MS treatment Zinbryta (daclizumab) withdrawn worldwide amid safety concerns

Disease modifying therapy daclizumab (Zinbryta) has been withdrawn from sale worldwide. Its manufacturers took the decision after reports that a number of people taking the treatment developed serious inflammatory brain disorders. That’s how the news was announced on the MS Society’s website.

In the UK, the treatment will no longer be available via the country’s National Health Service (NHS).

zinbryta withdrawnTo me, though, the drug’s withdrawal after safety concerns raises an important question. Just how good are our procedures for approving and licensing new drugs? Despite supposedly stringent procedures, including clinical trials, this drug was given the green light. But, so soon after approval, serious side effects have been reported.

This must surely mean that the approval process was not sufficiently strict. Maybe, the pressure on the need for approval somehow managed to overcome the necessity of due diligence.

zinbrytaSo, what has happened? Manufacturers Abbvie and Biogen have withdrawn daclizumab from the market. This was because of a number of cases of serious brain inflammation) (encephalitis and meningoencephalitis). Already, the European Medicines Agency (EMA) has started an urgent review of the drug and these cases.

A statement on Biogen’s website says: “Patient safety is the top priority for Biogen and AbbVie.

“Given the nature and complexity of adverse events being reported, characterizing the evolving benefit/risk profile of Zinbryta will not be possible going forward given the limited number of patients being treated. Therefore, Biogen and AbbVie believe it is in the best interest of patients to voluntarily withdraw worldwide marketing authorizations for Zinbryta.

Having Zinbryta injections? What to do now

“Biogen will continue to work collaboratively with regulatory authorities and with healthcare providers in their management of Zinbryta patients.”

As part of the withdrawal, all clinical trials involving the treatment will also be stopped. People in those clinical studies who have any question should contact the doctor treating them in their study.

The EMA advises that:

  • • anyone currently taking Zinbryta should not stop without first talking to their neurologist or MS nurse
  • doctors should review anyone currently taking Zinbryta and discuss switching to an alternative treatment as soon as possible. (The National MS Society in the US says that safety monitoring should be continued, adding “According to the medication guide, this would include monthly blood tests to monitor liver function for up to six months after the last dose.”)
  • no one should begin taking Zinbryta

Zinbryta was approved in 2016 for use as a disease modifying therapy (DMT) for people with relapsing remitting MS. However, that approval was only for anyone who continued to have relapses despite having tried at least two other DMTs.

One good thing about the decision to withdraw Zinbryta is that the manufacturers took action themselves and did not wait for regulators to act.

For anyone living in the UK, the MS Society says: “If you’re concerned by this news, you can call our MS Helpline on 0808 800 8000 (Monday to Friday 9am-7pm) or email helpline@mssociety.org.uk for information and support.”

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Affiliate disclaimer: This affiliate disclosure details the affiliate relationships of MS, Health & Disability at 50shadesofsun.com with other companies and products. Read more.

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50shadesofsun.com is the personal website of Ian Franks, a freelance medical writer and editor for various health information sites. He enjoyed a successful career as a journalist, from reporter to editor in the print media. He gained a Journalist of the Year award in his native UK. Ian received a diagnosis of MS in 2002 and now lives in the south of Spain. He uses a wheelchair and advocates on mobility and accessibility issues.

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Note: Health-related information available on 50shadesofsun website is for your general knowledge only. It is not a substitute for medical advice or treatment for specific medical conditions. I am not a doctor and cannot and do not give you medical advice. You should seek prompt medical care for any specific health issues. Also, consult a doctor before starting a new diet or exercise programme. Any opinions expressed are purely my own unless otherwise stated.

Zinbryta use restricted in Europe after a death and four serious liver injuries

The European Medicines Agency (EMA) has restricted the use of multiple sclerosis drug Zinbryta. The agency took action after a patient died from liver injury (fulminant liver failure). The patient was in an ongoing observational study. Four cases of serious liver injury have also been reported.

We are all likely to experience some side effect of any medication we take, whether for multiple sclerosis or some other disease. Most of us, hopefully, will only have minor problems, if any, but some will be badly affected.

All medicine manufacturers provide a list of their drugs’ side effects, from major to minor, from common to rare. Pharmaceutical companies provide this information for the benefit of patients, not just healthcare professionals.

And, we need to take those lists seriously. After all, it is our health that is on the line.

I always pay close attention to news of new drugs approved for use in the treatment of MS. But, no matter how good the claimed benefits appear, I focus on the possible side effects admitted by the manufacturer.

Now, that is not to say that all disease modifying therapies (DMTs) are bad for us. But we need to balance benefits against the disadvantaged of possible side effects. Everyone must make their own decision.

Such decisions are personal. I have never accepted any DMT.

Zinbryta – liver damage risk known when approved

zinbrytaZinbryta (daclizumab) is one such DMT and its side effects include the risk of liver damage. The EU knew this when it approved the drug in July 2016. In fact, it put several measures in place to manage this risk. These included the requirement to monitor liver function and provide educational materials to healthcare professionals and patients on the risk of liver damage.

