Effect of lateral therapy switches to oral moderate-efficacy drugs in multiple sclerosis: a nationwide cohort study

2021 ◽  
pp. jnnp-2020-324869 ◽  
Author(s):  
Mathias Due Buron ◽  
Tomas Kalincik ◽  
Finn Sellebjerg ◽  
Per Soelberg Sørensen ◽  
Melinda Magyari
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Absolute Risk ◽  
Dimethyl Fumarate ◽  
Interferon Β ◽  
First Line ◽  
Disease Modifying Therapies ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

BackgroundSwitching between first-line disease-modifying therapies in patients with clinically stable relapsing–remitting multiple sclerosis (RRMS) due to reasons other than disease activity is frequent, but evidence on the effect of this practice is limited. We investigated the effect of switching patients with stable RRMS on occurrences of disability accumulation, relapses and future treatment discontinuation.MethodsUsing the Danish Multiple Sclerosis Registry, we identified patients with RRMS without disease activity who either (1) stayed on injectable platform therapy (interferon-β or glatiramer acetate) or (2) switched to dimethyl fumarate (DMF) or teriflunomide (TFL) and compared treatment outcomes using propensity-score-based methods and marginal structural models (MSM).ResultsWe included 3206 patients in the study. We found no change in risk of 6-month confirmed Expanded Disability Status Scale score worsening in patients switching to DMF (HR: 1.15, 95% CI 0.88 to 1.50) or TFL (HR: 1.16, 95% CI 0.92 to 1.46). The risk of suffering any relapse tended to decrease when switching to DMF (HR: 0.73, 95% CI 0.51 to 1.04) and tended to increase when switching to TFL (HR: 1.25, 95% CI 0.96 to 1.63). Absolute risk differences were small. MSM analyses showed similar results but did not find an increased relapse risk in TFL switchers.ConclusionSwitching from injectable platform therapies to oral first-line therapies in patients with clinically stable RRMS does not increase the risk of disability accumulation. While the postswitch risk of relapses trended towards marginally higher on TFL, this trend was eliminated by adjustment for time-variant confounders.

Large pipeline and new safety issues likely to change 1st line recommendations for multiple sclerosis

2012 ◽  
Vol 2 (2) ◽  
pp. 32-36
Author(s):  
Gayle Kamm
Keyword(s):  
Multiple Sclerosis ◽  
Neurodegenerative Disorder ◽  
Review Article ◽  
Evidence Based ◽  
First Line ◽  
Safety Issues ◽  
Disease Modifying Therapies ◽  
Relapsing Remitting ◽  
Evidence Based Guidelines ◽  
Relapsing Remitting Multiple Sclerosis

ABSTRACT Multiple Sclerosis (MS) is chronic neurodegenerative disorder which can result in significant morbidity. Currently, there are not evidence-based guidelines for the choice of which first-line agent to start with, when to switch, or what to switch to, when treating MS. This review article discusses recent changes related to the treatment of MS and reviews disease modifying therapies in the pipeline for treatment of 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.

scholarly journals The apparently milder course of multiple sclerosis: changes in the diagnostic criteria, therapy and natural history

Brain ◽  
2020 ◽  
Vol 143 (9) ◽  
pp. 2637-2652 ◽  
Author(s):  
Per Soelberg Sorensen ◽  
Finn Sellebjerg ◽  
Hans-Peter Hartung ◽  
Xavier Montalban ◽  
Giancarlo Comi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Diagnostic Criteria ◽  
Progressive Multiple Sclerosis ◽  
Disease Modifying Therapies ◽  
Relapsing Remitting ◽  
History Of ◽  
Disease Modifying ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Abstract In the past decade, changes have occurred in the spectrum of multiple sclerosis courses. The natural history of multiple sclerosis appears milder from the first sign of demyelinating disease to the progressive course, probably as a result of an interplay between several factors including changes in the diagnostic criteria, changes in the epidemiology of multiple sclerosis, impact of early and appropriate disease-modifying treatment and improvement of the general state of health in the population. It has been suggested to regard incidental findings of demyelinating lesions in MRI in individuals without any history of clinical symptoms consistent with neurological dysfunction, so-called radiological isolated syndrome, as the initial course of multiple sclerosis. New diagnostic criteria have enabled the multiple sclerosis diagnosis in many patients at the first clinical demyelinating event, clinically isolated syndrome. The remaining patients with clinically isolated syndrome have a more benign prognosis, and for relapsing-remitting multiple sclerosis, the prognosis has become more favourable. Reduced disease activity in patients with relapsing-remitting multiple sclerosis can partly be ascribed to more efficacious new disease-modifying therapies but decrease in disease activity has also be seen in placebo-treated patients in clinical trials. This may be explained by several factors: change in the diagnostic criteria, more explicit inclusion criteria, exclusion of high-risk patients e.g. patients with co-morbidities, and more rigorous definitions of relapses and disease worsening. However, these factors also make the disease course in patients treated with disease-modifying therapies seem more favourable. In addition, change in the therapeutic target to stable disease (no evidence of disease activity = no relapses, no disease worsening and no MRI activity) could by itself change the course in relapsing-remitting multiple sclerosis. The effectiveness of disease-modifying drugs has reduced the transition from relapsing-remitting to secondary progressive multiple sclerosis. The concept of progressive multiple sclerosis has also evolved from two very distinct categories (primary progressive and secondary progressive multiple sclerosis) to a unified category of progressive multiple sclerosis, which can then be split into the categories of active or inactive. Also, an increasing tendency to treat progressive multiple sclerosis with disease-modifying therapies may have contributed to change the course in progressive multiple sclerosis. In conclusion, during the past decade the entire course of multiple sclerosis from the first sign of a demyelinating disorder through the progressive course appears to be milder due to a complex interplay of several factors.

