Saturday, 29 October 2016

#PoliticalSpeak & #OffLabel: stand-up and shout

Why are neurologist's so reluctant to prescribe off-label DMTs? #PoliticalSpeak #OffLabel #MSBlog

It is wonderful to see some momentum behind the off-label use of DMTs for treating MS. Since the Swedish experience with rituximab was published a few weeks ago the position paper on reducing the cost of MS treatments below came to my attention with an accompanying blog post, 'Stand-up for Rituximab'. 


On this blog we have been actively promoting off-label prescribing for over two year. The motivation for doing started on my sabbatical in 2014 when I visited South Africa and saw first-hand how pwMS were not being treated with DMTs because of their high price. My position on this only got stronger when I visited other resource poor countries, in particular India. We have now generated a list of 9 off-label treatments; 5 of which are on the WHO list of essential medicines. The latter is important in that this ensures they are available in almost all resource poor countries. 
  1. Azathioprine*
  2. Cladribine
  3. Cyclophosphamide*
  4. Fludarabine*
  5. Leflunomide
  6. Methotrexate*
  7. Mitoxantrone
  8. Rituximab*
  9. HSCT/BMT 

Please note that Rituximab is not a cheap drug. It will come off patent soon and hopefully the biosimilars will reduce its price. However, as rituximab is a biological, biosimilars will only have a modest impact on its price. Then there is brand loyalty. In India they already have a rituximab bio-similar, Reditux. Despite it costing a third of the price of the innovator compound, MabThera, its is not as commonly used as you would think. When I visited NIMHANS, the large neurology centre in Bangalore, I was told that Reditux was not as good as MabThera. However, when I look at the B-cell depletion data, and B-cell re-population kinetics, of Reditux there was no indication that it was inferior to MabThera. What we are seeing play out here is the power of the brand. Indian neurologists trust and feel more comfortable prescribing something they know. They simply believe that Reditux is inferior and they want the best for their patients. Please note they were not using rituximab to treat MS at NIMHANS, but were using it for other neurological conditions. 

The MS community needs to understand that off-label prescribing is unlikely to take-off without political support. The latter is not going to happen any time soon, trust me we have tried to get British politicians behind our campaign. Politicians have to take a macro-economic view of the world and tend to have little interest in single-issue diseases. It is clear that our politicians have struck a deal with Pharma and have put in place rafts of legislation to protect Pharma's intellectual property and business models on the condition that Pharma continue to spend money on R&D, create and support local jobs and more importantly generate large sums of money for the tax coffers and pension funds. However, Pharma must not assume that their cosy and rather 'special' relationship with government is going to stay the same if they don't deliver on their obligations. A few bad apples have been giving Pharma a very bad name and it is up to Pharma to clean-up their act. For example, Gilead's share-buy back programme to boost their share-price, and maximise staff bonuses and short-term shareholder value, over spending their profits on R&D is simply outrageous. This is why Gilead are in the cross-wires of US politicians; they have renegaded on the deal. 

We all agree that at the moment Pharma are the only show in town, but they need to act responsibly and not abuse their privileged position. If they don't society will turn against them. The high-cost of MS drugs is one of many factors that is contributing to their bad public image. This is something that Pharma can do something about. I sincerely hope that Roche assesses the situation carefully, with a big and responsible worldview, and that they make ocrelizumab affordable. Ocrelizumab does have advantages over rituximab, but if ocrelizumab is too expensive the community will find ways to disrupt the market and use rituximab. 

At our Barts-MS strategy day we decided to hand-over the baton for our #OffLabel campaign to the MS International Federation. We only have so much time in a day and we also failed to get our health policy unit at Barts and The London to engage with this campaign. We need people who understand policy and have the necessary resources to run a political campaign. One of the priorities of the MSIF are increasing drug access for pwMS living in resource-poor environments and off-label prescribing is one way to achieve this. We will continue to help and support the #OffLabel campaign, for example by posting about it on this blog, but it will not be a major priority of our group this year. Please note we will continue to make available our protocols for off-label prescribing. 


Annette M. Langer-Gould. Stand up for Rituximab. NEUROLOGY E D I T O R' S B L O G, O C T O B E R 1, 2 0 1 6.

Excerpts:

...... The unaffordability of MS medications is driven by the outrageous prices that are in no way tied to the benefits these medications provide....


...... The experiences they share include a few simple strategies to lower costs without diminishing quality of care. The one with the most impact is the use of rituximab.... 

...... The biggest barriers to implementing rituximab use are: 1) most insurance carriers deny coverage because it is not FDA approved for MS; 2) neurologists are afraid of legal action if they prescribe a non-FDA approved product and 3) the drug companies are incredibly good at marketing their products with glossy ads to promote brand bonding, enticing many prominent neurologists with speaker fees, dinners, first-authorship on New England Journal articles for studies they didn’t design, conduct, analyze and so on....... 

