Humira and Ozurdex finally approved for treating non-infectious uveitis in England and Wales

Finally after months of consultations, NICE has published its guidance and recommendations for adalimumab (Humira) and dexamethasone implants (Ozurdex).

The general information for the public can be found:  https://www.nice.org.uk/guidance/ta460/informationforpublic:

We suggest you may also wish to read Recommendations and then, if you want to know more, turn to the Summary from page 19 onwards and finish by reading the ‘Implementation’, section 5 on page 27.

Please also be aware that the process of obtaining Humira (adalimumab) injection and Ozurdex (dexamethasone intravitreal implant) treatment won’t suddenly speed up in England and Wales because the NICE guidance has been published. However, having NICE guidance should make it much easier to obtain Humira or Ozurdex treatment if your consultant says you need it.

 

https://www.nice.org.uk/guidance/ta460/informationforpublic

NICE – Uveitis (non-infectious) – adalimumab and dexamethasone [ID763]

It has been a long time coming but at last you can now  access all the committee papers, presentations and the draft NICE guidance for adalimuab injection (Humira®) and dexamethasone implant (Ozurdex®) as all the documents are now available on the NICE website: https://www.nice.org.uk/…/indevelopme…/gid-ta10007/documents

This multiple technology appraisal is a long drawn process and  BUS has been involved in this from the start in June 2015.   Since then we submitted an organisation statement and provided a patient expert to give the patient’s perspective on Humira.    We, along with RNIB and Olivia’s Vision have provided the patient perspective as we feel it is very important that these totally different technologies are available for people with sight threatening posterior uveitis.

There are many pages involved in the committee papers, but below we provide an index to help you find your way around.

As an organisation we will be providing our comments about draft guidance to try and get it improved and as members of the public you are also free to submit comments via the website.  The committee will meet on the 12th April to consider the proposal and the guidance will then be published in July 2017

We have often felt swamped by all the NICE paperwork. Under the webpage heading ‘Appraisal Consultation’ you will see links to the ‘appraisal consultation document’ and to the committee papers.

There are 684 pages of committee papers, but below we provide an index to help you find your way around. The appraisal consultation document contains the draft recommendations for the use of Humira and Ozurdex and this is fortunately considerably shorter. As an organisation, we will be providing our comments about the draft recommendations to try to get them improved. As members of the public, you are also free to submit your comments on the appraisal consultation document via the website.

The NICE appraisal committee will meet again on the 12th April to consider all the comments received on the appraisal consultation document. The NICE guidance will then be published in July 2017 as a ‘final appraisal determination’.

NICE committee papers, March 2017: page index to the 684 pages

 p3: ‘pre-meeting briefing’ done for committee members before February 15th 2017 meeting (includes useful notes linked to the assessment report, eg, p9: a treatment pathway provided by the clinical advisors).

  • p65:’matrix of consultees and commentators’ (issued February 2016).
  • p61: ‘final scope’ (issued June 2016).
  • p69: ‘Assessment Group Report’ (the economic modelling done by Sheffield; issued 30th November 2016).
  • p298: AbbVie’s response to the assessment group report.
  • p318: Allergan’s response to the assessment group report.
  • p326: BUS’s response to the assessment group report.
  • p328: Olivia’s Vision’s response to the assessment group report.
  • p330: RNIB’s response to the assessment group report.
  • p350: Assessment Group response to RNIB comments.
  • p351: Assessment Group response to Olivia’s Vision comments.
  • p352: Assessment Group response to BUS comments.
  • p357: Errata to the Assessment Group Report (all highlighted in red).
  • p431: AbbVie’s submission to NICE (August 19th 2016).
  • p489: Allergan’s submission to NICE (August 19th 2016).
  • p598: BUS’s submission to NICE (summer 2016).
  • p610: Olivia’s Vision’s submission to NICE (summer 2016).
  • p624: RNIB’s submission to NICE (summer 2016).
  • p640: NHS England’s submission to NICE (includes references to sirolimus).
  • p648: Prof Phil Murray’s submission to NICE.
  • p656: Sri Sharma’s submission to NICE.
  • p663: Ali Mapstone’s patient expert statement to NICE.
  • p671: Maxine McCarthy’s patient expert statement to NICE.
  • p681: Nicola Symes’s NHS England statement to NICE.

 

 

 

Humira formulation change

The formulation of Humira (adalimumab) prefilled pens and prefilled syringes is being changed. The changeover from the original formulation to the new formulation is being rolled out in different countries at different times.

