Multiple sclerosis disease-modifying drugs: second line treatments

Most young people with Multiple sclerosis (MS), who are eligible for treatment, will be offered first line treatments. In certain situations, or if the first line treatments have not worked adequately, then your child may be offered the possibility of trying a second line medication. These medications, like the first line treatments, work by interacting with the immune system and calming the inflammation that is attacking the central nervous system.

There are currently two disease-modifying drugs (DMDs) used as second line treatment in relapsing-remitting MS – natalizumab and fingolimod. The treatments do not cure MS, but can reduce the number of relapses. More information about each of these drugs follows.

Natalizumab

Natalizumab (available under the brand name Tysabri®) is known to be very effective for MS treatment, and in trials has shown a 68 per cent decrease in the frequency of relapses and a 42 to 54 per cent delay in accumulation of disability. There have been no formal trials in children and young people with MS, but it is widely used for the same indications in adults and appears to work just as well if not better in children and young people.

It is ‘unlicensed’ for use in children. You can be assured that your doctor has only prescribed an ‘unlicensed’ medicine because he or she thinks that the medicine will benefit your child and no licensed alternative is available.

In MS, active immune cells pass cross from the blood into the brain and spinal cord and cause inflammation and damage. Natalizumab binds to these immune cells and prevents them entering the central nervous system and causing damage.

How is natalizumab given?

Natalizumab is given once every four weeks through a needle placed in a vein (intravenous or IV infusion). The whole process takes three to four hours once established. It will be given on the Neurology Day unit at GOSH. There will be some flexibility about the day you come to GOSH, but it is preferable not to delay significantly between treatments if possible.

Who should not take natalizumab?

People with any of the following should discuss using natalizumab with their doctor:

  • Hypersensitivity to natalizumab or any of its ingredients.

  • Pregnant, could be pregnant, planning to become pregnant or breastfeeding.

  • Existing Progressive Multifocal Leukoencepahlopathy (PML).

  • Immune system problems due to illness or previous immunosuppressant medicines taken.

What are the side effects of natalizumab?

Progressive Multifocal Leukoencepahlopathy (PML)

Natalizumab is generally well tolerated, but does have risks. The biggest risk is that if your child has previously been infected with a normally harmless virus called the JC virus, treatment with natalizumab increases the chance of getting a rare brain infection caused by the virus changing, multiplying and spreading. This infection is known as Progressive Multifocal Leukoencephalopathy (PML). PML in people who take natalizumab is associated with a high mortality affecting 22 per cent of people and high chance of severe disability affecting 50 per cent.

The risks of developing PML increase with the number of months on treatment over 24 months and whether your child has previously taken drugs to suppress the immune system, such as azathioprine, but not beta interferons or glatiramer acetate. Before starting treatment, your child will be offered a blood test to look for the anti-JC virus antibody and based on this you will be given more precise risks. If your child is JC virus negative, the risk is known to be extremely low, with a less than one in 9,000 chance of getting PML.

Allergic reactions

These occur in about four per cent of people. Symptoms can include: hives, itching, trouble breathing, chest pain, low blood pressure, dizziness, chills, nausea or flushing.

Infections

Natalizumab affects your immune system, and thus may increase your chance of getting an unusual or serious infection. This can include chicken pox, shingles and cold sores.

Liver injury

There is a small amount of evidence suggesting that natalizumab can cause liver injury. The current data suggests that this is rare, less than one in 1,000 chance. Your child will have a blood test to check liver function before starting natalizumab and we will continue to monitor it with periodic blood tests while you are on the treatment.

Other side effects

These include headache, feeling tired, urinary tract infections, joint pain, feeling tired, depression, diarrhoea, colds and coughs. 

Natalizumab and other medicines

Some medicines can react with natalizumab, altering how well it works. Always check with your doctor or pharmacist before giving your child any other medicines, including herbal or complementary medicines. Natalizumab must not be taken alongside other medicines listed below

  • First line DMDs – beta interferon or glatiramer acetate

  • Immunosuppressant medicines either taken currently or in the past

Fingolimod (Gilenya®)

Fingolimod is known to be very effective for MS treatment and in trials has shown a 58 per cent decrease in the frequency of relapses and a delay in accumulation of disability by about a third. There have been no formal trials completed in children and young people with MS.

It is ‘unlicensed’ for use in children. You can be assured that your doctor has only prescribed an ‘unlicensed’ medicine because he or she thinks that the medicine will benefit your child and no licensed alternative is available.

Fingolimod binds to the surface of white blood cells in the blood, and these cells are then trapped in the lymph glands, which prevents the immune cells from crossing into the central nervous system and causing inflammation and damage.

How is fingolimod given?

