Polypharmacy in MS

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In this blog, our overarching goal has been to keep our readers up to date with the latest research in MS. One of the things I’ve noted in this time is that the vast wealth information out there isn’t insurmountable – you only need to select the ones that appeal to you, or are relevant to your practice. Information/’knowledge’ is probably the last bastion of monetizable commodity in the 21st century. However, with knowledge comes responsibility. So, if you’re reading the latest recommendation on our site or any other site for that matter, ask yourself: is this relevant to me?

There are many drugs and treatments out there (many of which you may have picked up from this blog), but being on all of them together may not be good for you. In a study from Rostock (Germany), they concluded that there is a great potential for drug-drug interactions (DDIs) from polypharmacy (i.e. being on at least 5 drugs at any one time).

DDIs account for 20% of adverse events, which cause between US$30 and $180 billion annually and are responsible for about 770,000 deaths“.

They found in women of childbearing age with MS, 41% had polypharmacy; the most frequent drug combinations were dietary supplements and osteoporosis drugs (Figure 1). They also found not surprisingly, polypharmacy was related to older age (average age 43 years versus 36 years), disability (average EDSS scores: 6.5 versus 2.0), a progressive disease course and other medical conditions.

Figure 1: Common drug combinations in 131 female MS patients of
childbearing age. In the graph, thick dark lines
indicate frequent combinations and large circles indicate the frequency per
drug group. The most frequent drug combination was ‘dietary supplements
and osteoporosis drugs’, which was found in 19 women

In their cohort, a mean of 4.2 drugs per patient (range: 0–15 drugs) resulted in 1033 potential DDIs (Figure 2). It is estimated that the likelihood of detecting at least one DDI in someone correlates with the number of drugs taken: ‘50% for people taking 5–9 drugs, 81% with 10–14 drugs, 92% with 15–19 drugs and 100% with at least 20 drugs’. It is also quite astonishing that the authors report that 80% of their potential drug interactions lacked evidence, so clearly more analysis is needed.

Figure 2: Potential drug interactions in women with MS. The distribution of potential DDIs according to the hazard levels is shown in a pie chart (a). Of 1033 potential DDIs (counted with repetitions) that were recognised in the patient cohort (n= 131), 3.0% were interactions of average danger. Analyses concerning polypharmacy showed that those with polypharmacy had significantly more potential DDIs of average danger than those without (b).

If you’re interested in looking at the potential drug interactions of your medications one useful site is the British National Formulary (BNF): https://bnf.nice.org.uk/interaction/.

Abstract

Ther Adv Neurol Disord. 2020 Dec 19;13:1756286420969501. doi: 10.1177/1756286420969501. eCollection 2020.

The risk of polypharmacy, comorbidities and drug-drug interactions in women of childbearing age with multiple sclerosis

Niklas Frahm Michael Hecker Silvan Elias Langhorst Pegah Mashhadiakbar Marie-Celine Haker Uwe Klaus Zettl

Background and aims: Multiple sclerosis (MS) is the most common neuroimmunological disease of the central nervous system in young adults. Despite recommended contraception, unplanned pregnancies can occur in women of childbearing age with MS. MS- and comorbidities-related multimedication in these patients represents a potential risk. We aimed to raise awareness regarding the frequency of polypharmacy and drug-drug interactions (DDIs) in female MS patients of childbearing age.

Methods: Sociodemographic, clinical and pharmaceutical data were collected through patient records, clinical investigations and structured patient interviews of 131 women with MS. The clinical decision support software MediQ was used to identify potential DDIs. A medication and DDI profile of the study population was created by statistical analysis of the recorded data.

Results: Of the 131 female MS patients, 41.2% were affected by polypharmacy (concurrent use of ⩾5 drugs). Polypharmacy was associated with higher age, higher degree of disability, chronic progressive MS disease course and comorbidities. With an average intake of 4.2 drugs per patient, a total of 1033 potential DDIs were identified. Clinically relevant DDIs were significantly more frequent in patients with polypharmacy than in patients without polypharmacy (31.5% versus 5.2%; Fisher’s exact test: p < 0.001).

