Monday, 9 April 2018

With Current Non-selective DMT there is an infection risk

Treatments that block MS activity, can lead to infection


Wijnands JMA, Zhu F, Kingwell E, Fisk JD, Evans C, Marrie RA, Zhao Y, Tremlett H. Disease-modifying drugs for multiple sclerosis and infection risk: a cohort study. J Neurol Neurosurg Psychiatry. 2018. pii: jnnp-2017-317493.

OBJECTIVE: Little is known about disease-modifying treatments (DMTs) for multiple sclerosis (MS) and infection risk in clinical practice. We examined the association between DMTs and infection-related medical encounters.
METHODS:Using population-based administrative data from British Columbia, Canada, we identified MS cases and followed them from their first demyelinating event (1996-2013) until emigration, death or study end (December 2013). Associations between DMT exposure (by DMT generation or class) and infection-related physician or hospital claims were assessed using recurrent time-to-events models, adjusted for age, sex, socioeconomic status, index year and comorbidity count. 

RESULTS: Of 6793 MS cases, followed for 8.5 years (mean), 1716 (25.3%) were DMT exposed. Relative to no DMT, exposure to any first-generation DMT (beta-interferon or glatiramer acetate) was not associated with infection-related physician claims (aHR: 0.96; 95% CI 0.89 to 1.02). Exposure to any second-generation DMT (oral DMT or natalizumab) was associated with an increased hazard of an infection-related physician claim (aHR: 1.47; 95% CI 1.16 to 1.85); when assessed individually, the association was significant for natalizumab (aHR: 1.59; 95% CI 1.19 to 2.11) but not the oral DMTs (aHR: 1.17; 95% CI 0.88 to 1.56). While no DMTs were associated with infection-related hospital claims, these hospitalisations were also uncommon.
CONCLUSION: Exposure to first-generation DMTs was not associated with an altered infection risk. However, exposure to the second-generation DMTs was, with natalizumab associated with a 59% increased risk of an infection-related physician claim. Continued pharmacovigilance is warranted, including an investigation of the DMT-associated infection burden on patient outcomes.

You can't have you cake and eat it. This study looks at infection risk and use of a DMT and it says the weakly active DMT are not associated with the risk of infection,. In contrast the highly active DMT were associated with infections. 

The second line orals are not associated with infections but we they appear to be less active than natalizumab. If you are using an immunological sledge-hammer to crack a nut, you are targeting the immune system and putting holes in it, then if it is effective at doing that, it will be effective at blocking the  immune system that controls infection.

6 comments:

  1. The interesting thing I noticed, that years after alemz treatment I started to have less overall infections like flu or cold, than before. Some others I asked told me the same.
    Wonder how this stands against low CD4/CD8 cell counts found after after the treatment

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    1. Interesting.
      In terms of T cells the memory T cells repopulate preferentially and also CD8 counts repopulate alot quicker than CD4

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    2. The cell counts 2 years after. In Russian unfortunately but I think can be understood in terms of CD# thing, reference is the last column
      https://i.imgur.com/Sqkfz8V.png
      As I understand still deficient in both domains

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    3. Since being diagnosed with MS I have had hardly any colds in 12 years something which other Msersalso claim

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    4. As far as I can understand and I certainly might be wrong, all this immune thing is so mysterious, that no model of it exist from which you can derive any predictions like you got such and such cells in such and such numbers and it implies you'll have such and such risk for this and that disease
      Hope Prof Mouse can correct me

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  2. Would that imply that cancer risk is higher with second line treatment (natalizumab in that case)?

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