Now, though, a year later, the EMA has provisionally restricted the use of the medicine to:

  • patients with highly active relapsing remitting MS (RRMS) that has failed to respond to certain other treatment, and 
  • patients with rapidly evolving relapsing MS who cannot be treated with other medicines.

In addition, doctors must not give the medicine must to patients with liver injury.

It is not recommended for patients with autoimmune conditions other than MS. Medical professionals should be cautious when the give Zinbryta together with medicines that can damage the liver. Doctors are advised to monitor the liver function of patients to whom they give the medicine. They should closely watch patients for signs and symptoms of liver injury.

The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) has issued these provisional recommendations as a precaution and to ensure that Zinbryta continues to be used as safely as possible while a review of its liver safety is ongoing.

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Affiliate disclaimer: This affiliate disclosure details the affiliate relationships of MS, Health & Disability at 50shadesofsun.com with other companies and products. Read more.

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50shadesofsun.com is the personal website of Ian Franks, a Features Writer with Medical News Today. He enjoyed a successful career as a journalist, from reporter to editor in the print media. He gained a Journalist of the Year award in his native UK. Ian received a diagnosis of MS in 2002 and now lives in the south of Spain. He uses a wheelchair and advocates on mobility and accessibility issues.

 

Why are DMTs – Drugs to treat MS – Resisted by so Many?

Many people with multiple sclerosis await the launch of each new disease modifying therapy (DMT), hoping it will bring some improvement.

Meanwhile, a significant number of those in the same situation seem to ignore a new drug and carry on regardless. But why?

dmts

Different DMTs for MS can be infusions, injectables, or tablets.

Well, there are a number of reasons; let’s take a look at a few of them:

  • The newly diagnosed often delay starting treatment because they are in denial or just decide to ‘wait and see’ how the disease develops.
  • Very many of us dislike taking medications of any sort, for any ailment.
  • Others say ‘no’ after researching possible side effects before they decide that they may be riskier than the disease itself.
  • Some have a type of MS for which DMTs have little or no benefit.

Of course, there are other reasons too, such as costs, and I am not decrying those.

I fully understand the ‘wait and see’ approach, especially at diagnosis, when symptoms may not be too bad. But research tells us that it is one of the worst choices that can be made. And that is equally true of clinically isolated syndrome (CIS) that can lead to MS.

DMTs: Better to start treatments early

Healthline.com explains: “Experts recommend starting one of the DMTs approved by the Food and Drug Administration as soon as a diagnosis is made. A study published in the Journal of Neuroscience Nursing, found that patients with MS or CIS benefit from starting treatment the first time they experience an event suggestive of MS.”

It continues: “Other research has found that delays in treatment, even in those with CIS, may result in more severe disability and a poorer response to treatment with DMTs later on.”

I think most of us resist taking ‘unnecessary’ medications and there is nothing wrong with that. It’s just a case of recognising, in consultation with your doctor, which treatments are needed and which aren’t.

Now, let us turn to the vexed issue of side effects. All drugs, not just ones to treat MS, have their own list of both common and rare side effects. I recommend you discuss this with your doctor, to ensure the benefits are worth any risk. The ultimate decision, however, is yours; it is your body.

Not every type of MS responds to every DMT. Most are suitable for the relapsing form of the disease where they work to prevent relapses. Relapsing patients who go on to develop Secondary Progressive MS often continue with the same drugs. Currently, nothing exists that is more suitable without having too high a risk.

For primary progressive MS patients, there is a new DMD that is now approved as a treatment in the USA. The drug is ocrelizumab, brand name Ocrevus.

DMTs for me?

I am frequently asked what drugs I take for MS. The answer, perhaps strange but nevertheless true, is ‘none’. In fact, in the 15 years since diagnosis, I have never been offered any drug treatment. Yes, I have pills to treat various symptoms but nothing for MS itself.

To be fair, though, I do check out each new drug and its side effects and there isn’t one that I’d be happy to take. A serious side effect, death, may be rare but it is final.

Enough said!

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Affiliate disclaimer: This affiliate disclosure details the affiliate relationships of MS, Health & Disability at 50shadesofsun.com with other companies and products. Read more.

* * * * *

50shadesofsun.com is the personal website of Ian Franks, who has enjoyed a successful career as a journalist, from reporter to editor, in the print media. During that career he gained a Journalist of the Year award in his native UK. Diagnosed with MS in 2002, he continued to work until mobility problems made him retire early in late 2006. He now lives in the south of Spain. Besides MS, Ian is also able to write about both epilepsy and cardiovascular matters from a patient’s perspective. Besides that, he is a keen advocate on mobility and accessibility issues.

New MS drug approved in USA and Europe

euro agencyA new disease modifying treatment is being considered for use in the UK following it being approved in the USA and Europe.

Already approved by America’s Food and Drug Administration (FDA), daclizumab, known as Zinbryta, has now been given the nod by the European Medicines Agency (EMA). The agency has recommended that the drug be licensed to treat people with relapsing forms of MS.

The UK’s National Institute for Health and Care Excellence (NICE) is now going to conduct an appraisal before deciding whether or not to make this treatment available on the NHS in England and Wales.

