scholarly journals Effect of Disease Modifying Therapy on Disability in Relapsing-Remitting Multiple Sclerosis Over 15 Years

Neurology ◽  
2020 ◽  
pp. 10.1212/WNL.0000000000011242
Author(s):  
Tomas Kalincik ◽  
Ibrahima Diouf ◽  
Sifat Sharmin ◽  
Charles Malpas ◽  
Tim Spelman ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Structural Models ◽  
Marginal Structural Models ◽  
Multiple Sclerosis Therapy ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

ObjectiveTo test the hypothesis that immunotherapy prevents long-term disability in relapsing-remitting multiple sclerosis, we modelled disability outcomes in 14,717 patients.MethodsWe studied patients from MSBase followed for ≥1 year, with ≥3 visits, ≥1 visit per year and exposed to a multiple sclerosis therapy, and a subset of patients with ≥15-year follow-up. Marginal structural models were used to compare the hazard of 12-month confirmed increase and decrease in disability, EDSS step 6 and the incidence of relapses between treated and untreated periods. Marginal structural models were continuously re-adjusted for patient age, sex, pregnancy, date, disease course, time from first symptom, prior relapse history, disability and MRI activity.Results14,717 patients were studied. During the treated periods, patients were less likely to experience relapses (hazard ratio 0.60, 95% confidence interval 0.43–0.82, p = 0.0016), worsening of disability (0.56, 0.38–0.82, p = 0.0026) and progress to EDSS step 6 (0.33, 0.19–0.59, p = 0.00019). Among 1,085 patients with ≥15-year follow-up, the treated patients were less likely to experience relapses (0.59, 0.50–0.70, p = 10−9) and worsening of disability (0.81, 0.67–0.99, p = 0.043).ConclusionsContinued treatment with multiple sclerosis immunotherapies reduces disability accrual by 19%–44% (95%CI 1%–62%), the risk of need of a walking aid by 67% (95%CI 41%–81%) and the frequency of relapses by 40–41% (95%CI 18%–57%) over 15 years. This study provides the evidence that disease modifying therapies are effective in improving disability outcomes in relapsing-remitting multiple sclerosis over the long-term.Classification of evidenceThis study provides class IV evidence that for patients with relapsing-remitting multiple sclerosis, long-term exposure to immunotherapy prevents neurological disability.

scholarly journals Immunotherapy prevents long-term disability in relapsing multiple sclerosis over 15 years

2019 ◽  
Author(s):  
Tomas Kalincik ◽  
Sifat Sharmin ◽  
Charles Malpas ◽  
Tim Spelman ◽  
Dana Horakova ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Structural Models ◽  
Marginal Structural Models ◽  
Long Term Effect ◽  
Multiple Sclerosis Therapy ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Sclerosis Therapy

ABSTRACTObjectiveWhether immunotherapy improves long-term disability in multiple sclerosis has not been satisfactorily demonstrated. This study examined the effect of immunotherapy on long-term disability outcomes in relapsing-remitting multiple sclerosis.MethodsWe studied patients from MSBase followed for ≥1 year, with ≥3 visits, ≥1 visit per year and exposed to a multiple sclerosis therapy, and a subset of patients with ≥15-year follow-up. Marginal structural models were used to compare the hazard of 12-month confirmed increase and decrease in disability, EDSS step 6 and the incidence of relapses between treated and untreated periods. Marginal structural models were continuously re-adjusted for patient age, sex, pregnancy, date, disease course, time from first symptom, prior relapse history, disability and MRI activity.Results14,717 patients were studied. During the treated periods, patients were less likely to experience relapses (hazard ratio 0.60, 95% confidence interval 0.43–0.82, p=0.0016), worsening of disability (0.56, 0.38-0.82, p=0.0026) and progress to EDSS step 6 (0.33, 0.19-0.59, p=0.00019). Among 1085 patients with ≥15-year follow-up, the treated patients were less likely to experience relapses (0.59, 0.50–0.70, p=10-9) and worsening of disability (0.81, 0.67-0.99, p=0.043).ConclusionsContinued treatment with multiple sclerosis immunotherapies reduces disability accrual (by 19-44%), the risk of need of a walking aid by 67% and the frequency of relapses (by 40-41%) over 15 years. A proof of long-term effect of immunomodulation on disability outcomes is the key to establishing its disease modifying properties.

scholarly journals Reliability in long-term clinical studies of disease-modifying therapies for relapsing-remitting multiple sclerosis: A systematic review

PLoS ONE ◽  
2020 ◽  
Vol 15 (6) ◽  
pp. e0231722 ◽  
Author(s):  
Rosa C. Lucchetta ◽  
Letícia P. Leonart ◽  
Marcus V. M. Gonçalves ◽  
Jefferson Becker ◽  
Roberto Pontarolo ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Systematic Review ◽  
Clinical Studies ◽  
Disease Modifying Therapies ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

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

Switching first-line disease-modifying therapy after failure: impact on the course of relapsing–remitting multiple sclerosis

2009 ◽  
Vol 15 (1) ◽  
pp. 50-58 ◽  
Author(s):  
A Gajofatto ◽  
P Bacchetti ◽  
B Grimes ◽  
A High ◽  
E Waubant
Keyword(s):  
Multiple Sclerosis ◽  
Initial Therapy ◽  
First Line ◽  
Disease Modifying Therapy ◽  
Disease Modifying Therapies ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Background Options for non-responders to relapsing–remitting multiple sclerosis (RRMS) first-line disease-modifying therapies (DMT) are limited. We explored whether switching first-line DMT is effective. Methods Patients with RRMS who first received interferon-beta (IFNB) or glatiramer acetate (GA) were classified in three categories: DMT change because of suboptimal response, DMT change because of other reasons, and no DMT change during follow-up. Outcomes included annualized relapse rate (ARR) and relapse-free proportions. Results We identified 597 patients who initiated first-line DMT. For patients who did not change DMT ( n = 240), pre-DMT and on-DMT median ARR were 0.50 and 0 ( P < 0.0001). At 24 months, 76% (95%CI = 69–81%) of patients who did not change DMT were relapse-free. Of the 155 who switched because of suboptimal response, 101 switched to another first-line DMT. Median ARR pre-DMT, on first DMT and second DMT were: 0.50, 0.55, and 0.25 for switchers from IFNB to GA (IFNB/GA, n = 12) (pre-DMT versus first DMT: P = 0.92; first versus second DMT: P = 0.31); 0.90, 0.50, and 0 for switchers from GA to IFNB (GA/IFNB, n = 18; P = 0.19; P = 0.01); 0.50, 0.68, and 0 for switchers from an IFNB to another IFNB (IFNB/IFNB’, n = 71; P = 0.34; P = 0.02). Estimated relapse-free proportion after 24 months of treatment was 42% (95%CI=15–66%) during the period on IFNB versus 53% (95%CI = 17–80%) on GA for IFNB/GA ( P = 0.21); 12% (95%CI = 0–40%) on GA versus 87% (95%CI = 59–97%) on IFNB for GA/IFNB ( P = 0.001); and 41% (95%CI = 29–52%) on initial IFNB versus 67% (95%CI = 53–79%) on subsequent IFNB for IFNB/IFNB’ ( P = 0.0001). Conclusions Switching first-line DMT in patients with RRMS failing initial therapy may be effective in many cases.

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 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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