Great article and interesting that most 'subjects' are pursuing the Alemtuzumab or HSCT route. On these, what is the theory behind halting the progression to SPMS and are there any studies that have tested this over a long period? is the data for HSCT different from Alemtuzumab on this particular disease marker?
The impact on progression in more advanced MS with all DMTs including alemtuzumab and AHSCT is relatively poor, i.e. it slows down worsening and does not stop it. A lot of AHSCT centres avoid offering AHSCT in SPMS unless there is a lot of ongoing inflammatory activity. The same applies to alemtuzumab.
I'm surprised to read that you consider NICE guidelines to be legal obligations! What about the times when it says you can't prescribe? As professionals do we not retain our right to treat according to our opinion and conscience, referring on to another specialist if need be? I do not think that a NICE determination compels me to produce a prescription.
Re: "I do not think that a NICE determination compels me to produce a prescription."
I agree, but you would have to refer the patient to someone else if that patient is eligible for a NICE approved treatment and they want to be treated with it. This is about the NHS having to provide the treatment, not the individual prescriber. In fact, only MSologists working at NHS England approved MS centres can prescribe alemtuzumab and the other licensed monoclonals in England.
I thought so too, but at a meeting 2 years ago a medicolegal barrister pointed out to us that the legislation underpinning the creation of NICE put this onus on the NHS to offer NICE approved medications if patients are eligible for them. How else would NICE, i.e. the government, be able to claim they have dealt with the postcode prescribing lottery? This is why NICE is such a powerful organisation.
Another excellent case study and encouragement. I didn't know that if you met the NICE criteria a neurologist has a legal obligation to prescribe. It might have saved me transferring from a risk averse neurologist and getting stuck on Fingolimod at my new centre. But fair dos through just about to start cladribine aftet a relapse. Neurologist number 1 would not have agreed
It was my understanding that Lemtrada can not be prescribed as a first line therapy anymore, following the recent EMA recommendations. Did I get this wrong? If I got this right, what constitutes failure on other heDMTs like Tysabri? New MRI evidence of disease activity after 6 months of use? What about subjective feelings such as cognitive impairment, memory issues becoming more prominent and the like?
If you are eligible for natalizumab (Tysabri) you are eligible for alemtuzumab. You can just switch. The one caveat is if you are JCV positive and have been on natalizumab for longer than 12 months you need to be careful and make sure you don't have asymptomatic PML that can be carried over to alemtuzumab. This is why we bridge patients on fingolimod.
The following is the indication in the SmPC as you can see the second indication or RES can be 1st-line use.
4.1 Therapeutic indications
LEMTRADA is indicated as a single disease-modifying therapy in adults with highly active relapsing-remitting multiple sclerosis (RRMS) for the following patient groups:
• Patients with highly active disease despite a full and adequate course of treatment with at least one disease-modifying therapy (DMT)
OR
• Patients with rapidly evolving severe relapsing-remitting multiple sclerosis defined by 2 or more disabling relapses in one year, and with 1 or more Gadolinium enhancing lesions on brain MRI or a significant increase in T2 lesion load as compared to a previous recent MRI.
Dear Sir, you mention that AHSCT and Lemtrada are more effective at turning off smouldering MS and slowing down brain volume loss, could you please let us know if there is any specific conditioning regimen you refer to when you say HSCT? Should the conditioning regimen to be used be decided based on what type of MS the patient has? How effective is Cladribine at turning off smouldering MS? If an IRT doesn't ablate the innate immune system, should it qualify as an IRT? Thanks and regards.
IRT refers to its effect on the adaptive immune system and not the innate immune system. I think anti-CD20 therapy that selectively targets B-cells could be used as an IRT.
Cladribine was tried in relapsing MS in the CLARITY trial and its impact on brain volume loss was disappointing; it reduced BVL by about 0.55% per annum. However, in the CIS or ORACLE trial, it reduced BVL to less than 0.2% per annum. Therefore it is about timing. The sooner you use and IRT the better. We think cladribine will tackle some components of smouldering MS because it is a small molecule and can penetrate the CNS>
When it comes to AHSCT the more ablative it is the more effective it is on average and the greater the adverse effects. In reality, our patients have to go with what is on offer in their local centre.
I’m in a similar situation so this is very interesting.
I had ON in 2015 and again in 2018 which led to my Dx. I then had a scan last year which showed 2 new lesions at which point I was offered Plegridy. I pushed for Ocrelizumab but this has just led to a year without treatment as my neurologist was initially unresponsive and later agreed to a 2nd opinion but wasn’t able to share the scans so no opinion was offered.
Apparently my case was discussed at the regional MDT but they decided against prescribing it. No information has been provided on the reasons for the decision and there’s no way to appeal. My latest scan shows another new lesions.
I feel totally helpless. I’ve researched the treatments and am happy to take the risks of a higher efficacy treatment. From my understanding I should be eligible for that treatment but have no way of accessing it. I’m also concerned that if I start Plegridy in the meantime I’m then on the escalation path with no way to get off.
