Friday, 5 December 2014

Pegylated interferon-beta 2-year follow-up

Is there a need for pegylated interferon? #MSBlog #MSResearch

"The study below shows that the effect of long-acting beta-interferon extends into year 2. Are you suprised? I am not!"

"I can't get my name around the tradename of this product; Plegridy. I assume the Pleg is a play on Peg from pegylated and ridy on me-too; I a new version of Avonex. I prefer to refer to Plegridy as long-acting Avonex. The problem is that Plegridy is given subcutaneously and Avonex intramuscularly. The switch in route of administration for me is a problem; one of the main selling points of Avonex is the fact that it is given intramuscularly and avoids the skin reactions, which are a problem with Plegridy and the other subcutaneous interferons."

"What is pegylated? This is when medicinal chemists, or molecular biologists, add a molecule, polyethylene glycol or PEG, onto proteins to extend their circulating life span in the body. I am personally not convinced that we need a pegylated form of interferon-beta in MS. In general interferons don't have much of an impact on end-organ damage; i.e. brain volume loss or brain atrophy. The possible exception is Avonex, that is only given once a week, and has been shown to reduce brain volume loss. Why is Avonex an outlier? It may relate to the fact that it stimulates it receptor intermittently, whereas the more frequently administered formulations and pegylated-interferon stimulate the receptor continuously. This is why I need to see brain atrophy data on Plegridy before recommending Plegridy as a routine choice to my patients. Has pegylation killed off one of the differentiators between the interferons?"

"When you see the a patient who is eligible for a DMT the discussion has now changed. The initial focus is on the treatment strategy; maintenance-escalation vs. induction. If the choose the maintenance-escalation  strategy you ask them if they are interested in an injectable or an oral therapy; most say an oral. This is before we get to discuss the attributes of the different classes of injectables; i.e. interferons vs. GA. If they choose the interferons we then starting discussing subcutaneous vs. intramuscular (no skin reactions vs. skin reactions), neutralising antibody (NAB) rates, flu-like side effect persistence (greatest with Avonex), etc. Based on this I am not sure that there is a place for a pegylated interferon. What do you think? Very few MSers will follow the decision-tree down to Plegridy; may be having the option is better than not having the option."


Epub: Kieseier et al. Peginterferon beta-1a in multiple sclerosis: 2-year results from ADVANCE. Mult Scler. 2014 Nov 28. pii: 1352458514557986.

OBJECTIVE: To evaluate the efficacy and safety of subcutaneous peginterferon beta-1a over 2 years in patients with relapsing-remitting multiple sclerosis in the ADVANCE study.

METHODS: MSers were randomized to placebo or 125 µg peginterferon beta-1a every 2 or 4 weeks. For Year 2 (Y2), MSers originally randomized to placebo were re-randomized to peginterferon beta-1a every 2 weeks or every 4 weeks. MSers randomized to peginterferon beta-1a in Year 1 (Y1) remained on the same dosing regimen in Y2.

RESULTS: Compared with Y1, annualized relapse rate (ARR) was further reduced in Y2 with every 2 week dosing (Y1: 0.230 [95% CI 0.183-0.291], Y2: 0.178 [0.136-0.233]) and maintained with every 4 week dosing (Y1: 0.286 [0.231-0.355], Y2: 0.291 [0.231-0.368]). MSers starting peginterferon beta-1a from Y1 displayed improved efficacy versus patients initially assigned placebo, with reductions in ARR (every 2 weeks: 37%, p<0.0001; every 4 weeks: 17%, p=0.0906), risk of relapse (every 2 weeks: 39%, p<0.0001; every 4 weeks: 19%, p=0.0465), 12-week disability progression (every 2 weeks: 33%, p=0.0257; every 4 weeks: 25%, p=0.0960), and 24-week disability progression (every 2 weeks: 41%, p=0.0137; every 4 weeks: 9%, p=0.6243). Over 2 years, greater reductions were observed with every 2 week versus every 4 week dosing for all endpoints and peginterferon beta-1a was well tolerated.

CONCLUSIONS: Peginterferon beta-1a efficacy is maintained beyond 1 year, with greater effects observed with every 2 week versus every 4 week dosing, and a similar safety profile to Y1.

CoI: multiple

6 comments:

  1. It is interesting how different MS centers look at the efficacy of drugs.

    For example, here is an overview of the Rocky Mountain MS Center's evaluation of DMD's:

    http://mscenter.org/dev/images/stories/Vollmer-_Disease_Modifying_Therapies_for_Multiple_Sclerosis_4_up.pdf

    As you can see on page 6, Avonex is rated as having the worst ranking in terms of atrophy (the same as all interferons). You on the other hand rank Avonex to be better than the other interferons. Why the descrepancy?

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  2. Here we go again - more data on Relapse Rates - all highly pointless if you are SPMS or PPMS with no meds approved for these. I feel more and more like a leper every day with this never-ending focus on relapses. And I don't want to hear any comments about reducing relapse rates means people taking longer to get worse - if you never had relapses in the first place then it's all irrelevant anyway.

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  3. Perhaps Plagiaferon would have been a better name? ;-)

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  4. I am surprised that researchers did not develop pegylated interferon at the outset in the 90's. Ribavirin, a pegylated alpha2 IFN developed for Hep C, also has an increased bio-availabiltiy due to PEG. It seems that the beta inteferons should have been pegylated from the get go.

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  5. surprised that researchers did not develop pegylated interferon at the outset in the 90's. Ribavirin, interfon bloc

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