Symptom management for adult males and update on adult BMT in UK

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1 Symptom management for adult males and update on adult BMT in UK Robin Lachmann National Hospital for Neurology and Neurosurgery 12:05 Dr Robin Lachmann- Symptom management for adult males and update on adult BMT in the UK 1

2 Bladder Symptoms in AMN JIMD Rep. 2015;22:77-83 Bladder symptoms are common in women and men with ALD, which have been covered already. There is a lot of treatment available for these, as long as they are reported. It is important to treat these symptoms early, patients often wait to long with these and other symptoms before seeking help. 2

3 Bowel symptoms Sexual function Bowel symptoms can also occur, including constipation of faecal incontinence and urgency. Nerve stimulation and exercises can also be helpful. Sexual function can be affected, many treatments exist for this too and can be helped by a urologist. 3

4 Spasticity BMJ 2014;349:g4737 Leg problems such as spasticity; a combination of stiffness and weakness in the muscles of the legs; cause characteristic walking difficulties. This is treatable at a spasticity clinic by specialists. This is a common symptom of many diseases, and will be managed in much the same way regardless of the underlying cause. Treatment aims to relieve pain and discomfort, reduce spasms, improve posture through physiotherapy, reduce burden of care and improve hygiene. Body image and self esteem can be helped by treatment, as well as reducing the risk of pressure sores. 4

5 Non-drug interventions Stretching and splinting Postural management and standing Exercises Functional electrical stimulation BMJ 2014;349:g4737 The treatment options include drug and non-drug alternatives, with the non-drug option involving physiotherapy. There is not enough physiotherapy in the NHS, it is geared towards a 6 week intensive course aimed at recovery from injury, before the patient is left to manage their own physiotherapy. This is not ideal for long term neurological conditions. Physiotherapy and non-drug resolutions for spasticity are: Stretching and splinting Postural management in standing: Maintaining functions is very important, even those in a wheelchair should spend some of the day on their feet even if they are not weight-bearing in order to prevent contractures: fixed joint issues in which the muscles can no longer straighten out. Exercising as much as possible Functional electrical stimulation, used to combat a delay in signals from the brain telling the legs to move, by bringing the toes up as the leg swings, to prevent the toes from catching on the floor 5

6 Drug interventions Oral anti-spasticity drugs BMJ 2014;349:g4737 Interventions using drugs are tablets to reduce stiffness 6

7 BMJ 2014;349:g4737 Baclofen- very effective in reducing spasms stiffness in muscles, but this can expose the weakness of the muscle, making mobility worse. This is the drug which is often used first. Tizanidine is a second line agent, although it is not as effective and has side effects which do not include weakness Dantrolene is not used much any more Other drugs can help with pain and numbness 7

8 Drug interventions Oral anti-spasticity drugs Botulinum toxin Intrathecal baclofen BMJ 2014;349:g4737 Botulinum toxin injections paralyse muscles, which will make them weaker Baclofen can also be administered directly into the spinal cord when spasticity is very severe. 8

9 Psychological Support BMJ 2014;349:g4737 Psychological support is also very important, this is also not as readily available as needed. 9

10 HSCT for Adults in UK BMJ 2014;349:g

11 Bone marrow transplants for adults in the UK: 11

12 Bone marrow transplants are regarded as specialist treatments in the UK, commissioned by NHS England. NHS England will currently commission bone marrow transplants for conditions which the British Society of Blood and Marrow Transplantation have recommended it for. These recommendations include inherited metabolic diseases for children (under 18), including ALD, but there are no inherited metabolic diseases included in the recommended list for adults, so the NHS will not pay for adults with ALD to have bone marrow transplants. 12

13 Attempts to have ALD added to this list, including asking NHS England if changes to the list would be permitted, would be a start. Is there enough evidence to do this? 13

14 Engelen et al. Orphanet Journal of Rare Diseases 2012, 7:51 Adult patients who may be suitable for transplant are those in their 20s presenting with no signs of AMN but with ALD. At the moment, these patients are not eligible for treatment even if they were caught early enough. Patients with AMN also developing cerebral ALD could also be suitable for transplant (around 20% of men with AMN are at risk of cerebral ALD over a period of 10 years). These two groups of adults are those we would hope to be considered for bone marrow transplants. There are men in these groups who have had bone marrow transplants- especially those with AMN. 14

