Background

Multiple Sclerosis (MS) is a disorder of the central nervous system characterized by inflammation, demyelination, and degenerative changes. For chronic conditions requiring a potential lifetime of treatment, treatment discontinuation may result in significant clinical issues, including relapse risk and disease progression. There can be a number of factors contributing to treatment discontinuation, but several studies have demonstrated that adverse events and the lack of efficacy represented by continued disease progression are the leading causes. In MS, patient satisfaction with treatment is essential for sustained persistency and positive long-term health outcomes.

Objectives

Understanding the long-term safety and efficacy considerations of a potential treatment in a chronic disease such as MS is critical to both patients and providers. The aim of this analysis is to understand the frequency and reason leading to premature treatment discontinuation from the long-term extension for patients on the 20mg of ponesimod.

Methods

In the main phase 2 study (B201), a total of 464 subjects were randomized in a 1:1:1:1 ratio to receive ponesimod 10 mg (N=108), ponesimod 20 mg (N=116), ponesimod 40 mg (N=119), or placebo (N=121), resulting in a total of 462/464 (99.6%) treated subjects, of whom 393 completed the 24-week double-blind treatment period. Of the 393 subjects who completed treatment in the core study, subjects were eligible to be enrolled into of the extension study (B202) of three treatment phases (TP1, TP2, and TP3) maintaining the either the same dose or for placebo patients rerandomized to 10, 20 or 40mg (although the 40mg was discontinued after TP1).

Results

As of the 31 March 2019 (8.3 years after initiation), a total of 60.7% of subjects in the 20mg arm had maintained therapy on ponesimod over the course of the study and subsequent extensions. For those patients with premature discontinuations, reasons for discontinuation: 40.4% unknown subject decision, 28.1% tolerability/AE related, 17.5% efficacy related, and 14% other reasons.

Conclusions

Patient satisfaction with treatment is key to ensure adherence in a long-term chronic disease. The retention of over 60% of patients during an 8 year, phase 2 long term extension study suggests a high degree of patient satisfaction with the tolerability, safety and efficacy of ponesimod.

Background

Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system that results in progressive and irreversible disability. Fatigue is one of the most common MS-related symptoms and is characterized by a persistent lack of energy that impairs daily functioning. The burden of MS-related fatigue is complex and multidimensional, and to our knowledge, no systematic literature review has been conducted on this subject.

Objectives

To conduct a systematic literature review identifying published data on the quality of life (QoL) and economic burden of fatigue in people with MS.

Methods

Systematic searches were conducted in MEDLINE, Embase, and Evidence-Based Medicine Reviews to identify published studies quantifying the burden of fatigue on QoL and economic outcomes in people with relapsing-remitting MS, secondary progressive MS, and clinically isolated syndrome. English-language articles published from 2010 to January 2020 were included. Studies reporting comparisons between fatigued and non-fatigued people with MS were prioritized as they were most interpretable for understanding the burden of fatigue in MS. Studies assessing associations between outcomes and fatigue as a continuous measure were included to supplement the available data on economic burden due to gaps in the literature.

Results

In the systematic search, 8,147 unique records were identified, of which 19 records met the inclusion criteria. Of the included records comparing fatigued to non-fatigued people with MS, 11 reported QoL outcomes and 9 reported economic outcomes. The supplementary screen for economic studies with fatigue as a continuous measure included 20 records.

The presence of MS-related fatigue was associated with significantly lower QoL on one or more validated scales or subscales in each reviewed QoL study. Results on the economic impact of fatigue were more heterogeneous, but most studies reported a significant association between presence or severity of fatigue and employment status, capacity to work, and sick leave. There is a gap in evidence regarding the direct costs of MS-related fatigue and the financial or QoL burden placed on the caregivers of affected people.

Conclusions

MS-related fatigue is associated with considerable QoL and economic burden. Further studies are needed to better understand the impact of fatigue on direct costs for people with MS and their caregivers.

