Are you taking your drugs?

Poor adherence with DMTs is costing you. Why is it a problem? #MSBlog #MSResearch

“Adherence, or compliance in old-speak, with prescribed medications is a big problem and is one of the main drivers for failure of DMTs in MS and other diseases. This study using the rate at which prescriptions are filled from a pharmacy demonstrates what a problem this is for MSers. There is unequivocable data showing that MSers who are non-adherent, or poorly adherent, to their medications do worse in terms of annualised relapses. What can we do to improve on this? This study shows that fingolimod, a tablet, helps improve adherence. However, even with fingolimod the medication possession ratio was only 0.83; i.e. 17% of doses were missed.  In fingolimod’s favour is its very long half-life, which means missing a few doses is unlikely to have a major impact on its efficacy. The only way to improve on this is to make sure we the medical profession ensure that MSers are educated and understand why the are taking DMTs and to provide them with tools to remember to take their medications. Why develop and study drugs when people don’t take them properly?”

“Any suggestions to help with adherence would be helpful.”

Epub: Agashivala et al. Compliance to fingolimod and other disease modifying treatments in multiple sclerosis patients, a retrospective cohort study.BMC Neurol. 2013 Oct 4;13(1):138.

BACKGROUND: Adherence to disease-modifying therapies (DMTs) results in the reduction of the number and severity of relapses and delays the progression of multiple sclerosis (MS). MSers with lower adherence rates experience more inpatient visits and higher MS-related medical costs. Fingolimod, the first oral DMT approved by the US Food and Drug Administration, may improve the access and compliance to MS treatment when compared to injectable DMTs.

METHODS: This retrospective cohort study used pharmacy claims from Medco Health Solutions, Inc., of MSers who initiated DMTs between October 2010 and February 2011. Initiation was defined as no prescription fills for the same DMT in the prior 12 months. Patients without a DMT prescription fill 12 months before the index date were considered naive users. Compliance was measured via proportion of days covered (PDC) and medication possession ratio (MPR) for 12 months post-index. Discontinuation was defined as a >=60-day gap of index DMT supply. Cox proportional hazard models compared time to discontinuation between cohorts.

RESULTS: Of 1,891 MSers (mean age: 45.7; female: 76.4%), 13.1% initiated fingolimod, 10.7% interferon beta-1b, 20.0% intramuscular interferon beta-1a, 18.8% subcutaneous interferon beta-1a, and 37.4% glatiramer acetate. MSers initiating fingolimod had highest average PDC and MPR in both experienced (fingolimod: mean PDC=0.83, 73.7% with PDC>=0.8; mean MPR=0.92, 90.5% with MPR>=0.8) and naive DMT users (fingolimod: mean PDC=0.80, 66.7% with PDC>=0.8; mean MPR=0.90, 87.4% with MPR>=0.8). The proportion of patients discontinuing index DMT within 12 months was significantly lower for the fingolimod cohort (naive: 31.3%; experienced: 25.7%). Adjusted results found that patients receiving self-injected DMTs discontinued significantly sooner than fingolimod users. This association was generally stronger in experienced DMT users.

CONCLUSIONS: Fingolimod initiators were more compliant, less likely to discontinue treatment, and discontinued later than patients who initiated self-injected DMT.

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.


  • I suspect that one of the factors is that you don't get better from taking the drug, it's all about reducing / slowing down… Patients i'm guessing are adherent to abx as it's only for a week and you get better. It will be interesting to see adherence levels for remyelination agents which may offer some improvements to symptoms. Adherence not an issue for me as alemtuzumab is two (5 days and the 3 days) separated by 12 months. The only adherence issue is monthly blood test for first two yeArs and annual MRI. Perhaps neuro could assess how adherent patient is likely to be – must be some simple personality tests to perfectionist or COPD (who would be super adherent).

    • If you are treated early enough with one of the high-efficacy drugs, in particular natalizumab or alemtuzumab, over a third of MSers improve in function and this is maintained for several years. The problem is accessing these drugs. In the UK you have to have highly active disease to access natalizumab and alemtuzumab has yet to assessed by NICE. The good news is that it has a relatively broad first-line license from the EMA.

    • G- you are one of the biggest supporters of drugs such as alemtuzumab which I somewhat agree with. You suggest you need to treat early to prevent further damage. Thus, I don't understand why you would advocate MSers with active disease to go on your raltegravir trial- given that it is very likely to be negative (as you have said) – are you not condemning them to greater damage?

      I do not like the false advertising you and Gold do on this website. The evidence that EBV is associated with disease activity is poor (there is no mention of the lack of replication of your EBV study) and there is no data linking HERVs. There was also a recent negative paper about HERVs that has not yet been mentioned? You and Gold seem to cherry pick data.

