Wednesday, 11 May 2016

Plegridy 5 Year follow-up at AAN

ADVANCE Phase 3 Extension Study (ATTAIN): Peginterferon Beta-1a 125 mcg Every 2 Weeks Demonstrated Sustained Efficacy in RMS Patients Treated up to 5 Years 

Authors: Damian Fiore; Serena Hung, MD; Weihua Tang; Yue Cui; Xiaojun You, PhD; Shulian Shang; Thomas Scott, MD Objective: To investigate the long-term clinical efficacy of peginterferon beta-1a in patients with relapsing multiple sclerosis (RMS). 

Background: Peginterferon beta-1a every 2 weeks has been approved in the US for the treatment of RMS (and is approved in >20 countries), based on Year 1 results from the pivotal Phase 3 2-year ADVANCE study. The secondary outcomes for the 2-year ATTAIN study, the extension of ADVANCE, evaluate long-term efficacy of peginterferon beta-1a. 
Design/Methods: RMS patients who had completed ADVANCE were eligible for enrollment in ATTAIN. Patients were maintained on the peginterferon beta-1a dosing regimen they were assigned in ADVANCE Year 2. The study was considered complete when the last patient completed Week 96 of ATTAIN. Annualized relapse rates (ARRs) were evaluated in all patients who had received peginterferon beta-1a beginning in Year 1 of ADVANCE, for all years that they had received therapy (up to 6 years). In the absence of a long-term placebo comparator, peginterferon beta-1a every 4 weeks was used as a control for the approved peginterferon beta-1a every 2 weeks dosing regimen. 
Results: The ITT population for Years 0 to 6 was n=376 for patients receiving peginterferon beta-1a every 2 weeks, and n=354 every 4 weeks (ATTAIN ITT population). Over 6 years, adjusted ARR was significantly improved in the peginterferon beta-1a every 2 weeks group (0.188) compared with the every 4 weeks group (0.263; rate ratio 0.714; 95% CI 0.563-0.904; P=0.0052). Year-over-year adjusted ARRs were generally reduced in the every 2 weeks group (Years 0-1: 0.241, n=376; Years 1-2: 0.179, n=376; Years 2-3: 0.203, n=376; Years 3-4: 0.129, n=338). 
Conclusions: At the approved every 2 weeks dosing schedule, peginterferon beta-1a displays significantly improved ARR over 6 years compared with every 4 weeks dosing. Additionally, year-over-year results for peginterferon beta-1a every 2 weeks demonstrate sustained efficacy with long-term treatment. 

If the answer is CRAB! What's the question?

But as beta interferons come out of patent, phamra have repurposed beta interferon by adding anti-freeze (Polyethylen glycol = PEG). This gives it a longer time in circulation. So this study shows it works over 5years of use but the results are about twice as bad as generic cladribine,

40 comments:

  1. Mate, I'm not gonna comment on this particular post because it's boring. I do, however, feel most humbled with the welcome back comments one has received. You're all good kids, and Daddy Dre missed you all, even those of you who give me a hard time and defame my good character.

    I have been away. I was in Detroit, found America boring as usual, jetted off to Dubai for a week, it ended up being four months, got hot, flew to London, am staying put for the summer because Britain does it like nobody does.

    This is a great country but it can be even greater. The UK keeps it real. Its people are real, not fantasists. There is impeccable decency here as evidenced by our NHS: the greatest statement of betterment since time memorial.

    This blog needs to stop boosting Big Pharma's profile and start giving it large about how splendid the NHS is. Let's get the word out there. Defend it, friends. Defend the BBC. Defend our socialist and equitable way of life. You know it makes˚ sense.

    I love Britain. I love the British. Let's never choose to be like the Americans and eat burgers till we explode. Let's not be like the Chinese who worship money. Let's stay compassionate. Love one another.

    Peace.

    ReplyDelete
    Replies
    1. Dear Dre,
      A quick question to clarify things for your fans, do you or a family member/friend have MS? I think it'll help put things in context for our visitors.
      Thanks
      MD2

      Delete
    2. I'm just normal British kid like you all, Mini-Mouse. I put my pants on one leg at a time, just like you or Don Giovannoni.

      What is MS? What is this thing called life? It's just language and words. People are too nosy nowadays.

      My mystery is me. My privacy is sacred. My greatness speaks for itself. I think I my be a god, though not the God ... or I might be on second thoughts ...

      Delete
    3. I'll take that as a no then and we can treat your future comments accordingly.
      Thanks

      Delete
    4. Take me as I am, not as you want me to be, Mini-Mouse ... Come as you are, as you were, as I want you to be, choice is yours, don't be late ...

      Delete
    5. This is a joke?! That's what I understood it?! The guy up there has not MS, and is commenting as if he had the disease or have it and don't want to come out?!