Background

Multiple Sclerosis (MS) is a disorder of the central nervous system characterized by inflammation, demyelination, and degenerative changes. For chronic conditions requiring a potential lifetime of treatment, treatment discontinuation may result in significant clinical issues, including relapse risk and disease progression. There can be a number of factors contributing to treatment discontinuation, but several studies have demonstrated that adverse events and the lack of efficacy represented by continued disease progression are the leading causes. In MS, patient satisfaction with treatment is essential for sustained persistency and positive long-term health outcomes.

Objectives

Understanding the long-term safety and efficacy considerations of a potential treatment in a chronic disease such as MS is critical to both patients and providers. The aim of this analysis is to understand the frequency and reason leading to premature treatment discontinuation from the long-term extension for patients on the 20mg of ponesimod.

Methods

In the main phase 2 study (B201), a total of 464 subjects were randomized in a 1:1:1:1 ratio to receive ponesimod 10 mg (N=108), ponesimod 20 mg (N=116), ponesimod 40 mg (N=119), or placebo (N=121), resulting in a total of 462/464 (99.6%) treated subjects, of whom 393 completed the 24-week double-blind treatment period. Of the 393 subjects who completed treatment in the core study, subjects were eligible to be enrolled into of the extension study (B202) of three treatment phases (TP1, TP2, and TP3) maintaining the either the same dose or for placebo patients rerandomized to 10, 20 or 40mg (although the 40mg was discontinued after TP1).

Results

As of the 31 March 2019 (8.3 years after initiation), a total of 60.7% of subjects in the 20mg arm had maintained therapy on ponesimod over the course of the study and subsequent extensions. For those patients with premature discontinuations, reasons for discontinuation: 40.4% unknown subject decision, 28.1% tolerability/AE related, 17.5% efficacy related, and 14% other reasons.

Conclusions

Patient satisfaction with treatment is key to ensure adherence in a long-term chronic disease. The retention of over 60% of patients during an 8 year, phase 2 long term extension study suggests a high degree of patient satisfaction with the tolerability, safety and efficacy of ponesimod.

Background

Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system that results in progressive and irreversible disability. Fatigue is one of the most common MS-related symptoms and is characterized by a persistent lack of energy that impairs daily functioning. The burden of MS-related fatigue is complex and multidimensional, and to our knowledge, no systematic literature review has been conducted on this subject.

Objectives

To conduct a systematic literature review identifying published data on the quality of life (QoL) and economic burden of fatigue in people with MS.

Methods

Systematic searches were conducted in MEDLINE, Embase, and Evidence-Based Medicine Reviews to identify published studies quantifying the burden of fatigue on QoL and economic outcomes in people with relapsing-remitting MS, secondary progressive MS, and clinically isolated syndrome. English-language articles published from 2010 to January 2020 were included. Studies reporting comparisons between fatigued and non-fatigued people with MS were prioritized as they were most interpretable for understanding the burden of fatigue in MS. Studies assessing associations between outcomes and fatigue as a continuous measure were included to supplement the available data on economic burden due to gaps in the literature.

Results

In the systematic search, 8,147 unique records were identified, of which 19 records met the inclusion criteria. Of the included records comparing fatigued to non-fatigued people with MS, 11 reported QoL outcomes and 9 reported economic outcomes. The supplementary screen for economic studies with fatigue as a continuous measure included 20 records.

The presence of MS-related fatigue was associated with significantly lower QoL on one or more validated scales or subscales in each reviewed QoL study. Results on the economic impact of fatigue were more heterogeneous, but most studies reported a significant association between presence or severity of fatigue and employment status, capacity to work, and sick leave. There is a gap in evidence regarding the direct costs of MS-related fatigue and the financial or QoL burden placed on the caregivers of affected people.

Conclusions

MS-related fatigue is associated with considerable QoL and economic burden. Further studies are needed to better understand the impact of fatigue on direct costs for people with MS and their caregivers.