Protecting yourself from the influence of DMF….Time for another pie:-)

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Yes this is a not so serious post, on a serious matter.

Dimethyl fumarate can cause white blood cells to drop and this is a risk factor. This study is a data mining study and reports on factors that promote disappearence of white blood cells…..one is being old and the other is being too thin. They also looked at sex and white blood cell levels. In most cases these are not things you can do anything about, but there was no suggestion that gender re-assignment was going to be of value. We can’t do too much about age…and as you age your immune system ages and is less go at repairing…so the only thing you can do something about is to get fat….So that’s your excuse to chow-down and have another pie. However, surely this is a NSS moment and says where are we in terms of personalised medicine. Cladribine is one of the few treatments that are dosed according to weight. If you are large with a BMI of 40 and you compare yourself to someone with a BMI of 20. In the situation above the heavy person is getting about half the amount of drugs compared to the skinny person because their is fixed dosing so there is a reduced chance of depleting your white blood cells too much. Most trials will study a higher dose that the actual marketed dose so that even if you are getting more drug it is still relatively safe.

Ocrelizumab dosing suggests more benefit in the smaller people, so a trial is being done using a larger dose, here better dosing levels/depletion may mean more efficacy.

Dosing to size is the basis for most animal experiments, I suspect that for most drugs there is fixed dosing because it is easier to administer and less chance of a mistake. Than tailoring doses to size.

Ravn J, Jensen HB, Kant M, Andersen PB, Góra MK, Sejbaek T. Risk factors for development of lymphopenia in dimethyl fumarate-treated patients with multiple sclerosis. Mult Scler Relat Disord. 2022;67:104081. 

Background: Dimethyl fumarate (DMF, Tecfidera®) is a first-line disease-modifying therapy for relapsing-remitting multiple sclerosis. Lymphopenia is a frequent reason for discontinuation in fumarate-treated patients. Management strategies to minimize risk of lymphopenia are warranted.

Objective: The aims of this study were to investigate the correlation of body mass index (BMI), baseline absolute lymphocyte count (ALC), age and sex with risk of DMF-induced lymphopenia in MS patients.

Methods: The study was a retrospective cohort study of 452 MS patients who had been prescribed DMF at six clinics in two Danish regions between May 2014 and September 2017. Data on lymphocyte counts, BMI, age, sex, and reason for discontinuation of DMF were collected through the Danish Multiple Sclerosis Registry, with follow- up to two years after treatment start.

Results: 28.5% of patients had lymphopenia grade II or higher at some time in the first two years of DMF treatment. Increased risk of lymphopenia was observed in patients with baseline ALC of 1.00-1.49×109 cells/L (odds ratio, OR 5.48, p<0.0001) and 1.50-1.99×109 cells/L (OR 2.08, p = 0.0009). Reduced risk of lymphopenia was observed in patients with ALC of 2.00-2.49×109 cells/L (OR 0.51, p< 0.01) and ≥ 2.50×109 cells/L (0.12, p<0.0001). Patients aged ≥ 56 years had an increased risk of lymphopenia (OR 3.58, p<0.001), and patients with BMI ≥ 30 kg/m2 had a decreased risk of lymphopenia (OR 0.53, p value = 0.03).

Conclusion: Low baseline ALC and older age were risk factors for DMF-induced lymphopenia, while BMI ≥ 30 kg/m2 and high baseline ALC were protective factors for developing lymphopenia in MS patients treated with DMF.

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MouseDoctor

3 comments

  • As BMI takes account of height as well as weight, should dosage be based on weight or BMI?
    BMI would indicate physiological such as proportion of fat whereas weight indicates size so more drugs required to achieve same concentration.

    Fine to make jokes, but we should try and think about the scientific issues.

    I am an old man (but only 5 years diagnosed) on Tecfidera with low lymphocytes and an average BMI. My wife did not approve my application for an extra slice of her excellent Irish apple pie on your synopsis.

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