Conclusion: For the first time, a comprehensive range of potential DDIs in women of childbearing age with MS is presented. Polypharmacy is associated with the occurrence of clinically relevant DDIs. This shows the need for effective and regular screening for such interactions in order to prevent avoidable adverse effects.

About the author

Neuro Doc Gnanapavan

9 comments

  • This reminds me of something else – but not entirely different: I suppose there’s no research on the succession of different DMTs? Would that possibly lead to accumulating risks/AEs inherent to each of them?

  • Thanks for this.

    The main factor for ‘polypharmacy’ in MS is that there is still no drug which stops worsening ie stops the real MS. A new RRMS patient will be prescribed a DMT to address the focal inflammation / relapses. As disability accrues they may be given additional drugs – something for spasticity, something for anxiety, something for bladder issues. As they move in to Secondary Progressive MS the add on drugs really start building up – either higher doses of drugs already being taken, or new drugs to address the mounting deficits. An MS patient may also be on drugs for hyper tension, high cholesterol, thyroid issues etc etc.

    Prof G posted something a few weeks ago about this issue – the tendency of doctors (particularly neuros) to keep prescribing drugs and the need to review which ones are really required and which ones could be dropped and replaced with exercise or dietary changes etc.

    As noted at the start, the best solution would be a drug which stops the real MS / smouldering MS and a drug which encourages some repair. It’s the progressive nature of MS / worsening disability which leads to those with advanced MS taking a huge amount of different drugs to (moderately) tackle the huge amount of grim symptoms.

    • I hear what you’re saying, the early treatment strategy with highly active medications is currently the best strategy available in MS. When used effectively – in my opinion works, and there is little need for additional symptomatic treatments. The major problem that neurologists face is that when patients state that a symptom is not bearable you end up either prescribing or escalating existing treatments. I agree this isn’t a good strategy. Something, I’ve discussed with my managers in my MS clinic is putting in MDT slots – 45 min each (gold dust in the current NHS!); and one of the goals of this clinic is to tackle this polypharmacy…

  • Guess that it’s not so surprising to have 80% lack of evidence especially when this study includes dietary supplements. The lack of relevant and reliable information on them is bad enough , add the lack of regulation and you could be swallowing a pill of talcum powder! You’d think this would stop me from taking them but it doesn’t because I couldn’t bear the thought of if only I’d taken them I’d be better off with regards my MS – feels like being caught between a rock and a hard place.

    • 🙂 Just to make you pause a bit more. In 1994 Bill Clinton passed the Dietary Supplement Health and Education Act (DSHEA). Until then in the US dietary supplements were scrutinized as much as foods and drugs by the FDA. The bottom line is that supplements in the US since this Act do not require FDA approval before they’re marketed. Which, leaves the US in a very bizarre scenario where they can query ingredients on supplements pre-1994 but not after!

  • I would check what happens with age matched people. I mean some drugs classes are very common and sombre of them relate well. If people have relapses they will get corticosteroids that cause bone loss so people will take dietary supplement (vD?) and osteoporosis drug and likely analgesics.
    Also people on DMTs are advised on using contraceptives so it’s normal that some of the women will select contraceptive drugs.
    On top of that I would say that gastrointestinal drugs (if this include antacids) are prescribed for quite common problems such as reflux and to protect the stomach from analgesics (I am not so sure this helps with many other drugs than FANS). So, at this point we have already covered 6 different class of drugs, those with the strongest use and association. I am not saying that this is good but this can be expected.

    Then I agree with most of the statements above if MS is early and effectively treated people will not need to take additional risks. I hope the trials pin early highly active vs escalation therapy put this discussion to bed once and for all.

    On supplements there is lower control and less studies carried out. Some scientists and neuros could run trials on their own for some of this drugs but this is a big game for a possible minimal benefit and only few will do this also considering that recruiting for trials could not be so easy.

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