Saturday, 30 January 2016

ClinicSpeak: switching from an injectable to an oral DMT

The power of data; moving mountains and liberating people with MS. #ClinicSpeak #MSBlog #MSResearch

"Better the devil you know that the devil you don't. I have been telling my patients who are stable on an injectable that as they are responding to a particular class of DMT do they really want to take a chance and switch  to an oral a new class of DMT when we have no idea if they will respond to or not?"

"I have been saying that if you are currently a responder (NEDA-3) to IFNbeta or glatiramer acetate we have no idea if you will respond to DMF (dimethyl fumarate, Tecfidera) or teriflunomide (Aubagio). As these drugs have different modes of action I have no idea if response to one drug predicts response to another drug. The good news is that it appears I was wrong. The study below using real-life data from MSBase shows that pwMS stable on IFNbeta or GA have no increased relapse rate when they switch to an oral. Good news? Yes, very good news. I know a large number of patients who are simply tired of injecting themselves who will now want to make the switch. It shows you the power of data. Data can move mountains."


"Congratulations to the MSBase team for another wonderful publication. You are really making a difference to the way we practice clinical neurology. I am sure a lot of pwMS will be thankful for your efforts; particularly this study. Prof G can't sit on the fence anymore."

Epub: Spelman et al. Risk of early relapse following the switch from injectables to oral agents for multiple sclerosis. Eur J Neurol. 2016 Jan 19. doi: 10.1111/ene.12929.

BACKGROUND AND PURPOSE: Early relapse outcomes in long-term stable patients switching from interferon β/glatiramer acetate (IFNβ/GA) to oral therapy are unknown.

OBJECTIVE: The objective of this study was to compare early relapse and progression in multiple sclerosis (MS) patients switching to oral therapy following a period of stable disease on IFNβ/GA, relative to a propensity-matched comparator of patients remaining on IFNβ/GA.

METHODS: The MSBase cohort study is a global, longitudinal registry for MS. Time to first 6-month relapse in previously stable MS patients switching from platform injectables ('switchers') to oral agents were compared with propensity-matched patients remaining on IFNβ/GA ('stayers') using a Cox marginal model.

RESULTS: Three-hundred and ninety-six switchers were successfully matched to 396 stayers on a 1:1 basis. There was no difference in the proportion of patients recording at least one relapse in the first 1-6 months by treatment arm (7.3% switchers, 6.6% stayers; P = 0.675). The mean annualized relapse rate (P = 0.493) and the rate of first 6-month relapse by treatment arm (hazard ratio 1.22, 95% confidence interval 0.70, 2.11) were also comparable. There was no difference in the rate of disability progression by treatment arm (hazard ratio 1.43, 95% confidence interval 0.63, 3.26).

CONCLUSION: This is the first study to compare early relapse switch probability in the period immediately following switch to oral treatment in a population previously stable on injectable therapy. There was no evidence of disease reactivation within the first 6 months of switching to oral therapy.

CoI: multiple

25 comments:

  1. I've been NEDA-3 on IFN-beta since diagnosis 2 years ago. But since there's no reliable way of telling whether I'm NEDA-4 or NEDA-5, I'm taking the leap to Lemtrada in a couple of months. Why switch to a statistically less efficacious oral if the potential side effects of Lemtrada can be treated/managed when detected early?

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    1. You might well become an HSCT medical tourists. Go full bore or nothing at all. Right Team G?

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    2. We are not going to support tourism.

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    3. Because we are not Thomsas Cook
      https://en.wikipedia.org/wiki/Thomas_Cook
      we can't tell you were to go and where not to go

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  2. The oral drugs have as good or better efficacy than injectables. So why would a patient choose an IFN or Copaxone if they don't have greater benefit?

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  3. I'm tired of injecting, yes. But there's still something to be said for the side effect profile of my old DMT.

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    1. Good point. They really didn't compare adverse effects of the switch. Also one would expect the relapse rate and effect on disability to be more significant on the "highly effective" oral drugs instead of there being no statistically significant difference.

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    2. They could have easily tracked adverse events just as they did relapse rate and disability progression. They probably did, but I suspect this was left out of the paper as the hidden authors are "MSBase Study Group[Corporate Author]" It was obviously detrimental to the oral drugs.

      They were probably expecting the relapse rate and disability effects to be favorable to the oral drug, but it didn't turn out the way they expected.

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    3. Anon Jan 31 11:53 am: "MSBase Study Group[Corporate Author]".

      I'd like to highlight that the MS Base Study Group have essentially set up a national registry in Australia, such an endeavour requires money and are funded by grants, charities and cooperate money. Similar ventures exist in the UK, the most well known is the UK MS registry. MS researchers apply with a specific question, an example of it is this study and that alone comprises of the analysis.

      Clinical trials already do a good job of tracking adverse events with extension studies lasting +10 years, an analysis of registry findings which is biased by the number of PwMS registered is unlikely to add further to these findings.

