Thursday, 14 January 2016

BartsMS Off-label Cladribine use Information Sheet

For those Health Care professionals and People with MS who may be interested. 

We have updated our Information concerning off-label cladribine use at BartsHealth.


Barts ms clinical guidance for cladribine from BartsMSBlog

There is also information concerning the subcutaneous Administration of Cladribine



Furthermore people enrolling must sign a consent form and be very clear why they are willing to try cladribine. 



We want the best choices for people in our care. 

These may well be the current MS Pharma produced DMT.

However, at BartsMS we are at least willing to try some thing different when these avenues may not be available. 

The documents above show we are prepared to consider Cladribine as an off-label treatment (as we have done it on a similar individual basis, for example, with Rituximab) in situations where (i) eligibility for licensed DMTs cannot be established, or (ii) pwMS, together with the BartsMS team, make an informed decision in favour of off-label treatment rather than a licensed DMT. 

16 comments:

  1. If Cladribine is really cheap and as good as you keep saying, do you think there are neurologists that would consider prescribing it on a private basis? At the moment, the only NHS options first line (ignoring the lower efficacy CRABs as we all know time is brain) are Tecfidera and Alemtuzumab. And Alemtuzumab causes thyroid problems in approx 50% of cases. I know there are large ethical considerations ignoring the licensed available drugs that fund new research, but it's not an ideal position at the moment. I vaguely remember Prof G posting on privately prescribing a drug a while back. I don't know I'd be up for it, I was just interested in the ethics of the possibility.

    I am taking Tecfidera at the moment but hanging on to hope that Ocrelizumab might become available first line or that Tec is effective or at the worst, I have very (very) mild indications of activity enough to bump me into second line therapies.

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  2. The documents above show we are prepared to consider Cladribine as an off-label treatment (as we have done it on a similar individual basis, for example, with Rituximab) in situations where (i) eligibility for licensed DMTs cannot be established, or (ii) pwMS, together with the BartsMS team, make an informed decision in favour of off-label treatment rather than a licensed DMT. I don't know whether there are colleagues doing this on a private basis, however don't see a reason why, as a matter of principle, that should not be an option.

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  3. Since the MOA of Clabridine is to suppress your immune system, what is your view of the the risk of PML? As PML did not show up in the Tysabri 2 year trial nor the BG12 2 year trial and occurances have oy become evident with these drugs in thee post marketing phase it seems likely it will show up in Clabridine as well.

    However since this will be used off label the impact of PML from this drug to the MS community will be out of sight of regulators. What is your response?

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    1. Neither am I aware of a single case of PML reported in a pwMS treated with Cladribine. Mind you that be front page material given that even a – non-fatal – case of an 81 year old patient who developed PML after being treated *for leukaemia* was highlighted at the meeting of the American Academy in 2011 (http://hairy-cell-leukemia.blogspot.co.uk/2012/04/aan-case-report-links-cladribine-to-pml.html). Bearing in mind the fact people with leukaemia are at an increased risk of opportunistic infections, such as PML, any case of PML in a pwMS on Cladribine would in the UK be flagged through the Yellow Card system (https://yellowcard.mhra.gov.uk/). This system helps the MHRA keeping track of the safety of all licensed drugs (remember, Cladribine is a licensed drug, it is only off-label for conditions other than hairy cell leukaemia!).

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    2. The immunosuppression with induction treatments, such as Cladribine or Alemtuzumab, differs from say a Fumarate preparation in that lymphocyte populaitons will recover following induction whilst it is people with chronic lymphopenia - as it can happen with Fumarates - that are at risk of PML. Natalizumab is a special case, discussed many times over.

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    3. Maybe DrK can clarify further and comment about the MS register as I believe people will also in this system too. If you are based in the UK please register.

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    4. Indeed, we ask all pwMS to sign up to the MS Register, and particularly so those receiving induction treatments.

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    5. I thought Dr. G posted that it was illegal in the UK to prescribe medication off label if there is an existing approved therapy.

      If this is the case would you not have to have tried and failed all approved therapies before you could legally go on Clabridine?

      If not this seems like it would violate the unwritten "grand bargain" that pharma has with the government.

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    6. Re: "I thought Dr. G posted that it was illegal in the UK to prescribe medication off label if there is an existing approved therapy."

      At a systems level yes; i.e. the NHS couldn't mandate this. However, we are mainly using cladribine in place of mitoxantrone, to cover patients who are not eligible for treatment under current NHS England prescribing guidelines. Please note we used mitoxantrone off-label as well.

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    7. If we're not open to pwMS sometimes making choices that are oblique to the grand bargain table we violate our doctor-patient relationship, which is a notch higher on my scale.

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    8. Please review what the minster wrote when they blocked the repurposing bill. His letter was posted on the blog.

      It was very clear in his mind that a doctor could prescribe off label.

      I am surprised that there are decenting voices when more choice could be on offer. Surely anyone with MS would not want less choice.

      I

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    9. Many years ago all you could get white cotton Y fronts isnt it better that you have colour different shapes and forms and yes there are a few nightmares as who got the comedy underware for christmas however more choice is better as i wouldnt be caught dead in white Y fronts..... same with ms drugs :-)

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    10. Please review what the minster wrote when they blocked the repurposing bill. His letter was posted on the blog.

      It was very clear in his mind that a doctor could prescribe off label.

      I am surprised that there are decenting voices when more choice could be on offer. Surely anyone with MS would not want less choice.

      I

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  4. Check my math(s):

    0.14 mg per kg
    Therefore (am 90 kg)
    90 * 0.14 = 12.6mg
    1ml -> of drug
    12.6/2 -> 6.3 ml
    Therefore
    1x5ml and 1x 1.3ml

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    Replies
    1. Your maths are correct Aidan, however they are based on the assumption that 0.14mg/kg is the *total dose* we wish to achieve, which is not the case. What we are aiming for is the bioavailable equivalent of Cladribine that was used in the lower dose arm (3.5mg/kg) over 2 years during the CLARITY trial (CLARITY duration was slightly shorter, 96 weeks). In CLARITY a 70kg individual would have received 3.5*70 = 245mg Cladribine over 96 weeks. Given bioavailability of Movectro is ~42%, an equivalent subcutaneous dose would be 103mg. This figure closely matches our dosing scheme, however we have built in the added mechanism of *adapting the dose to lymphocyte count* in order to avoid, as best as we can, any severe lymphopenia. We discussed giving people >90kg an additional injection (4 instead of 3 injections during week 1 of the first cycle), so you would be right on the edge!

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    2. 90kg was my pre holiday season weight, 10lbs over now - chomping on a salad for lunch.

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