Humira’s original formulation is known to cause stinging on injection. AbbVie, the makers, have been working on a new formulation to try to reduce this. They have removed citrate and some of the other extra ingredients from the original formulation used in the prefilled pens and prefilled syringes. This also means that the volume of liquid in each pen and syringe can be reduced, so the new formulation pens and syringes contain 40mg adalimumab in 0.4ml, compared with the original formulation pens and syringes which contain 40mg adalimumab in 0.8ml. The actual adalimumab dose in the new formulation pens and syringes is exactly the same as in the original formulation pens and syringes.

The situation as at February 2017 is:

UK: new formulation pens and syringes were introduced in July 2016 (the paediatric 40mg/0.8ml vials are still supplied in the original formulation).

US: original formulation is still in use: pens, syringes and paediatric vials.

Canada: original formulation is still in use: pens, syringes and paediatric vials. Launch of new formulation pens and syringes is planned for 2017.

Other countries: no information.

If birdshotters using Humira could let BUS know when their country changes over to the new formulation, we would be very grateful. We would also like to hear of your experiences with the new formulation, particularly if you have previously used the original formulation.

Better options for treating Birdshot

New research funding partnership between Fight for Sight and Birdshot Uveitis Society

Birdshot uveitis is a rare autoimmune disorder that has the potential to blind. It’s notoriously hard to treat. The UK’s main eye research charity Fight for Sight is partnering with Birdshot Uveitis Society to try to change that with new grants to researchers in London and Birmingham, to fund pioneering research that could lead to better treatments.

In birdshot, which is strongly linked to the gene HLA-A29, the immune system attacks two critical structures at the back of the eye: the retina and the choroid. The retina contains the photoreceptor cells that detect light and send visual signals to the brain, while the choroid is a layer of blood vessels that supplies the retina with oxygen and nutrition. When this supply is interrupted as during an inflammatory immune response, the photoreceptors can’t function normally.

Current options for treatment are limited to steroids and drugs to suppress the immune system. However in the long term these can cause sight-threatening complications such as cataract and glaucoma. We need some better options.

Stem cells from patients

Dr Anai Gonzalez Cordero at UCL Institute of Ophthalmology is leading one of the two new studies. The team will study a layer of cells in the retina called the retinal pigment epithelium (RPE) in tissue developed from birdshot patient stem cells.

“Subtle changes to RPE can be seen in some patients during the early stages of birdshot. This is not an obvious feature of the condition but current examination methods are limited, identifying only severe dysfunction,” says Dr Gonzalez Cordero.

“We do know that RPE can modulate the choroid and that RPE cells show HLA-A29 gene activity. Almost everyone with birdshot has a particular variation of this gene. Post-mortem tissue from birdshot patients is both scarce and unsuitable for detailed analysis. However we can develop mature RPE in the lab from stem cells derived from blood of living patients. This will allow us to explore the role of RPE in detail as well as providing a much-needed test bed for future treatments that can also be used by other researchers in the field.”

Iron overload is treatable

Dr Graham Wallace at the University of Birmingham will lead the second study. Here the focus is on genetic control of iron levels in birdshot.

“Iron is essential in the retina for photoreceptor cell function and is generally controlled by iron-regulating proteins. However free iron is highly toxic for photoreceptors, leading to an increase in oxidative stress. Iron is also involved in inflammation as it is essential for the proliferation of immune cells,” says Dr Wallace.

“Given a recent association between HLA-A29 and HFE H63D – a gene implicated in patients with iron overload – we think this could be an important route to explore with regard to birdshot. Iron overload is treatable and so may give us other options.”

Dr Dolores Conroy is Fight for Sight’s Director of Research. She says: “Understanding the root causes of birdshot is ultimately what will lead us to targeted, effective treatments. The Sight Loss and Vision Priority Setting Partnership tells us that this is what’s important to patients and so we are delighted to partner with Birdshot Uveitis Society to see the priorities addressed.”

Annie Folkard, a founder of the Birdshot Uveitis Society, said: “We are excited to support this innovative research. Studies likes these give our members great hope that in the future, improvements will be made to the current toxic treatments. Maybe even a cure will be found.”

Treatment with adalimumab (Humira®) now available in Wales

There is progress in Wales regarding an interim policy, published October 2016, for adalimumab (Humira®) for the treatment of adult patients with severe refractory non-infectious uveitis.

You can access the full Welsh interim policy at the link below.

Interim policy for treatment of adult patients in Wales with severe refractory non-infectious uveitis

The big question is: when is England going to catch up with Wales and Scotland (and the rest of the world)?

We were told, back in October 2015, that the published results of the VISUAL 1 and VISUAL 11  studies were required to permit the use of adalimumab to treat severe refractory non-infectious uveitis. Both sets of results are now available. We have been waiting patiently, but NHS England appears to be putting up a road block and looking for excuses for further delays.

