Discontinuing disease-modifying therapy in MS after a prolonged relapse-free period: a propensity score-matched study

Kister, Ilya; Spelman, Tim; Alroughani, Raed; Lechner‐Scott, Jeannette; Duquette, Pierre; Grand’Maison, François; Slee, Mark; Lugaresi, Alessandra; Barnett, Michael; Grammond, Pierre; Iuliano, Gerardo; Hupperts, Raymond; Pucci, Eugenio; Trojano, María; Butzkueven, Helmut

doi:10.1136/jnnp-2016-313760

Cited by 82 publications

(71 citation statements)

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“…There was a longer time to disability progression in the group of participants who continued treatment than in those who discontinued (HR = 1.47, 95% CI: 1.18-1.84; p = 0.001). 142 Quality assessment. According to the Cochrane tool for 'ROBINS-I', the study was judged to have a moderate risk of bias overall.…”

Section: R16mentioning

confidence: 99%

“…After a full-text review, one study was excluded, and only one prospective cohort study met the eligibility criteria. 142 It included patients treated with interferon or glatiramer acetate for at least 3 years without relapses for at least 5 years and compared those patients who stopped versus those who continued treatment using propensity score matching. At the study baseline, the mean age was 44 years, and the mean EDSS score was 3.5.…”

Section: R16mentioning

confidence: 99%

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ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis

et al. 2018

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Background and scopeMultiple sclerosis (MS) is an inflammatory-demyelinating disease of the central nervous system (CNS) that is characterized by inflammation, demyelination and degenerative changes. MS usually begins around the age between 20 and 40 years and affects two to three times as many women as men; it also constitutes the most frequent cause of non-traumatic disability in the young adult population. 1 The incidence of MS varies across regions, with rates as high as 8 to 10 new cases per 100,000 in high latitudinal regions. 2,3 Current estimates suggest that over 700,000 people are affected in Europe, with over 2.5 million cases worldwide, 4 which represent a significant burden in terms of impact on quality of life, societal costs and personal expenses. 5,6 Most patients (85%-90%) have a relapsing course from onset that is characterized by relapses and remissions of neurological symptoms Methods: This guideline has been developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology and following the updated EAN recommendations. Clinical questions were formulated in Patients-Intervention-Comparator-Outcome (PICO) format and outcomes were prioritized. The quality of evidence was rated into four categories according to the risk of bias. The recommendations with assigned strength (strong and weak) were formulated based on the quality of evidence and the risk-benefit balance. Consensus between the panelists was reached by use of the modified nominal group technique. Results: A total of 10 questions were agreed, encompassing treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns and treatment strategies in MS and pregnancy. The guideline takes into account all disease-modifying drugs approved by the European Medicine Agency (EMA) at the time of publication. A total of 21 recommendations were agreed by the guideline working group after three rounds of consensus. Conclusion:The present guideline will enable homogeneity of treatment decisions across Europe. associated with areas of CNS inflammation, and over the course of two decades, more than half of untreated patients transition to a phase of gradual worsening independent of acute attacks. 7,8 Progressive forms of MS can be present as the initial disease course (primary-progressive MS) in approximately 10%-15% of patients. 9,10 There is no curative treatment available for MS, and the current therapeutic strategy is aimed at reducing the risk of relapses and potentially disability progression. The treatment era for MS began in 1993, when the first interferon became available, and recent years have seen a large expansion in the therapeutic options for MS, with 11 disease-modifying therapies (DMTs) approved by the European Medicine Agency (EMA) in both injectable and oral formulations by the beginning of 2017. 11 The growing armamentarium of therapies brings new opportunities for individualized therapy where patients and providers must balance considerations around efficacy,...

