Thursday, 16 April 2015

ClinicSpeak: Interferons do not stop the onset of secondary progression

Can we prevent or dealy the onset of SPMS? Not with interferon-beta. #MSBlog #MSResearch #ClinicSpeak

"Analysis of the MSers in the British Columbia MS Register below shows that treatment with interferon-beta did not prevent or delay the onset of SPMS. This data is not consistent with other data sources (MSBase, Italian, French and extension studies). Critics argue that the BC register is an outlier. I am not informed enough to comment. But the data confirms my own clinical impression that on average the majority of MSers on interferon-beta become SP with time. The question that can't be answered here is there a subgroup that does better? Are there responders? Will this study change our practice? Probably no. In an era when our treatment goal has moved to treat-2-target of NEDA we won't leave non-responders or sub-optimal responders on interferon-beta and wait for them to become SP."


Epub: Zhang et al. Beta-interferon exposure and onset of secondary progressive multiple sclerosis. Eur J Neurol. 2015. doi: 10.1111/ene.12698.

BACKGROUND AND PURPOSE: Beta-interferons (IFNβ) are the most widely prescribed drugs for MSers. However, whether or not treatment with IFNβ can delay secondary progressive MS (SPMS) onset remains unknown. Our aim was to examine the association between IFNβ exposure and SPMS onset in MSers with relapsing-remitting MS (RRMS).

METHODS: A retrospective cohort study using British Columbia (Canada) population-based clinical and health administrative data (1985-2008) was conducted. RRMSers treated with IFNβ (n = 794) were compared with untreated contemporary (n = 933) and historical (n = 837) controls. Cohort entry was the first clinic visit during which MSers became eligible for IFNβ treatment (baseline). The outcome was time from baseline to SPMS onset. Cox regression models with IFNβ as a time-dependent exposure were adjusted for sex, and baseline age, disease duration, disability, *socioeconomic status and *comorbidities (*available for the contemporary cohorts only). Additional analyses included propensity score adjustment.

RESULTS: The median follow-up for the IFNβ-treated, untreated contemporary and historical controls were 5.7, 3.7 and 7.3 years, and the proportions of MSers reaching SPMS were 9.2%, 11.8% and 32.9%, respectively. After adjustment for confounders, IFNβ exposure was not associated with the risk of reaching SPMS when either the contemporary or the historical untreated cohorts were considered (hazard ratio 1.07; 95% confidence interval 0.93-1.48, and hazard ratio 1.04; 95% confidence interval 0.74-1.46, respectively). Further adjustments and the propensity score yielded results consistent with the main analysis.

CONCLUSIONS: Amongst MSers with RRMS, use of IFNβ was not associated with a delayed onset of SPMS.

CoI: multiple

17 comments:

  1. This demonstrates the fact that, despite all the apparent advances in MS research, the big questions remain unanswered - what causes MS, what mechanisms drive it, does it start as an inflammatory disease leading to neurodegeneration or a neurodegenerative disease which triggers an inflammatory response. You have suggested that neurodegeneration make start early in the disease. It's a pity that all the brains who turn up to the AAN conference can't come up with answers to some of these fundamental questions.

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    1. No....this demonstrates that twenty years ago when beta interferon was about that people used it and it is not that effective, we know it is not that effective. The question would be will this hold true in the age of more high active treatments.Likewise we know that inflammation causes neurodegeneration and we know that you need inflammation to clear he influences of neurodegeneration and have ideas of what mechanisms drive can drive the neurodegeneration.

      The brains aren't at ANN....the scientists are all in the lab:-)

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  2. If inflammation is the driving force in degeneration (? Primary and secondary progression) then RRMS, being clearly the most inflammatory form of MS would carry the greatest risk of serious progression. However this is not the case. Primary progressive MS, the least inflammatory variant is both the most degenerative and the least inflammatory form of the disease. 'The big questions remain unanswered'.

