High Dose Biotin another one bites the dust in progressive MS

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Biotin was a found by a chance occurrence. Biotin is one of those drugs you can get your hands on and you can eat 30 tablets a day to get the high dose in the trials. Some of you will be munching on these. But just as many of you will be ordering lipoic acid based on a drug selection study, there is no replacement for a clinical trial at present. This nutriceutical come pharmaceutical has been tested in progressive MS and it seems to have failed.

You can read the full story and trial and get the paper for free by using this link. https://authors.elsevier.com/a/1c5535FFzKo7Hl

Safety and efficacy of MD1003 (high-dose biotin) in patients
with progressive multiple sclerosis (SPI2): a randomised,
double-blind, placebo-controlled, phase 3 trial

Bruce A C Cree, Gary Cutter, Jerry S Wolinsky, Mark S Freedman, Giancarlo Comi, Gavin Giovannoni, Hans-Peter Hartung, Douglas Arnold,
Jens Kuhle, Valerie Block, Frederick E Munschauer, Frédéric Sedel, Fred D Lublin, and the SPI2 investigative teams*
Lancet Neurology:https://doi.org/10.1016/S1474-4422(20)30347-1

Background There is an unmet need to develop therapeutic interventions directed at the neurodegeneration that underlies progression in multiple sclerosis. High-dose, pharmaceutical-grade biotin (MD1003) might enhance neuronal and oligodendrocyte energetics, resulting in improved cell function, repair, or survival. The MS-SPI randomised, double-blind, placebo-controlled study found that MD1003 improved disability outcomes over 12 months in patients with progressive multiple sclerosis. The SPI2 study was designed to assess the safety and efficacy of MD1003 in progressive forms of multiple sclerosis in a larger, more representative patient cohort.

Methods SPI2 was a randomised, double-blind, parallel-group, placebo-controlled trial done at 90 aca demic and community multiple sclerosis clinics across 13 countries. Patients were aged 18–65 years, had a diagnosis of primary or secondary progressive multiple sclerosis fulfilling the revised International Panel criteria and Lublin criteria, a Kurtzke pyramidal functional subscore of at least 2 (defined as minimal disability), an expanded disability status scale (EDSS) score of 3·5–6·5, a timed 25-foot walk (TW25) of less than 40 s, evidence of clinical disability progression, and no relapses in the 2 years before enrolment. Concomitant disease-modifying therapies were allowed. Patients were randomly assigned (1:1) by an independent statistician using an interactive web response system, with stratification by study site and disease history, to receive MD1003 (oral biotin 100 mg three times daily) or placebo. Participants, investigators, and assessors were masked to treatment assignment. The primary endpoint was a composite of the proportion of participants with confirmed improvement in EDSS or TW25 at month 12, confirmed at month 15, versus baseline. The primary endpoint was assessed in the intention-to-treat analysis set, after all participants completed the month 15 visit. Safety analyses included all participants who received at least one dose of MD1003.

This trial is registered with ClinicalTrials.gov (NCT02936037) and the EudraCT database (2016-000700-29).Findings From Feb 22, 2017, to June 8, 2018, 642 participants were randomly assigned MD1003 (n=326) or placebo (n=316). The double-blind, placebo-controlled phase of the study ended when the primary endpoint for the last-entered participant was assessed on Nov 15, 2019. The mean time in the placebo-controlled phase was 20·1 months (SD 5·3; range 15–27). For the primary outcome, 39 (12%) of 326 patients in the MD1003 group compared with 29 (9%) of 316 in the placebo group improved at month 12, with confirmation at month 15 (odds ratio 1·35 [95% CI 0·81–2·26]). Treatment-emergent adverse events occurred in 277 (84%) of 331 participants in the MD1003 group and in 264 (85%) of 311 in the placebo group. 87 (26%) of 331 participants in the MD1003 group and 82 (26%) of 311 participants in the placebo group had at least one serious treatment-emergent adverse event. One (<1%) person died in the MD1003 group and there were no deaths in the placebo group. Despite use of mitigation strategies, MD1003 led to inaccurate laboratory results for tests using biotinylated antibodies.

Interpretation This study showed that MD1003 did not significantly improve disability or walking speed in patients with progressive multiple sclerosis and thus, in addition to the potential of MD1003 for deleterious health consequences from interference of laboratory tests, MD1003 cannot be recommended for treatment of progressive multiple sclerosis

This shows why it is unwise to expose yourself to potential side effects with unproven agents. As ever trial design is the key. Again the main output was EDSS and walking and sadly we know that this is a very hard task to show any positive effect on. There was no mention of other outcomes. However this was not done as an add-on and so it is not optimizing the chance of success.