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    4. Here are the sponsors to the MSBASE Study Grouo:

      https://www.msbase.org/cms/sponsors_and_donors.html;jsessionid=19b674obbl1siuf51ixphvi9u

      It's pretty self explanatory.

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    5. So Neuro Doc Gnanapavan,

      The trials are good at tracking adverse events, the oral drugs have significantly more severe effects since they are immunosupressant in nature, the MSBase have found that there is no significant difference in relapse rate or disability progression in theses patients.

      So what do you recommend, stay or switch?

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    6. Anon Sun, Jan 31,2016 9.30pm - this is available for everyone to view. Not to get too embroiled politically, I wish that what you deem "respectable" funding bodies would support more projects such as these, but I suspect they do not have this scale of funding to sustain the project.

      Anon Sun, Jan 31, 2016 9:40pm. My read of the study is that we're talking about time to first relapse - and this is not significant between the switchers and non-switchers; I will be wary of interpreting anything else beyond this. I definitely don't think its sufficiently powered given the low relapse rates to say much about its effect on disability!

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  4. Anon 5:47;

    I didn't mention HSCT? I'm taking about a trailed & approved induction therapy in Australia.

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  5. The well established safety profile of injectables is a huge advantage. I know of 2 fellow MSers who have been very stable on Copaxone and refuse to switch to a oral drug just because of potential unknown side effects.

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    1. The same can be said for some people have been stable not on drugs, however they are others that don't do well.

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    2. MD: To be clear, are you saying that someone who is NEDA-3 on Copaxone is taking the same risks as someone NEDA-3 on no DMTs?

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    3. No the risks of the dmt are the risks

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  6. We just had this discussion last week with a few neuro's and a former assistant state attorney general from Ohio who has MS. When adverse events crop up with injectables which does happen over time with many patients they switch. Their protocol is if a patient has low JCV risk they go Tysabri for its efficacy profile. If JCV risk is high they first tend recommend Aubagio given the liver concerns are not present in the patient.

    However, both neuros in their practices said more often than not transitions are made due to compliance with using the injectables.

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    Replies
    1. This is just the view of some neurologists and how they switch and what they switch to.

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  7. I guess if you compare the relapse rate and progression of a drug like Copaxone when it becomes active (yes it takes six months before it becomes effective) to that of the "highly effective" orals there is no difference.

    Unfortunately many people like the Team G'ers think MS is EAE and look at how quickly a drug becomes effective, so of course any immunosupressant is superior in the short term 2 year trial, but this has no bearing on the longterm outcome.

    I guess this is why immunosupressaion is the way forward for MS therapies because too many researchers are using EAE as a crutch instead of trying to understand the disease. This and the fact that 30 year old repurposed chemotherapeutic agents are a simple boondoggle for the pharmaceutical companies.

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    1. Are you suggesting the CRAB drugs are no less efficacious than the highly effective therapies in the longer term? Hardly.

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    2. "Unfortunately many people like the Team G'ers think MS is EAE..."
      Actually, we don't, we never have but I would say that our model is a pretty good correlate in comparison to the more commonly used EAE models. It isn't perfect but its the best we've got and when you see the prediction of Figolimod not affecting progression from our EAE work being repeated in humans this result seems to bear that out.
      I very much doubt that more effective immunosuppressants will have no bearing on long-term outcome, stopping relapses has to have a positive effect (still early days for the follow up data) though we will still need neuroprotectives as well to really hopefully stop progression in its tracks or at least slow it down significantly.

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    3. I never said immunosuppressants won't have an impact on the longterm course of the disease, particularly if started early I. the disease, but it seems those on injectable like Copaxone that respond have stabilized their disease. This is proven out by the 15 year long-term extension trial as well as this latest report that this post is about.

      You may deem the extension study of Copaxone as invalid as it is an observational study, but then you must take the same mindset with this latest report.

      So if you have really active disease Copaxone is not going to work for you because as stated earlier it has been observed that it takes 6 months for it to become effective.

      http://dailymed.nlm.nih.gov/dailymed/archives/image.cfm?archiveid=11323&type=img&name=copaxone-01.jpg

      So for those with active disease or the inability to tolerate injections, the Oral meds may be a better choice but it seems Copaxone has stellar safety record, shows to be effective in some MSer over the longterm and does not suppress your immune system which is why I chose it.

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    4. "...of course any immunosupressant is superior in the short term 2 year trial, but this has no bearing on the longterm outcome." This isn't what the CARE-MS 7 year extension study suggested.

      Personally I'd rather suppress *any* activity with a stronger but calculated risk. Alemtuxumab isn't a new drug. I know too many who did well on a CRAB drug for some time, before their disease took a drastic turn. They had then missed the window of opportunity for a highly effective drug to be just that, highly effective.

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