Disease Modifying Therapies: Do They Modify Short- and Long-Term in Multiple Sclerosis?

There is no question that disease modifiers reduce inflammation in multiple sclerosis, but do they slow long-term progression of the disease?

To provide an answer, my colleagues and I examined records from patients treated at 3 MS centers in Italy, using a new predictive model for MS progression.¹ Here is a brief synopsis of key clinical findings.

Why was a new study of the effects of biological modifiers on MS progression necessary?
The beneficial effect of immune therapies-the so-called disease modifying therapies (DMTs)-in patients with MS has been largely proved by several studies that analyzed short- and medium-term outcomes, such as relapse rate or changes of disability. However, only a few post-marketing studies have reported data about the efficacy of DMTs in slowing the long-term progression of the disease. Observational studies that can be used to gauge long-term outcomes are affected by several biases, including the lack of blindness and randomization. It was therefore necessary to develop a new approach to evaluate the effectiveness of DMTs in modifying the long-term evolution of MS.

How did this study address these problems?
We applied a particular statistical approach to address the problems that affected the observational studies by grouping patients with a similar likelihood of experiencing unfavorable disease evolution (ie, reaching secondary progression). We calculated a risk score (BREMS) based on the patient’s “natural” propensity for a good or bad prognosis that minimized selection bias and confounding factors due to lack of randomization.

Who participated in the study?
We analyzed 1178 patients with MS; 70% were females; median age at disease onset was 25 years; and median disease duration was 17 years. Patients came from 3 MS centers in Italy. Inclusion criteria included:
• Diagnosis of definite MS according to Poser’s criteria
• Initial relapsing remitting (RRMS) course
• Disease duration 10 years or longer
• Time interval from clinical onset to the first neurological examination 1 year or less

Data from 19,401 person-years were analyzed pre-progression. A total of 143 patients (12%) reached secondary progression within 10 years, as did 376 patients (32%) by the end of the entire observation. The median time to secondary progression was 12 years. Considering only pre-progression treatments that lasted longer than 3 months, 700 patients (60%) were treated with at least 1 immune therapy.

What were the key findings?
We confirmed that DMTs significantly modify the prognosis of MS-short- and long-term. The risk to reach secondary progression was significantly lower among patients treated with DMTs, regardless of the initial risk of poor prognosis.

DMTs benefit not only patients who have a high risk of naturally experiencing unfavorable disease evolution, but also patients who are expected to accumulate only a mild disability.

What are the implications for clinical management of patients with MS?
The recent introduction of new compounds such as natalizumab and fingolimod, which are significantly more powerful than DMTs in reducing clinical and MRI activity, might lead to downplay the advantages of “traditional” immunomodulatory treatments. However, the safety profile of these new drugs has yet to be fully defined. Therefore, the finding that DMTs can positively affect the long-term evolution of MS is of critical importance for patients with MS.

If a BREMS risk score were calculated for each patient, we could reserve very efficient but relatively unsafe therapies for high risk patients, and “classic” DMT for the remainder.

For a pdf of this study, please click here.

Reference
1. Bergamaschi R, Quaglini S, Tavazzi E, et al. Immunomodulatory therapies delay disease progression in multiple sclerosis. Mult Scler J. 2012 May 31; [Epub ahead of print].