Know some of you hate me for this, but it is not new and I have said it before, but when I first saw this idea being presented it struck me that thereported changes were virtually instant. This is not what you think of an disease modifying treatment for progression but perhaps an symptom control or repair agent. Trials to these effects are very different. However you want the big prize of a treatment for the progression, you have to risk of a failed trial.

COI Multiple ProfG is an author

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19 comments

  • What is high dose biotin, like the actual amount?
    I take 5000mcg after reading others on DMTs saying it helped with the side effect of hair loss. Ocrevus has made me shed my hair like a dog (at least I assume it’s this, didn’t have it before..). I was starting to bald a bit on the sides a few months after the first 2 doses. I am not normally one take supplements but I thought f it and gave it a go because I’d quite like to keep my hair.
    Not sure if the hair loss would have calmed down by itself, or if it’s the biotin, but after taking it for a few weeks less hair is falling out. Been taking for a few months now. Would be interested if there’s any evidence for it working for that.

  • High dose Biotin did seem to improve my walking, almost instantly…at first. Even people who hadn’t seen me in weeks commented upon it. And then I developed terrible heart arrhythmia, which the Cardiologist said wasn’t dangerous, but any attempt at exercise made it worse. It also gave me acne, which I hadn’t suffered from even as a teen and very greasy skin and hair. Within a few weeks the positive effects on my mobility seemed to fade, but the urging of well-meaning cheerleaders and family members to continue Biotin, as it was the only thing to ever seem to have any effect on my rapidly progressing MS, didn’t.

  • I am exactly the same as Hannah above – I take biotin because my hair was shedding after ocrevus (?the stress of the relapse or ?a direct ocrevus effect but either way I didn’t like it!)

  • Oh dear, that’s a shame. I am confident that something, somewhere, sometime and possibly unexpected will crop up to help us poor souls

  • Sorry to repeat myself but you’ve still not commented on the elephant in the room here:

    “..About 12% of patients in the MD1003 group and 9% of in the placebo group improved in either EDSS or TW25 at month 12, with confirmation at month 15 (odds ratio [OR] 1.35; 95% CI, 0.81 – 2.26; P = .31)..”

    How does one have nearly 10% of the progressive study population on placebo spontaneously improve? Has this level of placebo effect ever been experienced before on a similar group? If so, I’d certainly like to have some of that placebo as well…

    Moreover, you haven’t commented either on the apparent nearly 1:7 possibility of sustained EDSS improvement with concentrated Biotin. Where else can progressive patients go looking nowadays to find such a demonstrated effect?

    • 12% verses 9% = P=0.31 = No difference = Trial fail.
      Has people improved before…Trials are littered with improvements and placebo effects.

      ProfG may want to comment but not me, but if a subgroup improve they have to define this and do another trial…there have been thousands of people on this medication. I have looked on the website and it says “All development have been stopped”. Therefore that sounds like the end of it. As a recipient of such type of news it is brutal but that is business.

      • I am trying to “word it” in an understandable way for my adamant friends on a Biotin blog: 642 people were in the study. 68 improved. Of these, nearly half did not receive the treatment. So, do you really want to maxi-dose yourself with Biotin, the treatment, if doing nothing works just about the same?

        I’m not that interested in changing adamant minds, although the phenomenon of stubbornness is interesting (Psychologist by training), [particularly after this U.S. election cycle]. I’m more interested in the newly diagnosed or newly motivated, to carefully examine what they read and make good choices. It is so hard to argue with “It works for me so don’t tell me what to do. Only I know what is best for me, you don’t”. And then they tell others how wonderful Biotin is, saying it “works for some”, with no definition of what “works” means.

        [MSr since at least 1988] (Thanks MD, for all your info:-).

        • It works for me but taking nothing works for me too, this is why you do controlled trials…there is a graveyard of agents failed due to placebo effects but the problem for Biotin is was only ever a subsets of people claiming benefit

  • Biotin was nothing but a placebo in my opinion. And these anecdotes of improvement in bladder function were probably due to something quite undesirable. I had issues with concentrated urine when I tried biotin – at only a fraction of the trial doses. Yes I needed to go to the toilet less often, but that wasn’t healthier. I’m not going to town on lipoic acid either, as even fairly low doses – regardless of when, how I take it – give me heartburn from hell.

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