Daclizumab is injected once a month and works by reducing the number of immune cells thought to contribute to myelin damage seen in MS.  However, like all medicines, it does have the risk of side effects, some extremely rare, and not everybody gets them. Side effects include fatigue, stomach upset, infections, and impaired liver function. Serious but rare effects include what are referred to by manufacturer Biogen as ‘fatal events’.

Indeed, the prescribing information includes a boxed warning about the potential for severe liver injury, including life-threatening and fatal events. For “fatal events,” read “death.”

It also highlights other important risks of Zinbryta treatment, including inflammation of the colon (non-infectious colitis), skin reactions, and enlargement of lymph nodes (lymphadenopathy). Additional warnings include hypersensitivity reactions (anaphylaxis or angioedema), increased risk of infections, and symptoms of depression and/or suicidal thoughts. As if people with MS are not depressed already!

According to data from a phase 3 trial involving 1,841 people with relapsing remitting MS has indicated daclizumab to be more effective than beta-interferons in reducing relapses. The trial showed after 96 weeks, 73% of participants taking daclizumab were relapse-free, compared to 59% of participants taking beta-interferon.

Britain’s MS Society is planning to submit evidence to NICE as part of its Treat Me Right campaign that is calling for all licensed MS treatments to be available on the NHS to everyone eligible for them.

Treat Me Right

The MS Society is fighting for the right treatment at the right time for people with MS, whatever their situation, wherever they live.

It believes that people with MS should have fair and equal access to treatments wherever they live. But, at the moment, this isn’t happening. The aim of the campaign is to change that.

The society says: “We’re campaigning to make these goals a reality:

  • All licensed MS treatments available on the NHS to everyone eligible for them
  • Regular reviews of treatment and care by MS specialists for everyone with MS
  • Accessible information about treatment options, and support to be equal partners in decision-making, available to all people with MS

“We hope they’ll help people with MS get the right treatment at the right time.”

 

MSNT strapline copy

 

 

Epilepsy drug being tested for multiple sclerosis use

phenytoin

News that the generic drug phenytoin, used as an anti-convulsant to treat epilepsy, is being tested as a treatment for certain types of problems associated with multiple sclerosis, caught me by surprise.

Although I am not a doctor or scientist, I can speak with some authority about this drug because I was prescribed it for some 30 years.

This is because, in addition to MS, which was diagnosed 14 years ago, I also have had epilepsy since the age of 19.  Phenytoin or Epanutin as it is more frequently known in the UK (and Dilantin in the USA and Canada) was the drug of choice, accompanied by phenobarbitone.

Thankfully, I have been free of seizures for 40 years now but after undergoing tests, when MS was diagnosed, was told that I still had epilepsy as well.

At that time, my neurologist described phenytoin as a very old treatment and changed my prescription to Lamotrigine – which I find works far better than phenytoin ever did. With the former, my right arm sometimes shook as a prelude to a seizure. This made me stop whatever I was doing and physically walk away from it. That avoided many seizures. Since my prescription was changed to Lamotrigine, those ‘warnings’ have never been there but neither have the seizures.

However, if the trials prove positive to treat trigeminal neuralgia or other painful sensations (dysaesthesia) that would be great

Phenytoin has been studied as a potential neuroprotective drug. Results of a phase II study of 82 people with optic neuritis were announced at a conference in April 2015 and published in the Lancet Neurology in January 2016. Researchers found that people who had been treated with phenytoin over three months showed 30% less damage to nerve cells in the retina than people taking a placebo.

As with all drugs, phenytoin has side effects and, while they may not be known yet with regard to MS patients, it cannot be wise to not acknowledge the known side effects experienced by other people.

These include constipation, mild dizziness, mild drowsiness which are normally transitory and will pass as an individual adjusts to the medication.

From an MS patient’s point of view, phenytoin may affect an individual’s ability to metabolise Vitamin D and a GP may advise taking supplements. Phenytoin may reduce the effectiveness of some oral contraceptives and can interact with fluoxetine (Prozac), paroxetine (Seroxat) and St John’s wort. People should not take it if they have liver dysfunction and should also be avoided during pregnancy or whilst still breastfeeding.

One side effect not included above is gum recession. Gingival enlargement, (also termed gingival overgrowth, hypertrophic gingivitis, gingival hyperplasia, or gingival hypertrophy, and sometimes abbreviated to GO), is an increase in the size of the gingiva (gums). It is a common feature of gingival disease. Gingival enlargement can be caused by a number of factors, including inflammatory conditions and the side effects of certain medications.

Phenytoin is one such medication and dentists have told me that my 30 years on phenytoin is the reason I now have more teeth on dentures than my own real ones. Gingival overgrowth is a common side effect of phenytoin, termed ‘Phenytoin-induced gingival overgrowth’ (PIGO).1

 

1 Arya, R; Gulati, S (March 2012). “Phenytoin-induced gingival overgrowth.”. Acta neurologica Scandinavica 125 (3): 149–55. doi:10.1111/j.1600-0404.2011.01535.x. PMID 21651505.