Serum levels of IL-17A in patients with relapsing–remitting multiple sclerosis treated with interferon-β

2012 ◽  
Vol 19 (7) ◽  
pp. 885-890 ◽  
Author(s):  
Rodica Bălaşa ◽  
Zoltan Bajko ◽  
Adina Huţanu
Keyword(s):  
Multiple Sclerosis ◽  
Healthy Subjects ◽  
Serum Levels ◽  
High Serum ◽  
Interleukin 17 ◽  
Interferon Β ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Background: Interleukin-17 (IL-17), which is secreted by Th17 cells, is a proinflammatory cytokine that is implicated in the pathogenesis of multiple sclerosis (MS) and plays a role in nonresponse of MS patients to interferon-β (IFN-β) therapy. Objectives: The purpose of this study was to establish a correlation between nonresponders (NR) and IL-17A serum titers and binding antibodies (BAbs) to IFN-β, as well as to find a correlation between IL-17A serum levels and other features of MS patients. Methods: Our prospective study included 72 inactive relapsing–remitting multiple sclerosis (RRMS) patients that had been treated for at least 18 months with IFN-β and 15 healthy subjects. We determined the serum levels of IL-17A and of BAbs. IL-17A levels were considered elevated (IL-17A+) if the recorded value was greater than 1.6 pg/ml. Results: Twenty-seven patients (37.5%) were NR and had a significantly higher serum IL-17A level compared to the responders group. Nineteen patients (26.4%) were IL-17A+ and had had a significantly higher number of relapses in the previous year and a higher Expanded Disability Status Score. The majority of IL-17A+ patients were NR and had a shorter MS duration. Conclusions: RRMS patients with high serum IL-17A levels do not respond well to IFN-β therapy and have shorter MS duration compared to patients with low IL-17A levels. This response is not influenced by the presence of BAbs.

scholarly journals Comparative effectiveness of teriflunomide and dimethyl fumarate

Neurology ◽  
2019 ◽  
Vol 92 (16) ◽  
pp. e1811-e1820 ◽  
Author(s):  
Mathias Due Buron ◽  
Thor Ameri Chalmer ◽  
Finn Sellebjerg ◽  
Jette Frederiksen ◽  
Monika Katarzyna Góra ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Treatment Efficacy ◽  
Dimethyl Fumarate ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

ObjectiveTo compare on-treatment efficacy and discontinuation outcomes in teriflunomide (TFL) and dimethyl fumarate (DMF) in the treatment of relapsing-remitting multiple sclerosis (RRMS) in a real-world setting.MethodsWe identified all patients starting TFL or DMF from the Danish Multiple Sclerosis Registry and compared on-treatment efficacy outcomes between DMF using TFL, adjusted for clinical baseline variables and propensity score-based methods.ResultsWe included 2,236 patients in the study: 1,469 patients on TFL and 767 on DMF. Annualized relapse rates (ARRs) in TFL and DMF were 0.16 (95% confidence interval [CI] 0.13–0.20) and 0.09 (95% CI 0.07–0.12), respectively. Relapse rate ratio for DMF/TFL was 0.58 (95% CI 0.46–0.73, p < 0.001). DMF had a higher relapse-free survival proportion at 48 months of follow-up (p < 0.05). We observed no difference in Expanded Disability Status Scale score worsening. Discontinuations due to disease breakthrough were 10.2% (95% CI 7.6%–12.8%) and 22.1% (95% CI 19.2%–25.0%) for DMF and TFL, respectively. A subgroup analysis of ARRs in 708 patients with available baseline MRI T2 lesion amount reported similar results after adjustment.ConclusionWe found lower ARR, higher relapse-free survival, and lower incidence of discontinuation due to disease breakthrough on treatment with DMF compared with TFL.Classification of evidenceThis study provides Class II evidence that for patients with RRMS, DMF is more effective in preventing relapses and has lower discontinuation due to disease breakthrough compared with TFL.