      Anyway, I hope there is some way that any individual who was falsely sold on your raltegravir trial can sue you for compensation should they be worse off as a result.

    • Hey..
      It´s a TRIAL, I suppose you don´t understan the concept of trials.
      They don´t know yet if it´s going to work or not so they have to test it.
      They people entering the trial are taking a big risk and I´m greatfull
      to each and every one of them. That´s how it works and if every scientist
      that failed got sued then we wouldn´t have any scientist left..
      Thatá what´s it´s all about trial and error and if you fail then get up and try again.
      I think Prif G has been very clear about what to expect and I beleive he´s doing his
      absolute best to get a cure fos us.
      regards as always
      //Swedish Sara

    • I'm waiting to see if I fit the criteria to enable me to participate in the Raltegavir trial. The delay of starting conventional DMT's is a concern of mine and one that I voiced on my visit to the research clinic. It was explained to me that if they ever feel I am in danger and would benefit from DMT's then I will be pulled off the trial. I am also free to leave the trial whenever I wish.
      I never, at any point, felt l was being coerced into participating. All questions were answered with transparency. This is my choice and one that I have thought about very seriously. I have also made it apparent to the team that if I relapse and feel I would benefit from more traditional treatment then I will call a halt to my participation in the trial. I also got the feeling that the research team would fully support my decision.

    • To: AnonymousSaturday, October 12, 2013 6:44:00 pm

      What false advertising? The trial has only ever been referred to as a hypothesis to be proved or disproved.

      I am 2 weeks into my third month on the raltegravir trial and at every stage of my recruitment into the trial (I wasn’t actually recruited as such – the moment I heard of the trial at the research day I badgered my neuro team at Barts to make sure I was tested for eligibility) and at each monthly assessment (during the 3 months baseline monitoring and during the drug part) I have been reminded that I can opt out at any time and have access to the existing DMTs.

      I resent the implication that I would be suckered into a no-hope drug trial: my reasoning is very logical. Even the most efficacious of the currently licensed DMTs do not stop MS and therefore will not prevent the progression of the disease as I age. I am not only interested in the next 15 years of my life; I’m interested in the next 40 years of my life. I therefore took an educated risk that by delaying my start on DMTs I would help our neurologists and researchers to learn more about the causes of MS and the worst case outcome would be that they would be able to draw a line through the theory and focus on other potential causes of MS. Do I think that delaying taking DMTs by a year will have a massive impact on my life over the next 15 years? Possibly. Do I think delaying taking DMTs by a year will have a massive impact in my life from years 16-40 hence? No I don’t.

      I think that much of this comes down to personality type. I am willing to take an educated risk with my health in the hope that it takes us closer to a cure and obviously I hope to benefit, but if it doesn’t actually benefit me, hopefully it will benefit the next generation of MSers. I have a VERY philosophical approach to life: yes it is precious, but absolutely nothing is guaranteed and I believe that humans in general have become far too demanding of science and un-accepting of nature and the things she unleashes, including disability and death. Not all of us will be saved from what ails us and as much as I rant against this disease and the impact it has already had on my life, I am willing to take a chance. The DMTs we have access to today are only here because previous generations of MSers have had this attitude, so it would be cruel to deny future generations a period of research.

      One of my favourite quotes is one of George Eliot’s: “What do we live for, if it is not to make life less difficult for each other?” I will not be suing anyone if the outcome of this trial is not as we all hope; I will be saying thank you to everyone involved and preparing to make my next educated decision.

      To Sara E Sunday, October 13, 2013 12:11:00 pm

      Spot on!

      To: Mitford Sunday, October 13, 2013 5:46:00 pm

      Mitford, everyone involved in the trial has constantly reminded me of my options, so please rest assured that you will not be under any pressure to stick with the trial if you decide to stop participation and start DMTs. Good luck with your journey, whichever direction you may go!

    • Now i know which paper we have not supposed to have posted due to soms form of conspiracy.
      Get real we are not a news agency and we post things when we have time

  • I am on drugs to control the symptoms so they do not make me better. I make taking them a part of my daily routine. So when I get up I automatically take my pills & and the same at night. Another important point is education For example what happens if you do not complete your course of antibiotics? The bugs reproduce into something more sinister. So education into the consequences of missing a pill and make it a part of your routine

    Dosset boxes could be an answer, the pharmacy will fill them accordingly and issue then when prescription collected – my aged mother had one and it was invaluable for the carers

  • There's an APP for that! For smartphone users there are medication APP"s that can be utilised. I am currently trialling an APP developed by the MS Society in Australia, – however it is only available on iPad at the moment. However, there are issues regarding the affordability of high end technology, being able to utilise the APP's technical requirements, and having the manual dexterity required.

