I was pleased by the interest that my last post about the course of MS has generated – the article was shared quite often and there have not been so many comments shortly after going online for quite some time. The comments were also very emotional, which shows that the topic moves many affected people.Emotions are understandable, sensible information, especially for those who are looking for orientation in my blog, is helpful. Therefore, I would like to explain the topic in more detail and substantiate my statements. DocBlog should not be a scientific treatise, so I usually refrain from referencing my statements in my posts – after all, my main concern is to present my approaches in a short, easily understandable form. In this case, I am happy to make an exception.
How do we know how untreated MS progresses?
We generally refer to a cohort published in the renowned British journal Brain in 1989 (Weinshenker BG, Bass B, Rice GP, Noseworthy J, Carriere W, Baskerville J, Ebers GC. The natural history of multiple sclerosis: a geographically based study. I. Clinical course and disability. Brain. 1989 Feb;112 ( Pt 1):133-46. http://www.ncbi.nlm.nih.gov/pubmed/2917275). The authors have examined the clinical course of more than 1,000 untreated patients in great detail and were able to show that after an observation period of 6-10 years, about 30 – 40% of initially relapsing patients have turned into a secondary chronic progressive course. On average, the patients of this cohort reached an EDSS 6 after 15 years (necessity of a one-sided walking aid). The authors were also able to show in the analysis of the cohort that the relapse rate in the first two years after diagnosis significantly correlates with the probability of reaching an EDSS of 6. These important surveys on the natural course of MS were funded by the Canadian MS Society.
Our basic assumptions about the course of untreated MS are based on this and other studies on the natural course of MS:
1) over 80% of MS patients show a relapsing onset
2) over 50% of patients develop a secondary progressive course after 10 years
3) approx. 45% are retired early within 10 years
4) up to 65% of patients develop cognitive impairments
Even if it is occasionally reported by individual patients that MS has not “gone so badly”, it must be assumed in view of the relatively good data situation for the majority of patients that untreated MS leads to problems in the long term.
Does immunomodulatory treatment offer an advantage?
There are meaningful studies on this. As long observation periods are needed to answer the question, most of the surveys on the long-term effect of interferon preparations and Copaxone, which have a moderate effect strength (compared to newer therapies), exist.
In 2007, an Italian group of authors published a paper on the long-term effect of interferon-beta in relapsing MS patients in Annals of Neurology, a renowned American newspaper (Ann Neurol. 2007 Apr;61(4):300-6. Trojano M, Pellegrini F, Fuiani A, Paolicelli D, Zipoli V, Zimatore GB, Di Monte E, Portaccio E, Lepore V, Livrea P, Amato MP. New natural history of interferon-beta-treated relapsing multiple sclerosis. Ann Neurol. 2007 Apr;61(4):300-6. http://www.ncbi.nlm.nih.gov/pubmed/17444502 – the entire article is also freely available).
The analysis of a cohort of 1,504 relapsing MS patients (1,103 IFN-beta-treated and 401 untreated) over a period of 7 years shows a statistically highly significant reduction in the transition to secondary chronic progressive MS and also a highly significant delay in reaching EDSS 4 and 6 in treated patients compared to untreated patients. The study was financed by the Italian Ministry of Health and carried out independently of the pharmaceutical industry.
Does early immunomodulatory treatment offer an advantage?
A study financed by the Italian Ministry of Health with over 2,700 relapsing MS patients in 15 MS centres on the question of the effect of early versus late therapy with interferon-beta also exists (Trojano et al. Real-life impact of early interferon beta therapy in relapsing multiple sclerosis. Ann Neurol. 2009 Oct;66(4):513-20. http://www.ncbi.nlm.nih.gov/pubmed/19847899). Early therapy, in contrast to later given therapy, led to a significant prevention of disease progression and delay in reaching EDSS 4 and EDSS 6 – the observation period was also 7 years.
In addition, there are numerous publications on the long-term course of the study cohorts from the approval studies of all MS drugs – in some cases, data with follow-up periods of over 20 years exist. All studies consistently show that the above-mentioned natural course of MS is significantly modulated – a smaller transition to SPMS and less disability is seen than would be expected from the natural course – the exposure time of the drugs correlates with the effect (i.e. the longer, the better).
The registry studies on more modern and highly effective drugs show on average an even significantly higher improvement of the EDSS values in the long term and a lack of EDSS progression. However, these data are only based on an observation period of 4 years. (Wiendl et al. Epoch Analysis of On-Treatment Disability Progression Events over Time in the Tysabri Observational Program (TOP). PLoS One. 2016 Jan 15;11(1):e0144834. – http://www.ncbi.nlm.nih.gov/pubmed/26771747 – Article freely available)
So one can certainly say that the data situation now clearly speaks for an early and consistent/effective therapy – also with regard to the long-term course of the disease.