      Interferon is a big crap ... upper side effects, be more superior than the actual efficacy of the drug.
      If I make a "research" with anyone who uses any of the forms of Interferon Beta certainly more than 80% have more adverse side effects than benefits with this drug...

      Delete
    6. Dre
      That joke isn't funny anymore..................

      Delete
    7. Dre...why are you quoting Nirvana lyrics? Do all rappers just recycle old lyrics?

      Delete
    8. Dre Dre Dre,

      Wrapping the rap today. America and burgers you say? But big food companies start where you stay! While I love Britain all day, BP done killed the Gulf bay. They may keep it real as you say, but business is business no matter where these days.

      Delete
    9. There was a young man from Japan
      Who wrote verses that never would scan
      When told it was so he replied, yes I know
      But I always try and fit as many words into the last line as I possibly can
      ;-)

      Delete
    10. Who is this Cinara person? What is a Ms Unites? Where has the old crew gone? Where is my mate Lexi? What happened to VV? Man, the old possee was legendary. We were like a comedy steno pool from the Hollywood Golden Age. We had a laugh and respected one another. Even Don Giovannoni used to kick back with us.

      The blog has gone all serious. No-one's having a laugh any more.

      Fret thee not, brothers. I'm here to lower the tone and get you MSers looking at the bright side of life again. Laughter truly is the best medicine. You'll be discarding those expensive and useless DMTs in favour of a chuckle in no time. Just stick with me, brave.

      (PS - America owns BP now. They kept the brand because 'Britain' invokes greater class and regency than, say, U.S.P.

      Delete
    11. I write poetry at times and other thingies. Ever see my MS Christmas Song?

      Dashing through the snow with MS on our sleigh over hills we go who knows what on its way?

      No bells our tale shall ring, try keep our spirits bright, oh what fun it is to sing our MS song tonight.

      Tingle bells, tingle bells, tingle all the day... Of what fun it is to ride with MS in our sleigh.

      Delete
    12. Then there is my parody of Creedence "Old cotton fields back home"

      When I was a little bitty baby
      My mama would sock me with a ladle,
      In them mold rotten fields back home;

      It was down in Louisiana,
      Just about a mile from Texarkana,
      In them mold rotten fields back home.

      Oh, when them cotton bolls get rotten
      Allergies would bring on fever and snottin',
      In them mold rotten fields back home.

      It was down in Louisiana,
      Just about a mile from Texarkana,
      In them mold rotten fields back home.

      Delete
    13. Hi Dre,
      Your fan club seems to have gone quiet. I wonder why? Could it be they now consider you an imposter? Still we can all do with a laugh and your posts manage that (intended or not).

      Delete
    14. Cinara is the cheerleader for Team G. MS Unites is a new entity and has just recently become a very active poster.

      But none compare to Dre.

      Delete
    15. They don't compare to Dre for reasons that I'm sure you and others have worked out. Which puts Dre's relentless nihilism in context.

      Delete
    16. Dre has got a funny way with words but what he advocates will ruin lives. He uses his charm to encourage people to stop treating their MS. It's really unpleasant.

      Don't pretend your body can fully repair every relapse. Mine hasn't. If your DMD stops just one relapse, maybe that relapse would have been the one that left you permanently incontinent, semi-blind, or dependent on a walking stick.

      Let's say you have ten years before you hit progression, surely you want to make those ten years good ones, make them as free from MS as you possibly can, hold the monster at bay and cherish your health while it lasts. Why let MS ravage you without fighting back?

      PPMSers are desperately crying out for drugs that can slow their disease, anything that can buy them some time. Why are we still wasting ours?

      Delete
    17. I do love reading Dre's comments, though, even when I disagree with him. He's very entertaining and wonderfully playful.

      Let's keep him.

      Delete
    18. Dude, I'm a person, a woman with MS, seeking information about the disease and that has nothing more than that.

      Yes, laugh is the best medicine, but there are issues that not funny at all, unless you have some sociopathy or only be possessed of "black humor."

      To apologize to no medication about MS is the same as saying "guy do what I say, but don't do what I do." Wow sure, you really don't, you probably don't use any DMT since you don't have MS, you don't know what it's to have the disease and deal with what affects the other form of "playfulness", you don't have to live among the dilemma "bad with them, much worse without them"...

      And if I'm "G Team fan", if you consider me this doesn't bother me.
      I come here every day because here there is real information to people with MS, professional health and research, and moreover disseminated information in an accessible way to all public, and fosters debate.

      If you know another space so or on the Internet or associations let me know because I have tried and found...

      Delete
    19. Cinara, believe it or not, Dre is actually a complex character. He is very anti-DMTs, however. He seems to label decent medicines of MS as rubbish.

