Drug switching: treat-2-target NEDA

Are neurologist being ageist when it comes to adopting new treatment paradigms? #MSBlog #MSResearch 

“Although this study below is retrospective it does describe the behaviour of practicing neurologists when it comes to prescribing disease-modifying therapies (DMTs) in clinical practice. Treat-2-target of no evidence of disease activity (T2T-NEDA) is beginning to be adopted in healthcare environments were there is no restriction on prescribing, this is mainly in the U.S. In Europe, and particularly in the UK, we have national guidelines that prevent us adopting T2T-NEDA; in other words MSers have to really fail their current DMT with disabling clinical attacks before we can escalate their therapy. In other words, those of us doing routine monitoring MRIs on an annual basis, are being forced to watch smoldering MS shredding the brain. What is interesting about this study below is that it is US based and it clearly shows early adoption of T2T-NEDA, even though this study involves an epoch in which T2T-NEDA was not be widely discussed. It is also interesting that age affected decision making; younger MSers were more likely to get switched. Why? May be the younger MSers were more educated and asked questions more frequently; in other words they were actively involved in their clinical decision making about their treatment compared to older MSers. May be prescribing neurologists thought younger MSers had more to lose. Maybe older MSers were more reluctant to switch; habits die hard. It would be interesting to follow-up this study with a qualitative in-depth study to explore the reasons for the behaviors highlighted in this study.”
“You may be interested to hear that the second Cleveland Clinic NEDA meeting is happening this week in Las Vegas. I wonder if these softer social issues concerning prescribing behaviour will be discussed?”

Epub: Teter et al. Characteristics influencing therapy switch behavior after suboptimal response to first-line treatment in patients with multiple sclerosis.Mult Scler. 2013.

BACKGROUND: Factors driving disease-modifying therapy (DMT) switch behavior are not well understood.

OBJECTIVE: The objective of this paper is to identify MSer characteristics and clinical events predictive of therapy switching in MSers with suboptimal response to DMT.

METHODS: This retrospective study analyzed MSers with relapsing-remitting multiple sclerosis (MS) and a suboptimal response to initial therapy with either interferon β or glatiramer acetate. Suboptimal responders were defined as MSers  with ≥1 MS event (clinical relapse, worsening disability, or MRI worsening) while on DMT. Switchers were defined as those who changed DMT within six to 12 months after the MS event.

RESULTS: Of 606 suboptimal responders, 214 (35.3%) switched therapy. Switchers were younger at symptom onset (p = 0.012), MS diagnosis (p = 0.004), DMT initiation (p < 0.001), and first MS event (p = 0.011) compared with nonswitchers. Compared with one relapse alone, MRI worsening alone most strongly predicted switch behavior (odds ratio 6.3; 95% CI, 3.1-12.9; p < 0.001), followed by ≥2 relapses (2.8; 95% CI, 1.1-7.3; p = 0.040), EDSS plus MRI worsening (2.5; 95% CI, 1.1-5.9; p = 0.031) and EDSS worsening alone (2.2; 95% CI, 1.2-4.1; p = 0.009).

CONCLUSIONS: Younger MSers with disease activity, especially MRI changes, are more likely to have their therapy switched sooner than MSers who are older at the time of MS diagnosis and DMT initiation.

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.


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  • Prof G,

    Will you be attending the NEDA meeting in Cleveland?

    Why do MS patients get such a poor deal? Surely, the aim of any treatment (for any disease) is to shut down the disease (all of the disease). I can't imagine any oncologist telling their patient that they will first try a modestly effective treatment first i.e. might kill 30% of cancer cells – the patient wants all the cancer cells irradicated.

    Is it just about money i.e. it costs a lot more to really have an impact on this disease? Why do neurologists / MSologists let this situation persist? Surely you are the professionals / experts and should know your patients / put their best interests at the forefront. If I had highly active MS diagnosed and came to you, what actually prevents you from prescribing Tysabri (if it's obvious that starting interferon / copaxone will have little effect). Surely your professional judgment must mean something! Perhaps it's the neuros that are the real issue i.e. they are just prescribing as instructed by a Committee. On this basis, the job is almost a technical one i.e (i) patients arrives with symptoms…. (ii) send for MRI….(iii) read out the results of MRI to patient (dx RRMS)… (iv) prescribe Copaxone as per manual. I could do that and I have no medical training. Surely step (iv) should be.. discuss treatments options with patient / share your experience of treating other patients / discuss risks and benefits…prescribe (if patient happy) most effective treatment available. Sad state of affairs when people with such a horrible disease aren't offered the best available treatment.

  • I agree entirely with this. The problem needs to be separated into two distinct issues however.

    Firstly, is the FDA/EMA/neuro issue – i.e. leaving aside money, can I have drug x for my condition. If the drug is proven effective then (a) the FDA/EMA should licence front line and (b) neuros should give the patient the information as to efficacy versus side effects and (c) the patient should then make an informed choice. I can scarely imagine ANY drug for MS that shouldn't be given a first line authorisation, provided the patient is aware of the risks. MS can be (isn't always, but definitely is often) a terrible condition and an informed patient should be able to take any risk they want in trying to minimise/remove it's impact from their lives. If a highly efficacious drug, assume close to a cure in terms of stopping progressing, came with, say, a 1 in 10 chance of death – there would be patients who would be willing to take those odds and they should be allowed to, in my view.

    The second issue is more challenging and that is the funding. Whereas I feel the drug choice should be almost complete for patients, I'm not so sure that I can bring myself to say that the NHS should be required to fund any drug for any patient, regardless of the cost. To do so is unrealistic. It might be awful but it's just a consequence of the fact that, in the UK, free, 'rollls royce' healthcare is not sustainable for all. It's the same with drugs for cancer and many other terrible conditions. The difference with the cancer drugs etc is if you are lucky enough to be able to afford them, you don't have patronising doctors/regulators telling you you can't have them anyway. I do believe NICE have a difficult job to weigh up the cost versus efficacy of different options moving forwards. Generic IFN Beta will become available from next year and will be exceptionally cheap. Is aubagio, for example, significantly more effective – or is just more palatable for the patient? (Although, interestingly, I believe aubagio will be made available to MSers on the NHS). How far should NICE look? Is the cost of Alemtuzumab, say, justified through the societal savings by preventing MSers from becoming disabled, losing their jobs etc. I'd say it absolutely was. Alemtuzumab is expensive (based on German pricing – around £60k), but potentially that is it, for life – on that basis, long-term it's probably even cheaper in a sense than IFN or GA. What about something like BG12? That would cost, c. £30p.a. based on US pricing (we'll probably be cheaper). Assuming a newly diagnosed MSer lives for 35 years say, post-diagnosis, that's £1,050,000. Suddenly, I think there's a genuine issue to be considered.

    What I definitely think is that NICE and neuros should, together, have NEDA as the treatment goal and then look at efficacy on that basis. To allow a diagnosed MSer to have to suffer brain damage before even allowing funded treatment is unconscionable. It wouldn't be tolerated for any other disease affecting any other organ of the body. It's absolutely no different to telling someone with lung disease – once one of your lungs stops working, we'll give you some treatment. It's scandalous.

  • Anecdotally, I see older MSers in my community stay with ineffective treatments because they are with the older neurologist in town. I occasionally hear them say that he is the most experienced at MS, and that might be true. But when I talk to them, they don't know about the most current treatments, and they may go years without an MRI. My neurologist, on the other hand, graduated just a couple years ago and often starts his most aggressive cases on Tysabri (I'm in the U.S., they can do that here.)

By Prof G



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