Great article and interesting that most 'subjects' are pursuing the Alemtuzumab or HSCT route. On these, what is the theory behind halting the progression to SPMS and are there any studies that have tested this over a long period? is the data for HSCT different from Alemtuzumab on this particular disease marker?
The impact on progression in more advanced MS with all DMTs including alemtuzumab and AHSCT is relatively poor, i.e. it slows down worsening and does not stop it. A lot of AHSCT centres avoid offering AHSCT in SPMS unless there is a lot of ongoing inflammatory activity. The same applies to alemtuzumab.
I'm surprised to read that you consider NICE guidelines to be legal obligations! What about the times when it says you can't prescribe? As professionals do we not retain our right to treat according to our opinion and conscience, referring on to another specialist if need be? I do not think that a NICE determination compels me to produce a prescription.
Re: "I do not think that a NICE determination compels me to produce a prescription."
I agree, but you would have to refer the patient to someone else if that patient is eligible for a NICE approved treatment and they want to be treated with it. This is about the NHS having to provide the treatment, not the individual prescriber. In fact, only MSologists working at NHS England approved MS centres can prescribe alemtuzumab and the other licensed monoclonals in England.
I thought so too, but at a meeting 2 years ago a medicolegal barrister pointed out to us that the legislation underpinning the creation of NICE put this onus on the NHS to offer NICE approved medications if patients are eligible for them. How else would NICE, i.e. the government, be able to claim they have dealt with the postcode prescribing lottery? This is why NICE is such a powerful organisation.
Another excellent case study and encouragement. I didn't know that if you met the NICE criteria a neurologist has a legal obligation to prescribe. It might have saved me transferring from a risk averse neurologist and getting stuck on Fingolimod at my new centre. But fair dos through just about to start cladribine aftet a relapse. Neurologist number 1 would not have agreed
Well, this was a very good read.
It was my understanding that Lemtrada can not be prescribed as a first line therapy anymore, following the recent EMA recommendations. Did I get this wrong? If I got this right, what constitutes failure on other heDMTs like Tysabri? New MRI evidence of disease activity after 6 months of use? What about subjective feelings such as cognitive impairment, memory issues becoming more prominent and the like?
If you are eligible for natalizumab (Tysabri) you are eligible for alemtuzumab. You can just switch. The one caveat is if you are JCV positive and have been on natalizumab for longer than 12 months you need to be careful and make sure you don't have asymptomatic PML that can be carried over to alemtuzumab. This is why we bridge patients on fingolimod.
The following is the indication in the SmPC as you can see the second indication or RES can be 1st-line use.
4.1 Therapeutic indications
LEMTRADA is indicated as a single disease-modifying therapy in adults with highly active relapsing-remitting multiple sclerosis (RRMS) for the following patient groups:
• Patients with highly active disease despite a full and adequate course of treatment with at least one disease-modifying therapy (DMT)
OR
• Patients with rapidly evolving severe relapsing-remitting multiple sclerosis defined by 2 or more disabling relapses in one year, and with 1 or more Gadolinium enhancing lesions on brain MRI or a significant increase in T2 lesion load as compared to a previous recent MRI.
Please see https://www.medicines.org.uk/emc/product/5409/smpc#gref for more details.
Dear Sir, you mention that AHSCT and Lemtrada are more effective at turning off smouldering MS and slowing down brain volume loss, could you please let us know if there is any specific conditioning regimen you refer to when you say HSCT? Should the conditioning regimen to be used be decided based on what type of MS the patient has? How effective is Cladribine at turning off smouldering MS? If an IRT doesn't ablate the innate immune system, should it qualify as an IRT? Thanks and regards.
IRT refers to its effect on the adaptive immune system and not the innate immune system. I think anti-CD20 therapy that selectively targets B-cells could be used as an IRT.
Cladribine was tried in relapsing MS in the CLARITY trial and its impact on brain volume loss was disappointing; it reduced BVL by about 0.55% per annum. However, in the CIS or ORACLE trial, it reduced BVL to less than 0.2% per annum. Therefore it is about timing. The sooner you use and IRT the better. We think cladribine will tackle some components of smouldering MS because it is a small molecule and can penetrate the CNS>
When it comes to AHSCT the more ablative it is the more effective it is on average and the greater the adverse effects. In reality, our patients have to go with what is on offer in their local centre.
I’m in a similar situation so this is very interesting.
I had ON in 2015 and again in 2018 which led to my Dx. I then had a scan last year which showed 2 new lesions at which point I was offered Plegridy. I pushed for Ocrelizumab but this has just led to a year without treatment as my neurologist was initially unresponsive and later agreed to a 2nd opinion but wasn’t able to share the scans so no opinion was offered.
Apparently my case was discussed at the regional MDT but they decided against prescribing it. No information has been provided on the reasons for the decision and there’s no way to appeal. My latest scan shows another new lesions.
I feel totally helpless. I’ve researched the treatments and am happy to take the risks of a higher efficacy treatment. From my understanding I should be eligible for that treatment but have no way of accessing it. I’m also concerned that if I start Plegridy in the meantime I’m then on the escalation path with no way to get off.