Epub: Bergamaschi R et al. Immunomodulatory therapies delay disease progression in multiple sclerosis.Mult Scler. 2012 May 31.
BACKGROUND: Few studies have analysed long-term effects of immunomodulatory disease modifying drugs (DMDs).
OBJECTIVE: Assessment of the efficacy of DMDs on long-term evolution of multiple sclerosis, using a Bayesian approach to overcome methodological problems related to open-label studies.Methods: MS patients from three different Italian multiple sclerosis centres were divided into subgroups according to the presence of treatment in their disease history before the endpoint, which was represented by secondary progression. Patients were stratified on the basis of the risk score BREMS (Bayesian risk estimate for multiple sclerosis), which is able to predict the unfavourable long-term evolution of MS at an early stage.
RESULTS: We analysed data from 1178 patients with a relapsing form of multiple sclerosis at onset and at least 10 years of disease duration, treated (59%) or untreated with DMDs. The risk of secondary progression was significantly lower in patients treated with DMDs, regardless of the initial prognosis predicted by BREMS.Conclusions: DMDs significantly reduce the risk of multiple sclerosis progression both in patients with initial high-risk and patients with initial low-risk. These findings reinforce the role of DMDs in modifying the natural course of the disease, suggesting that they have a positive effect not only on the inflammatory but also on the neurodegenerative process. The study also confirms the capability of the BREMS score to predict MS evolution.
However we also have a conflicting report
Shirani et al. Association between use of interferon Beta and progression of disability in patients with relapsing-remitting multiple sclerosis. . 2012 Jul;308(3):247-56
OBJECTIVE: To investigate the association between interferon beta exposure and disability progression in patients with relapsing-remitting MS.
DESIGN, SETTING, AND PATIENTS: Retrospective cohort study based on prospectively collected data (1985-2008) from British Columbia, Canada. Patients with relapsing-remitting MS treated with interferon beta (n = 868) were compared with untreated contemporary (n = 829) and historical (n = 959) cohorts.
MAIN OUTCOME MEASURES: The main outcome measure was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of 6 (requiring a cane to walk 100 m; confirmed at 150 days with no measurable improvement) on the Expanded Disability Status Scale (EDSS) (range, 0-10, with higher scores indicating higher disability).
RESULTS: The median active follow-up times (first to last EDSS measurement) were as follows: for the interferon beta-treated cohort, 5.1 years (interquartile range [IQR], 3.0-7.0 years); for the contemporary control cohort, 4.0 years (IQR, 2.1-6.4 years); and for the historical control cohort, 10.8 years (IQR, 6.3-14.7 years). The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8%, 5.3%, and 23.1% in the 3 cohorts, respectively. After adjustment for potential baseline confounders (sex, age, disease duration, and EDSS score), exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort (hazard ratio, 1.30; 95% CI, 0.92-1.83; P = .14) or the historical control cohort (hazard ratio, 0.77; 95% CI, 0.58-1.02; P = .07) were considered. Further adjustment for comorbidities and socioeconomic status, where possible, did not change interpretations, and propensity score adjustment did not substantially change the results.
CONCLUSION: Among patients with relapsing-remitting MS, administration of interferon beta was not associated with a reduction in progression of disability
We kind of have heard about this study before because George Ebers has spoken about the effect of interferon on progression and has suggested that relapse rate does not influence progression except early in disease course. However tell that to someone who has had a disabling relapse they they are not relevant.
The two studies have different outcomes and so are not easy to directly compare, but differences in science are commonplace and this is why things are repeated. Eventually one gets consensus. You would have though pharma would collect this type of information, but it may not be the info it wants to hear, so they do not do it.
Prof G says “The problem with the data from the Canadian study is that it is not controlled and hence their will a lot of bias that cannot be taken into account. For example, the untreated contemporary and historical cohorts had a longer disease duration for the same level of disability at baseline; this would imply that they had more benign disease. They would therefore expect to do better than a cohort with more active disease (shorter disease duration for same level of disability). The fact that they did as well as each other to EDSS 6.0 implies that IFNbeta must have been doing something”.
Furthermore Prof G says “The bottom line is IFNbeta is not a very effective treatment; this study confirms this. That doesn’t mean we shouldn’t use it as some MSers respond better than others and in the UK, at least, you have to fail first-line treatments to access the more effect second-line treatments. For this reason alone IFNbeta has many years left in its legs and hence the rush to develop long-acting preparations and cheaper biosimilars. My main worry with them is the legacy NABs to INFbeta will leave behind.”
Let us hope that as we move into the age of more effective treatments that an effect on progression will be clear. I am hopeful that it will.