      I do like his politics, however. He stuck up for disabled people when certain commentators were being throughly condescending to them last year. As a disabled MSer I appreciated that because he really shamed them and made their comments look stupid. He also made powerful and intelligent comments about assisted suicide once.

      You'll get used to him, hopefully. He's good to have on your side.

      Delete
    20. @Kev, really you think you can label someone as a "complex character" simply by reading some slick rhetoric on a blog. For one, he said in was visiting Detroit, I have reservations about him or her already, who does that unless it was business? There is nothing wrong with stirring up the pot and sparking a conversation but come on. See from my post you probably think I'm an a**, you never know. Now back to our regularly scheduled program...ccsvi, ebv, stem cell debates, remyelination, diet, vit d,being born under a bad sign etc.;-).

      Delete
    21. DETROIT.. MAYBE HE IS JUST A (used) CAR SALEMAN. MAYBE HE HAS SEEN THE LIGHT AND SINGING A NICE BIT OF MOTOWN AS OPPOSED TO RAP

      Delete
    22. Oh yeah Motown Barry Gordie and Hitsville, now that was music.

      Delete
    23. Detroits actually a shadow of its former self. Shame as historically its an amazing place. The once great "Ford theater" lay in ruin. Many very historical buildings that were initially built for US Civil War amputee's been destroyed as no money to do upkeep.

      Last I knew General Motors with Hydrogen fuel cells partnered up with Honda and they'll be made in Japan. Our city (Rochester) was up for this years back. There is everything needed to create them within a 100 mile radius. Nope. Phhht.

      Now we are to be one of the hubs for photonics. Photonics are electronics essentially that use light .vs. traditional electrical current. I guess both speed in things such as microprocessors and size of them can be greatly enhanced. Makes sense given different wave lengths of light.

      As Spock would say, "Fascinating"

      Delete
    24. My apologies to Mr. Berry Gordy on butchering his name.

      Delete
  2. I'm intrigued at the sudden 10% attrition rate seen in years 3-4 (376 to 338 patients). Could this be related to lack of efficacy or NAbs?

    Do you know if the ARR in years 3-4 was also calculated as ITT analysis?

    ReplyDelete
  3. When I was a student in Manchester, I recall one Sunday night getting the bus to the students union to start my shift behind the bar. The champagne socialists from the student socialist worker collective were also on the bus heading to the bar to start drinking. Their topic of conversation was how good the skiing was in Aspen that year.

    ReplyDelete
    Replies
    1. We're all Prosecco socialists round here, Aidan ;-)

      Delete
  4. Pegylated interferon is just pharma reacting to patent expiration. Modify IFN-beta and try to squeeze out more profit from a therapy that has seen its time. I think everyone can read between the lines. If the MS mantra is "hit hard hit early" then IFN is hardly a player.

    ReplyDelete
  5. I know quite a few people still using Avonex and Rebif that have done well for years on end. Then there are others who just sorta "Snapped On". For example, my fiance' has two neighbors both with MS. Lots of MS where I live. She took Interferon for years and years. She was a school bus driver. No disease progression at all. Then few years back she retired and BAM, she starts having exacerbations. She went on Copaxone, didnt help. She tried Gilenya and was taken off that. Now she's on Aubagio and its working really well for her.

    ReplyDelete
  6. Glatiramer, interferons means: waste of valuable time. Please forgot these drugs which do not have any effect on BVL, which correlates best with further progression! So this is the time of fingolimod, natalizumab, alemtuzumab, ocrelizumab, daclizumab, or the offlabel cladribine!

    ReplyDelete
  7. In respect to off label cladribine I wonder if it can be taken with LDN?

    I presently am on TicFudera (Dimethyl Fumarate Unleaded). I go for an MRI soon to see if I am NEDA or NODDA (No Operational Difference in Disease Activity <--- Brilliant Yes?). Since I take LDN and I am high JC Positive my present options are limited. When asked BioPharma about Gilenya / Aubagio was told that it was ill-advised (liver & onions) .vs. Tecfidera.

    While my present Neurologist probably wouldnt do cladribine (though might) I know another who is very credentialed that probably would. He's really versatile.

    ReplyDelete
    Replies
    1. I'm not aware of any data on combination treatment Cladribine + LDN. Theoretically, I would not expect any significant interaction between these drugs.

      Delete
    2. Thanks so much for the response. Hopefully Tecfidera does its noble duty. If it doesnt though my options get scary. LDN is sort of my safety blanket. I am literally scared to go off it. I am one of those people that it's really made a significant difference from where I was to where I am.

      Delete
    3. LDN is more comfort food than safety blanket there is good evidence base for it being useful....I am amazed that the MS Societies dont try to get the good evidence to support its use as so many people with MS are usingLDN

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    4. Erratum I meant to write this is no good evidence....

      Delete

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