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    1. There are different types of inflammation. In the animals it is clear there is the lymphocyte inflammation and there is the glial inflammation the lymphocyte inflammation causes nerve loss with the relapses and the glial inflammation causes the slow nerve loss in progression. Alot of relapses early in MS is a risk factor for developing secondary progression. In some animal strains the clinical progression starts after one attack in others four attacks it depends on the individual. The lymphocyte inflammation is what is picked up on MRI and so this is one of reasons RRMS is more active than PPMS and remember on the whole, PPMS starts ten years later than RRMS and so SPMS and PPMS start around the same age. The site of the lesions is also another important factor

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    2. I got PPMS at age 27.Go figure, MouseDoc.

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    3. There will also be those who develop PPMS a lot later like the late Colin Pillinger. Also as MD says it's where the damage is, if it isn't in an area which is clinically significant, you won't notice, if it is, you will.

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  3. I think MS is understood by many at the forefront of research. Unfortunately, those closely tied to pharma are going to push immune suppressive therapies instead of focusing on stopping the disease in all forms:

    http://www.ncbi.nlm.nih.gov/pubmed/15102491

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    1. I'm not tied to pharma at all, but I can see the logic that you need to put out the flames in a forest fire before throwing more wood in. It's not one therapy but a combination of stopping inflammation, protecting the nerves and hopefully regenerating lost myelin. I think the current effective DMTs provide the immune suppressive side very well- although they could be safer with less side effects- and pharma must be looking into neuroprotection and regeneration as the next big cash cow

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  4. Essentially the same group of authors appear to be analyzing the same data set as in the famous JAMA paper: http://jama.jamanetwork.com/article.aspx?articleid=1217239 (See Figure 1 in both papers.) They're analyzing risk of secondary progression rather than risk of achieving EDSS 6, but it doesn't seem surprising that the results would look similar. At the very least, this is not an independent data point for assessing the efficacy of interferon-beta, and it inherits the methodological problems of its predecessor (not that the JAMA paper wasn't interesting).

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  5. Not long enough for this answer but the long term cambridge data there were 2 to 4 spms converters and dr C said to me that these were the people who did not do well and needed more courses of antibody.

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  6. Question was how long has lemtrada been going and what impact has it on spms

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  7. I have seen it when talking to other MSers who used interferon beta for a long time but have not had the progression of the disease braking. Would be IN them even more aggressive? I do not know, just know that if I were a neurologist and observe that my patient is not responding well to treatment with interferon, trocaraia medication immediately ... But it's not what I see out there, I've heard of many neurologists the thought "ah but having 2, 3 outbreaks a year is within the effective margin "... I see neurologists who think" factoids "to the comments about the vitamin D3 low or contagion by Epstein Barr in MSers ...

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  8. And Docs is there similar comparative study evaluating patients using glatiramer acetate?

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  9. I would like to know this as well. I started taking 40mg GA 4 months ago. I'm having a really tough time with injection site reactions..... Hope I'm not wasting my time...and skin.

    I really wish there was a better way to get an accurate prognosis at presentation. It sure would help make early treatment decisions easier (aggressive v. 1st line therapies). My neurologist says MS is so variable and dances around the prognosis question.I guess time will tell.

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    1. My old neuro used to say this to me as well ("MS is so variable"). How variable actually is it in the long term? Very few stay below edss 3.5 without being on aggressive treatment, if you look at 10-15 years out. So unless you accept a 10 year decline, why would anyone bother with the first lines? I don't get it.

      I know some have benign MS, but long term what's the odds of that over 20 years? Pretty slim I reckon. 1 in 10? It's like betting the use of your legs on the grand national at those odds?!

      I just don't see the point of them.

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  10. Something tells me this group of neuros in BC, Canada are not getting any Christmas cards from the pharma cos. selling IFNs:-)

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  11. Chuck em in the bin! and get on the lemtrada and md1003 there the only drugs worth a cheese roll !

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