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Section: R16mentioning

confidence: 99%

Section: R16mentioning

confidence: 99%

ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis

et al. 2018

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“…Similarly, the highest cumulative exposure (a parameter including both dosage and time) to Interferon beta-1a treatment had more beneficial effects on long-term outcomes, compared to the lowest, in patients with similar baseline clinical features [6]. Accordingly, the discontinuation of DMTs in patients with a more benign evolution determined a progressive disability accrual after 5 years, compared with subjects staying on continuous treatment with a more aggressive treatment approach [29]. Overall, clinical evidence support the effectiveness of highly-active, continuous and, subsequently, costly treatments seem in preventing or, at least, delaying MS progression.…”

Section: Discussionmentioning

confidence: 99%

Healthcare Costs for Treating Relapsing Multiple Sclerosis and the Risk of Progression: A Retrospective Italian Cohort Study from 2001 to 2015

et al. 2017

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BackgroundDisease modifying treatments (DMTs) are the main responsible for direct medical costs in multiple sclerosis (MS). The current investigation aims at evaluating possible associations between healthcare costs for treating relapsing remitting MS (RRMS) and disease evolution.MethodsThe present cohort study retrospectively included 544 newly diagnosed RRMS patients, prospectively followed up for 10.1±3.3 years. Costs for DMT administration and management were calculated for each year of observation. Following clinical endpoints were recorded: time to first relapse, 1-point EDSS progression, reaching of EDSS 4.0, reaching of EDSS 6.0, and conversion to secondary progressive MS (SP). Covariates for statistical analyses were age, gender, disease duration and EDSS at diagnosis.ResultsAt time varying Cox regression models, 10% increase in annual healthcare costs was associated with 1.1% reduction in 1-point EDSS progression (HR = 0.897; p = 0.018), with 0.7% reduction in reaching EDSS 6.0 (HR = 0.925; p = 0.030), and with 1.0% reduction in SP conversion (HR = 0.902; p = 0.006).ConclusionHigher healthcare costs for treating MS have been associated with a milder disease evolution after 10 years, with possible reduction of long-term non-medical direct and indirect costs.

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“…Rituximab for relapsing MS Three Class II studies [36][37][38] and several large observational studies 39,40 Leflunomide for relapsing MS No published studies RCT of leflunomide vs teriflunomide…”

Section: Use Off-label Drugs As Dmts In Msmentioning

confidence: 99%

“…A recent observational study compared the risk of relapse and disease progression among patients with no relapses for 5 years or more, some of whom stopped DMT and others who continued on DMT. 40 The 2 groups were propensity score-matched from a large MS database, MSBase. Their average age was 45 years.…”

Section: Should Dmts Be Continued Indefinitely?mentioning

confidence: 99%

Reducing costs while enhancing quality of care in MS

Kister

Corboy

2016

Neurology

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The rapid escalation in prices of disease-modifying therapies (DMTs) for multiple sclerosis (MS) over the past decade has resulted in a dramatic overall increase in the costs of MS-related care. In this article, we outline various approaches whereby neurologists can contribute to responsible cost containment while maintaining, and even enhancing, the quality of MS care. The premise of the article is that clinicians are uniquely positioned to introduce innovative management strategies that are both medically sound and cost-efficient. We describe our "top 5" recommendations, including strategies for customizing relapse treatment; developing alternative dosing schedules for Food and Drug Administration-approved MS DMTs; using off-label therapies for relapse suppression; and limiting the use of DMTs to those who clearly fulfill diagnostic criteria, and who might benefit from continued use over time. These suggestions are well-grounded in the literature and our personal experience, but are not always supported with rigorous Class I evidence as yet. We advocate for neurologists to take a greater role in shaping clinical research agendas and helping to establish cost-effective approaches on a firm empiric basis. Neurology ® 2016;87:1617-1622 GLOSSARY DMT 5 disease-modifying therapy; FDA 5 Food and Drug Administration; MS 5 multiple sclerosis; PML 5 progressive multifocal leukoencephalopathy; UBO 5 unidentified bright object.

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Discontinuing disease-modifying therapy in MS after a prolonged relapse-free period: a propensity score-matched study

Abstract: Patients with MS who discontinued injectable DMT after a long period of relapse freedom had a similar relapse rate as propensity score-matched patients who continued on DMT, but higher hazard for disability progression.

Cited by 82 publications

References 20 publications

ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis

ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis

Healthcare Costs for Treating Relapsing Multiple Sclerosis and the Risk of Progression: A Retrospective Italian Cohort Study from 2001 to 2015

Reducing costs while enhancing quality of care in MS

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