15 Engelen et al. Orphanet Journal of Rare Diseases 2012, 7:51 15

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17 A German study looked at 13 men 3 years after bone marrow transplant in order to study the benefits of the treatment. 17

18 After 3 years, 8 of the 13 men have survived. 3 of the 6 deceased patients died of complications in the transplant itself, the other 3 died of progression of the disease. 18

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20 This is a much worse result than similar trials in children, due to the later progression of the disease (shown in higher EDSS rates before transplant). This shows that chances of complications in the bone marrow transplant are much higher as AMN progresses. For those who survived the 3 years, EDSS scores in many cases showed a significant change; very few remained stable, most saw continued progression of the disease. 20

21 From this data, further criteria were established to show who is most likely to do well after transplant. 21

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23 Preliminary recommendations for HSCT in ACALD patients: Disease Males at risk of developing ACALD should be routinely monitored by a multidisciplinary team (neurologists, metabolic physicians and transplant haematologists) in specialized centres. Potential family donors should be identified in advance to save time once inflammatory cerebral demyelinating lesions (i.e. with contrast enhancement) are identified on brain MRI. Stable neurocognitive function prior to transplant and limited AMN symptoms (EDSS<6) are favourable outcome parameters. Patients with bilateral involvement of the internal capsule on brain MRI do not seem to benefit from HSCT. 23

24 Preliminary recommendations for HSCT in ACALD patients: Procedure Stem cell source: bone marrow from a matched related or unrelated donor (59/10 HLA-match confirmed by highresolution typing) is preferred over peripheral blood stem cells or cord blood HSCT procedure: busulfan based full intensity or myeloablative conditioning regimens should be used, combined with serotherapy (e.g. antithymocyte globulin) to promote engraftment and limit GVHD. All efforts should be made to prevent fever due to serotherapy or infections, which may be associated with acute neurological deterioration. Patients should be treated in experienced transplant centres and registered with the European Group for Blood and Marrow Transplantation (EBMT), the Center for International Blood and Marrow Transplantation Research (CIBMTR) or equivalent transplant registries. 24

25 Routes to obtaining reimbursment 1. NICE appraisal 2. NHSE Clinical Commissioning Policy There are 2 means of gaining NHS approval: NICE approval- not appropriate here for such a rare condition; or a clinical commissioning policy- complicated. 25

26 A clinical commissioning policy is a document that defines access to a service, drug or technology for a particular group of patients and is developed to ensure consistency in access to treatments nationwide. NHS England will only give priority to treatments or interventions where the intervention is likely to offer equal or greater benefit than other forms of care routinely commissioned by the NHS for the same patient group While considering the benefit of stimulating innovation, NHS England will not confer higher priority to a treatment or intervention solely on the basis it is the only one available The intervention must be available to all patients within the same patient group, other than for clinical contra-indication This policy defines access to a technology for a group of patients to ensure consistency of access. Results from the German study and similar studies would be crucial here to develop a protocol on exactly who would be most likely to benefit from the treatment, in order to define the specific patient group and ensure this consistency of access. 26

27 Prioritisation Principles NHS England will normally only accord priority to treatments or interventions where there is adequate and clinically reliable evidence to demonstrate clinical effectiveness NHS England will normally only accord priority to treatments or interventions where there is measureable benefit to the relevant group of patients NHS England may agree to fund interventions for rare conditions where there is limited published evidence on clinical effectiveness The treatment or intervention should demonstrate value for money NHS England will only give priority to treatments where it is likely to offer greater benefit than other forms of care. This is not more likely when there are no other treatments available, this does not mean priority will be given. 27

28 Individual Funding Requests Individual Funding Requests are an alternative. Doctors make an individual request to NHS England requesting a patient be given the treatment. The request must show that there is something exceptional about this patient; they would benefit where others wouldn t because they meet the criteria shown in the study- e.g. few/no symptoms of AMN, less advanced condition. This individual request has been successful once this year, it can only happen a couple of times a year before the NHS starts thinking that a policy is needed. At the moment, these individual requests are the only way to get a bone marrow transplant. Creating a protocol on who would be suitable for bone marrow transplant and who would not benefit from this is vital to give adult males with ALD access to bone marrow transplants. This would also be useful for New Born Screening, because NBS does not only reveal ALD in the child but also in the family, in related adult males without a diagnosis. A policy is needed for these people. 28

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