...... Biogen and Roche are already busy creating false distinctions between ocrelizumab and rituximab as they did for Lucentis and Avastin and frightening neurologists into believing they would be harming their patients or at risk of litigation if they use rituximab......

...... Off-label prescribing is what neurologists do all the time, the only legal risk is if ocrelizumab had been proven to be superior or safer than rituximab, data that do not exist and a study Roche and Biogen would be afraid to conduct......

....... The Swedish and Kaiser Permanente neurologists negotiated with their medical centers to allow the use of rituximab in their highly active patients when natalizumab was not an option. Use of rituximab has increased dramatically in Sweden and Kaiser Permanente as the highly favorable efficacy/safety profile and high patient satisfaction becomes clearer......

....... Pharma tried to pressure the Swedish government to halt this use of rituximab, which was met by outrage from their neurologists. Swedish health care authorities reviewed the extensive use of rituximab in MS and deemed it scientifically sound and legal.....

....... I urge all neurologists to stand up for their patients as the Swedish neurologists have done and help your patients get access to rituximab.......

Kister & Corboy. Reducing costs while enhancing quality of care in MS. Neurology October 11, 2016 vol. 87 no. 15 1617-1622

The rapid escalation in prices of disease-modifying therapies (DMTs) for multiple sclerosis (MS) over the past decade has resulted in a dramatic overall increase in the costs of MS-related care. In this article, we outline various approaches whereby neurologists can contribute to responsible cost containment while maintaining, and even enhancing, the quality of MS care. The premise of the article is that clinicians are uniquely positioned to introduce innovative management strategies that are both medically sound and cost-efficient. We describe our “top 5” recommendations, including strategies for customizing relapse treatment; developing alternative dosing schedules for Food and Drug Administration–approved MS DMTs; using off-label therapies for relapse suppression; and limiting the use of DMTs to those who clearly fulfill diagnostic criteria, and who might benefit from continued use over time. These suggestions are well-grounded in the literature and our personal experience, but are not always supported with rigorous Class I evidence as yet. We advocate for neurologists to take a greater role in shaping clinical research agendas and helping to establish cost-effective approaches on a firm empiric basis.

Some other blog posts of interest on off-label prescribing

Oct 18, 2014 ... "In response to some of the comments yesterday I have to stand up for people living with MS in South Africa and defend their right to treatment.
4 days ago ... The study below summarises the off-label experience of using rituximab to treat both relapsing and progressive forms of MS in Sweden.
Sep 5, 2016 ... HSCT-BMT had been added to our essential unlicensed treatments list # PoliticalSpeak #MSBlog #OffLabel. An important issue we, and others, ...
Jun 18, 2015 ... Therefore we are in a Catch-22 situation at present with regard to the use ofofflabel rituximab for treating MS in the NHS. This is great pity as it ...
Oct 18, 2016 ... #ClinicSpeak & #OffLabel: alemtuzumab between a rock and a hard place ... that 3rd, and subsequent courses, of alemtuzumab are off-label?
Jan 14, 2016 ... BartsMS Off-label Cladribine use Information Sheet. For those Health Care professionals and People with MS who may be interested. We have ...
Apr 15, 2015 ... "After last week's post on off-label prescribing, I contacted our health policy unit about formally addressing this issue in the UK with the aim of ...
Dec 30, 2015 ... "A part of the solution we have been promoting the use of off-label, cheaper, alternative DMTs to treat MS. The following is our Barts-MS ...
Dec 16, 2014 ... Off-label rituximab as an add-on therapy in patients with breakthrough disease on first-line agents was associated with an 88% reduction when ...
Apr 15, 2016 ... The use of off-label drugs to treat MS in resource-rich environments remains a hot potato. Despite been given the green-light to do so by our ...
Jul 26, 2016 ... "Let's hope the rituximab data is good enough for NHS England to adopt off-label prescribing in MS; at present they won't. At last, we will know ...
Jan 27, 2016 ... The issues in the disease areas discussed in this piece dovetail to some extent with our off-label prescribing initiative and the Barts-MS ...

CoI: multiple

5 comments:

  1. Do you think we are too 'under the thumb' of pharma?

    Could we make more intelligent choices? What would you do for co-morbid MS and rheumatoid arthritis?

    ReplyDelete
    Replies
    1. Re: "Do you think we are too 'under the thumb' of pharma?"

      Possibly, but we have created the beast. We can't develop drugs without them. It is too expensive and risky to do this under models. It is not them or us. We need to view it as a partnership.

      Delete
  2. Are you dumping your cladribine programme?

    ReplyDelete
    Replies
    1. Re: "Are you dumping your cladribine programme?"

      No there is a lot of activity on this front; DrK is leading on it. We want to do comparative efficacy trials in resource-poor settings and we want to do a trial of cladribine in more advanced MS including pwMS in wheelchairs.

      Delete

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