazard ratio = 0.786 (95% confidence interval = 0.284–2.176); p = 0.644] did not differ significantly between Q6W and Q4W patients. Summarized safety results for the matched Q6W and Q4W patients are also presented. Conclusion: These real-world findings in well-matched patient cohorts from TOP demonstrate that natalizumab effectiveness is maintained in patients who switch to Q6W dosing after ⩾1 year of Q4W dosing. ClinicalTrials.gov identifier: NCT00493298

Comparison of fingolimod, dimethyl fumarate and teriflunomide for multiple sclerosis

2019 ◽  
Vol 90 (4) ◽  
pp. 458-468 ◽  
Author(s):  
Tomas Kalincik ◽  
Eva Kubala Havrdova ◽  
Dana Horakova ◽  
Guillermo Izquierdo ◽  
Alexandre Prat ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Propensity Scores ◽  
Negative Binomial ◽  
Dimethyl Fumarate ◽  
Survival Models ◽  
Treatment Persistence ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Relapse Rates

ObjectiveOral immunotherapies have become a standard treatment in relapsing-remitting multiple sclerosis. Direct comparison of their effect on relapse and disability is needed.MethodsWe identified all patients with relapsing-remitting multiple sclerosis treated with teriflunomide, dimethyl fumarate or fingolimod, with minimum 3-month treatment persistence and disability follow-up in the global MSBase cohort study. Patients were matched using propensity scores. Three pairwise analyses compared annualised relapse rates and hazards of disability accumulation, disability improvement and treatment discontinuation (analysed with negative binomial models and weighted conditional survival models, with pairwise censoring).ResultsThe eligible cohorts consisted of 614 (teriflunomide), 782 (dimethyl fumarate) or 2332 (fingolimod) patients, followed over the median of 2.5 years. Annualised relapse rates were lower on fingolimod compared with teriflunomide (0.18 vs 0.24; p=0.05) and dimethyl fumarate (0.20 vs 0.26; p=0.01) and similar on dimethyl fumarate and teriflunomide (0.19 vs 0.22; p=0.55). No differences in disability accumulation (p≥0.59) or improvement (p≥0.14) were found between the therapies. In patients with ≥3-month treatment persistence, subsequent discontinuations were less likely on fingolimod than teriflunomide and dimethyl fumarate (p<0.001). Discontinuation rates on teriflunomide and dimethyl fumarate were similar (p=0.68).ConclusionThe effect of fingolimod on relapse frequency was superior to teriflunomide and dimethyl fumarate. The effect of the three oral therapies on disability outcomes was similar during the initial 2.5 years on treatment. Persistence on fingolimod was superior to the two comparator drugs.

scholarly journals Comparative analysis of dimethyl fumarate and fingolimod in relapsing–remitting multiple sclerosis

2020 ◽  
Author(s):  
Johannes Lorscheider ◽  
Pascal Benkert ◽  
Carmen Lienert ◽  
Peter Hänni ◽  
Tobias Derfuss ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Dimethyl Fumarate ◽  
Oral Disease ◽  
Relapsing Remitting ◽  
Treatment Naïve ◽  
Baseline Characteristics ◽  
Remitting Multiple Sclerosis ◽  
Incident Rate ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Relapse Rates

Abstract Background Dimethyl fumarate and fingolimod are oral disease modifying treatments (DMTs) that reduce relapse activity and slow disability worsening in relapsing–remitting multiple sclerosis (RRMS). Objective To compare the effectiveness of dimethyl fumarate and fingolimod in a real-world setting, where both agents are licensed as a first-line DMT for the treatment of RRMS. Methods We identified patients with RRMS commencing dimethyl fumarate or fingolimod in the Swiss Federation for Common Tasks of Health Insurances (SVK) Registry between August 2014 and July 2019. Propensity score-matching was applied to select subpopulations with comparable baseline characteristics. Relapses and disability outcomes were compared in paired, pairwise-censored analyses. Results Of the 2113 included patients, 1922 were matched (dimethyl fumarate, n = 961; fingolimod, n = 961). Relapse rates did not differ between the groups (incident rate ratio 1.0, 95%CI 0.8–1.2, p = 0.86). Moreover, no difference in the hazard of 1-year confirmed disability worsening (hazard ratio [HR] 0.9; 95%CI 0.6–1.6; p = 0.80) or disability improvement (HR 0.9; 95%CI 0.6–1.2; p = 0.40) was detected. These findings were consistent both for treatment-naïve patients and patients switching from another DMT. Conclusion Dimethyl fumarate and fingolimod have comparable effectiveness regarding reduction of relapses and disability worsening in RRMS.

Real-world disability improvement in patients with relapsing–remitting multiple sclerosis treated with natalizumab in the Tysabri Observational Program

2020 ◽  
pp. 135245852092686
Author(s):  
Heinz Wiendl ◽  
Tim Spelman ◽  
Helmut Butzkueven ◽  
Ludwig Kappos ◽  
Maria Trojano ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Functional System ◽  
Functional Improvement ◽  
Cumulative Probability ◽  
Relapsing Remitting ◽  
Edss Score ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Observational Program

Background: Natalizumab has been associated with disability improvement as indicated by a confirmed Expanded Disability Status Scale (EDSS) score decrease. Objective: The aim of this study was to characterize disability improvement in patients in the Tysabri Observational Program (TOP), an ongoing observational study of relapsing–remitting multiple sclerosis patients initiating natalizumab in clinical practice. Methods: TOP data as of November 2018 were included. Confirmed disability improvement (CDI) was defined as a decrease ⩾1.0 confirmed 24 weeks later from a baseline EDSS score ⩾2.0. Confirmed functional system (FS) improvement was defined as a decrease ⩾1.0 confirmed 24 weeks later from a baseline score ⩾1.0 in that FS. Results: Of 5384 patients, 1287 (23.9%) had CDI; 51.8% experienced CDI in the first treatment year. Among patients with CDI, 56.6% had CDI ⩾1.5 points; 34.4% had CDI ⩾2.0 points. The cumulative probability of maintaining improvement 8 years after the CDI event was 52.6%. At treatment initiation, 5363 patients (85.2%) had impairment in ⩾1 FS. At 8 years, the cumulative probability of confirmed improvement in any FS was 88.8% and ranged from 38.3% to 58.6% in individual FS. Conclusion: These results highlight disability improvement as a potential benefit of natalizumab treatment. Improvements across all FS demonstrate the range of functional improvement.

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