NHS England has not yet responded to a jointly-signed letter on this subject, sent some weeks ago from ourselves (BUS), RNIB, Fight for Sight and Olivia’s Vision. There is also no sign of anyone at NHS England taking any notice of the desperate plight that a few of our members who need adalimumab treatment have had to endure for a considerable period of time. Meanwhile, their sight is continuing to deteriorate.

This is a most unsatisfactory state of affairs. BUS will continue to update you on the situation.

 

Infliximab and Humira

BUS met with NHS England in September along with a number of other eye charities and eye specialists, to try and find out what was going on and to lobby for this treatment to be available for severe refractory forms of uveitis where other treatments have failed.  We were told at this meeting that NHS England would be reviewing the situation once they had received the published results of the recent trials on children and adults.  In the meantime:-

  • Everybody already being prescribed Humira or Infliximab, will continue to have access to these drugs.
  • The current policy does NOT apply if the uveitis patient has a secondary disease eg if a child or adult is diagnosed with JRA and uveitis, they can still be prescribed Humira or Infliximab.
  • The policy only applies to uveitis patients in England.
  • The Individual Funding Request (IFR) route is still available for patients who are significantly different from other patients with uveitis. Blinding disease alone will not make a patient eligible for an IFR. In reality this means a request for individual funding will most likely be unsuccessful.
  • The clinically critically urgent (CCU) process remains open, but the criteria is usually based on having a life threatening disease, and so again, this process is unlikely to be successful for now.

We recently heard unofficially that:
The policy for the treatment of severe refractory uveitis for children has been revised and this was resubmitted last week for an in year policy development. Publication of the adult VISUAL trial data following external peer review is a key quality assurance for NHS England, and we will wait for these results to be published to revise the adult policy according to the study entry criteria and outcomes. We hope this information will be available in early 2016 and we will then be able to submit the revised adult policy as part of the NHSE in year policy development process.”

This means that for the time being,  as far as people with  Birdshot Uveitis are concerned,  there is little chance of being prescribed these drugs for their Birdshot, unless they have some other secondary condition such as rheumatoid arthritis or Crohn’s disease where the drugs are already approved.  Once the results of the VISUAL study on adults are published in a peer reviewed journal,  NHS England will be asked to reconsider.  I am afraid for the time being it is watch this space….

Campaign to overturn NHS England’s decision regarding Humira and Remicade

RNIB is running a campaign to overturn NHS England’s recent decision not to approve Humira and Remicade for the treatment of severe refractory uveitis. No doubt you know that this is a rare condition and that this decision will affect approximately 100 children and 200 adults in England per annum.

This decision will affect people with hard to treat Birdshot Uveitis who fail on the more usual treatments,  either because they do not work, stop working or cause unacceptable side effects.

RNIB is now calling on its supporters to take our e-action and send a letter to NHS England urging them to reverse their decision.  Birdshot Uveitis Society would urge all members, their families and friends to support this petition.   The e-action and template letter is simple and quick to use and can be accessed at:

http://e-activist.com/ea-action/action?ea.client.id=1670&ea.campaign.id=4107ili

Specialist commissioning process update

Birdshot Uveitis Society members based in England may be aware we have been awaiting the results of the Specialist Commissioning process which has been going on over the last year. This is the process whereby government will decide which drugs are available for different rare conditions depending on the evidence that is available which shows that the drugs are effective.

We had been led to believe that the outcomes would be announced in December.  The recent news is that the decision making process had been delayed as a result of the threat of legal action by a patient group, (nothing to do with eyes or ophthalmology, but some other rare condition), who felt that the process was unfair.

In the meantime we’d be interested to hear from any patients with Birdshot Uveitis in the UK who have been turned down for treatment with either Humira or Infliximab and whose consultants are struggling to control the inflammation in their eyes with the more usual treatments. It would be interesting to get some idea about the numbers involved and to see what can be done to help.

Please do get in touch with BUS info@birdshot.org.uk and let us know if you have been experiencing this difficulty.

T cells found in the retina and choroid of Birdshot patients

Jonas Kuiper from Holland recently contacted us to let us know that a research paper on the characterization of Immune cells in the eye of two birdshot patients has recently been published.  They successfully  identified that the infiltrated cells are predominantly T cells and that they are directed to both retina and choroid. Although this has been assumed for decades, this research provided the first evidence that T cells directed against the eye are present in the eyes of birdshot patients. http://www.ncbi.nlm.nih.gov/pubmed/24530754.

Progress with stem cell research

Birdshot Uveitis Society has noticed that there have been a lot of new development on stem cell research in the news lately which offer new hope to those whose rods and cones are losing their function.  Here are a few examples which caught our eye in January and which offer hope for Birdshotters in the future:- Continue reading