Abstract
Background
Because multiple sclerosis (MS) is a chronic disease causing disability over decades it is crucial to know if the short-term effects of disease modifying therapies reported in randomised controlled trials reduce long-term disability. This 10 year prospective observational study of disability outcomes (EDSS and utility) was set up, in conjunction with a risk-sharing agreement between payers and producers, to investigate this issue.
Methods
The outcomes of the UK treated patients were compared to a modelled untreated control based on the British Columbia MS dataset to assess the long-term effectiveness of these treatments. Two complementary analysis models were used: a multi-level model (MLM) and a continuous Markov Model.
Results
4862 MS patients were eligible for the primary analysis (mean and median follow-up times 8.7 and 10 years)
EDSS worsening was reduced by 28% (MLM), 7% (Markov), 24 % time adjusted Markov in the total cohort, and by 31% (MLM), 14% (Markov), for RR patients. The utility worsening was reduced by 23-24%% in the total cohort, and by 24%-31% RR patients depending on the model used. All sensitivity analyses showed a treatment effect. There was a 4 year (CI 2.7, 5.3) delay to EDSS 6.0. An apparent waning of treatment effect with time was seen. Subgroup analyses suggested better treatment effects in those treated earlier and with lower EDSS scores.
Conclusions
This study supports a beneficial effect on long-term disability with first-line MS DMTs which is clinically meaningful. However the waning effect noted requires further study.
Because multiple sclerosis (MS) is a chronic disease causing disability over decades it is crucial to know if the short-term effects of disease modifying therapies reported in randomised controlled trials reduce long-term disability. This 10 year prospective observational study of disability outcomes (EDSS and utility) was set up, in conjunction with a risk-sharing agreement between payers and producers, to investigate this issue.
Methods
The outcomes of the UK treated patients were compared to a modelled untreated control based on the British Columbia MS dataset to assess the long-term effectiveness of these treatments. Two complementary analysis models were used: a multi-level model (MLM) and a continuous Markov Model.
Results
4862 MS patients were eligible for the primary analysis (mean and median follow-up times 8.7 and 10 years)
EDSS worsening was reduced by 28% (MLM), 7% (Markov), 24 % time adjusted Markov in the total cohort, and by 31% (MLM), 14% (Markov), for RR patients. The utility worsening was reduced by 23-24%% in the total cohort, and by 24%-31% RR patients depending on the model used. All sensitivity analyses showed a treatment effect. There was a 4 year (CI 2.7, 5.3) delay to EDSS 6.0. An apparent waning of treatment effect with time was seen. Subgroup analyses suggested better treatment effects in those treated earlier and with lower EDSS scores.
Conclusions
This study supports a beneficial effect on long-term disability with first-line MS DMTs which is clinically meaningful. However the waning effect noted requires further study.
| Original language | English |
|---|---|
| Number of pages | 10 |
| Journal | Journal of Neurology, Neurosurgery, and Psychiatry |
| Early online date | 21 Sept 2018 |
| DOIs | |
| Publication status | E-pub ahead of print - 21 Sept 2018 |