Fingolimod is taken once daily by mouth as a capsule. For information on how to help your child takes medicines in capsule form, please see our short video, which you can also watch on YouTube.

Who should not take fingolimod?

People with any of the following should discuss using fingolimod with their doctor:

  • Hypersensitivity to fingolimod or any of its ingredients.

  • Pregnant, could be pregnant, planning to become pregnant or breastfeeding.

  • Existing infection such as hepatitis or tuberculosis.

  • Existing liver problems.

  • Immune system problems due to illness or previous immunosuppressant medicines taken.

What are the side effects of fingolimod?

Irregular or slow heart rate

Fingolimod is known to cause significant slowing of the heart rate and blood pressure problems when first given in a small percentage of people. Any irregularity of heartbeat normally returns to normal in a day and blood pressure to normal within a month of treatment.

On account of these side effects, your child will need to have an ECHO before the first dose, which will be given in hospital while they are on a heart monitor for a minimum of six hours. If there are no signs of an irregular or slow heart rhythm, then your child will be able to go home that day. Due to the effect of the first dose of fingolimod on the heart, it is very important to take it every day without having breaks. If your child stops taking treatment for any length of time, it will need to be started again in hospital.

Macular oedema

Figolimod is known to cause swelling at the back of the eye. This is rare, affecting less than one per cent of people taking the medicine. Your child will have an eye examination before treatment and regularly during treatment.

Blood changes

Fingolimod treatment can rarely cause the white blood cells to drop or the liver to be affected. Your child’s blood will thus need to be monitored every few months.

Infections  

Fingolimod affects the immune system, and thus may increase the chance of your child getting an unusual or serious infection. This can include chicken pox, shingles and cold sores. Before starting treatment, your child will need to have a test to check their chicken pox status.  

Other side effects

These include headache, back pain, feeling tired, skin rash, joint pain, eye pain, slight rise in blood pressure, depression and mood change, diarrhoea, colds and coughs. 

Fingolimod and other medicines

Some medicines can react with fingolimod, altering how well it works. Always check with your doctor or pharmacist before giving your child any other medicines, including herbal or complementary medicines. Fingolimod must not be taken alongside other medicines listed below.

  • first line DMDs – beta interferon or glatiramer acetate

  • immunosupressant medicines either taken currently or in the past

  • medicines that slow the heartbeat

  • medicines for irregular heartbeat

  • certain antibiotics and antifungal medicines

Important information

  • As natalizumab and fingolimod affect your child’s immune system, they should not be given any ‘live’ vaccines. The ‘killed’ or inactivated polio vaccine should be used instead of the ‘live’ form in patients taking natalizumab or fingolimod. Ideally, your child should have completed their scheduled immunisations before taking natalizumab or fingolimod. Your other children should be immunised according to the usual schedule but they should also receive the ‘killed’ or inactivated polio vaccine. If you have any questions about immunisations, please ask your doctor.

  • Store all medicines in a safe place where children cannot reach them.

  • If your doctor decides to stop or change treatment, return any unused DMDs to the pharmacist. Do not flush them down the toilet or throw them away.

  • If you forget to give your child a dose and it is within a few hours of when the dose was due, give it as soon as you remember. Otherwise, do not give this dose but take the next dose when it is due. Do not give a double dose.

Compiled by: 
The Neuroimmunology Centre in collaboration with the Child and Family Information GroupThis information does not constitute health or medical advice and will not necessarily reflect treatment at other hospitals.
Last review date: 
January 2014
Ref: 
2013F1583

Disclaimer

Please read this information sheet from GOSH alongside the patient information leaflet (PIL) provided by the manufacturer. If you do not have a copy of the manufacturer’s patient information leaflet please talk to your pharmacist. A few products do not have a marketing authorisation (licence) as a medicine and therefore there is no PIL.

For children in particular, there may be conflicts of information between the manufacturer’s patient information leaflet (PIL) and guidance provided by GOSH and other healthcare providers. For example, some manufacturers may recommend, in the patient information leaflet, that a medicine is not given to children aged under 12 years. In most cases, this is because the manufacturer will recruit adults to clinical trials in the first instance and therefore the initial marketing authorisation (licence) only covers adults and older children.  

For new medicines, the manufacturer then has to recruit children and newborns into trials (unless the medicine is not going to be used in children and newborns) and subsequently amend the PIL with the approved information. Older medicines may have been used effectively for many years in children without problems but the manufacturer has not been required to collect data and amend the licence. This does not mean that it is unsafe for children and young people to be prescribed such a medicine ‘off-licence/off-label’. However, if you are concerned about any conflicts of information, please discuss with your doctor, nurse or pharmacist.