scholarly journals [Cost-effectiveness analysis of delayed-release dimethyl-fumarate in the treatment of relapsing-remitting multiple sclerosis in Italy]

2016 ◽  
Vol 17 (2) ◽  
pp. 67-80 ◽  
Author(s):  
Gianluca Furneri ◽  
Laura Santoni ◽  
Chiara Marchesi ◽  
Sergio Iannazzo ◽  
Paolo Angelo Cortesi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Sensitivity Analysis ◽  
Cost Effectiveness ◽  
Economic Analysis ◽  
Cost Effective ◽  
Dimethyl Fumarate ◽  
Direct Costs ◽  
First Line ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

INTRODUCTION: Disease Modifying Therapies (DMTs) have significantly improved clinical conditions of Relapsing Remitting Multiple Sclerosis (RRMS) patients. However, several unmet needs are still relevant in RRMS. Recently, a new therapy, delayed-release dimethyl-fumarate (DMF; also known as gastro-resistant DMF), has been approved and reimbursed by the Italian Drug Agency (AIFA) for the treatment of RRMS.OBJECTIVE: To compare the cost-effectiveness of DMF vs. pharmacological alternatives indicated for the first-line treatment of RRMS in Italy.METHODS: The analysis was conducted from the perspective of the Italian National Healthcare Service (NHS) and outcomes and costs were evaluated over a 50-year time horizon (equivalent to a lifetime horizon). Both outcomes and costs were discounted at 3.5%. The Markov model estimates the clinical and economic consequences of treating RRMS patients with the following therapeutic options: DMF, interferon (IFN) beta-1a intramuscular (IM); IFN beta-1a subcutaneous (SC) at two different doses, 22 mcg and 44 mcg; IFN beta-1b SC; glatiramer acetate (GA) SC 20 mg; oral teriflunomide. Clinical efficacy data used in this analysis came from an elaboration of the mixed treatment comparison (MTC) already published. According to the Italian NHS perspective, only the following direct costs were considered: pharmacological treatment acquisition, treatment monitoring, relapse management, direct costs associated with disability, adverse event management. Administration costs were assumed equal to €0, because every treatment included in the economic analysis can be self-administered. One-way and probabilistic sensitivity analyses were developed and cost effectiveness acceptability curves generated.RESULTS: In the base-case analysis, DMF was more efficacious than alternatives, in terms of both survival (19.496 vs. 19.297-19.461 discounted LYs, respectively), and QALYs (6.548 vs. 5.172- 6.212 discounted QALYs, respectively). Per-patient lifetime costs with DMF amounted to € 276,500, similarly to the other options. DMF was the drug with the largest effect of disability cost reduction. DMF was dominant vs. IFN beta-1a 44 mcg and cost-effective vs. all other IFNs, GA and teriflunomide, with incremental cost-effectiveness ratio (ICERs) between € 11,272 and € 23,409. All ICER values were lower than the € 50,000 per QALY threshold. One-way sensitivity analysis showed that, for all tested scenarios, ICER of DMF vs. therapeutic alternatives remained favourable (≤ 50.000 €/QALY gained) and the results of probabilistic sensitivity analysis showed that the probability for DMF of being favourable (≤ 50.000 €/QALY gained) was between around 70% and 93%, thus ensuring robustness of the results.CONCLUSIONS: The results of this economic analysis show that, at the current price and the described assumptions, DMF represents a cost-effective option vs. other available first-line treatments indicated in RRMS in the perspective of the Italian NHS.[Article in Italian]

scholarly journals Іmpact of pathogenic therapy of multiple sclerosis on clinical and neuroimaging factors of its activity

2021 ◽  
pp. 39-42
Author(s):  
T. A. Kobys
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Neuroprotective Effect ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
T2 Lesions ◽  
Line Therapy ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

The article presents the experience of the Kiev Center of Multiple Sclerosis in using pathogenic first-line and second-line therapy to treat patients with relapsing-remitting multiple sclerosis (RRMS). We have analyzed clinical and neuroimaging factors of disease activity (relapse rate, changes in T2 lesions, Gd+ lesions) to assess the efficacy of the treatment during 24 months. Based on the NAA/Cr ratio we determined the neuroprotective effect of the therapy. The significant effect of pathogenic treatment is associated with both decrease in relapse frequency and with a slowdown in the emergence of new T2 and Gd+ lesions.

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