    If 'forgetting' is an issue, simple low tech – a large calendar on the fridge – cross out the day number when med is taken.

  • I think part of it is better education / communication and access to support for the DMT's administered at home.

    I am a member of various MS forums and have been shocked firstly by the number of people who don't push their generalist neuros to be on DMTs in the first place, saying it's better to wait a few years before seeing if they need the drugs – a crazy point of view in my opinion as "time is brain". Then there are similar numbers who don't like the side effects and don't think the DMTs are doing anything to help so stop using them.

    Neurologists and MS nurses need to be more forthright in communicating with MSers about what to expect and then provide help in addressing self-injection issues and side effects. The unwillingness by many neurologists to deliver what might be perceived as bad news has been discussed on here already – and while both the MSer and the neurologist are involved in the communication, it must be the expert's responsibility to be the pro-active communicator.

  • Side effects have to be at or near the top of the list as the reason people don't stay on DMTs. It's one thing to take a medication with side effects when the medication will ultimately make you feel better. Many of the DMTs have significant side effects. You have to have faith they are worth it, since most don't do anything for day-to-day MS symptoms. I often see comments from others who say they are taking "vacations" from their DMTs because they have a significant event coming (vacation, wedding, etc.) and do not want the side effects to ruin it. Once you start taking breaks like this, it becomes easier to skip more often. Those breaks remind you how good you feel off the DMT.

    I'm currently on a break from my DMT due to a severe, possibly allergic, reaction. I'm torn between wanting to get on another DMT ASAP so I don't have a flare up, and being afraid of the side effects from the other choices.

    The injectable nature of the most common DMTs is no doubt a factor for many. I think the medical community doesn't realize how challenging this can be for many people. I had to overcome severe needle anxiety to do my injections, and the fear has never truly left me. Every MSer I've met has expressed their fear or hatred of injections, and I've talked to some who are too afraid to even start on medication because of it.

  • If the cost of the medication is not enough motivation for adherence go to a meeting and see progressive disease. TAKE YOUR MEDS!

  • Adherence and compliance are poor terms. Concordance is a better term – it emcompasses shared decision making and agreement between doctor and patient thus maximising uptake of prescribed medication.

  • One of the problems is there is a prevelance of nut bags in the ms community that spread the notion that drugs dont work and doctors and big pharma are out to screw them. I guess this comes from people who decline to take MS drugs early and then are upset when they start to progress and theses drugs are useless at this point. This is how ludicrous treatments such as CCSVI gain favor by MSers. But you should not feel sorry for these people. If you try to educate them about the importance of adherance thats all you can do. In the end you can't fix stupid.

    • I think patients have unrealistic expectations using DMTs. Drugs only prevent relapses and hopefully delay progression. They have to realize that even patients with low EDSS the meds need to be taken….. it's buying time.

  • The way most of these treatments go you have to choose to take or not take it every day to every week for the rest of your life. That's a lot of choices over time. What if this month I'm too depressed to hope for anything including benefit from my drug. For example. What if this week I'm on vacation and want to protect my swim suited self from injection site reactions. What if I just want to forget I'm sick. You write about quality of life but this factors into it.

    • Your theory of your quality of life isn't universal.
      1. I inject 3 times a week (with no flu-like side effects – they don't happen to everyone) because I don't want to suffer from constant relapses.
      2. It's not lifelong treatment. At some point, the MS will probably change. It may become progressive or it may just burn itself out.
      3. I have red marks. Huge ones. Get over it. You have an illness, a serious illness. Lots of people are on injections, for many conditions, diabetes, blood clotting disorders, cancer. Worrying about injection site marks is silly.
      4. If you feel depressed, then see a medic. You could well be clinically depressed. You won't know if your DMD is working. If it works, you have fewer relapses.
      5. With MS, along with Type 1 or 2 diabetes or lupus or any other incurable, but treatable disease, you just have to accept that you are ill.
      The way to do that is to find something bigger and more pleasurable and fulfilling to concentrate on. Learn a foreign language, learn to play an instrument. Whatever. If you spend you whole life obsessing about having MS and having to take injections, you'll be worse off.
      I was diagnosed at a time when all DMDs were rationed. I was scared witless that I wouldn't get treatment. It made my MS worse. I did get treatment and fast and I think it saved a lot of my motor functions. My neurologist is convinced that DMD treatment delayed progression. In fact, I have had very little progression in 13 years. You may be the same.

By Prof G



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