MS Treatments May Lower Levels of Immune White Blood Cells

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Multiple sclerosis patients are at risk of developing lymphopenia, or abnormally low levels of immune defense white blood cells, called lymphocytes, according to a study that investigated lymphocyte counts in people with relapsing MS both before and after the start of treatment. The study, “Lymphopenia in treatment-naive relapsing multiple sclerosis,” was published in the journal Neurology.

Various therapies are today available to help treat relapsing MS, with the primary goal of regaining function after an attack, preventing new attacks, and, particularly, preventing disability progression. However, as with many other medical treatments, those designed for MS management can cause adverse effects. Some studies have suggested that some medications cause lymphopenia, which is risky in MS because lymphocytes are essential to protecting the body from infection.

Researchers investigated the prevalence of lymphopenia in pretreatment MS patients. The team collected and analyzed data, acquired between 2012 and 2014, from the Southampton regional MS service in the U.K. Patients were classified by  age, sex, comorbidities, category of relapsing MS, age at disease symptom onset, number of affected functional systems, dates related to pre- and post-treatment lymphocyte counts, relapse date and severity, and date of starting treatment. For control reasons, lymphocyte data were also taken from healthy individuals, matched by age and sex, treated at the same hospital for cosmetic procedures.

Using blood test data, researchers identified 764 patients. Of  these, 466 had baseline and 247 had post-treatment blood test results available, with an average of four tests per year.

Researchers detected lymphopenia in 48 patients (10%). When they looked at causes, researchers found the administration of steroids in the month before lymphopenia to be the reason in three distinct cases.

Further analysis revealed no association between pre-treatment lymphocyte count and patient criteria that included age, sex, MS category, autoimmune comorbidities,  disease duration, time since the last relapse, and last relapse severity. A comparison between observed lymphopenia in the treatment-naive MS population and matched controls also showed no statistical difference in the prevalence of lymphopenia.

After treatment with MS drugs, namely Avonex/Rebif (interferon beta) or Copaxone (glatiramer acetate), the prevalence of lymphopenia rose to 28%, with 26% of these patients having grade 1 lymphopenia and 2% with grade 2 (the higher the grade of lymphopenia, the lower the levels of lymphocytes). Results also showed that patients’ immune white blood cell lymphocyte counts declined after starting interferon beta therapy, but were not affected by glatiramer acetate therapy. Gilenya (fingolimod) was found to cause lymphopenia in all patients, and Tysabri (natalizumab) also reduced lymphocyte count compared to baseline.

“In our treatment-naive relapsing MS population, we found lymphopenia in 10%. However, this was not different from a well-matched healthy control population. Moreover, lymphopenia was not associated with relapsing activity. Hence, the lymphopenia in patients with MS is unlikely to be related to autoimmunity. A more likely explanation is stress-induced lymphopenia in both cohorts, through cortisol or Epstein-Barr activation,” the authors concluded.

“We found that pretreatment lymphopenia predicts posttreatment lymphopenia; this is useful since it identifies at-risk patients needing frequent monitoring,” they added, and advised, “Because of this study’s retrospective nature, lymphocyte subsets were not available, and these are important. Further work is needed to determine whether lymphocyte subsets during lymphopenia differ in patients with MS vs controls.”

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Malika Ammam received her MS degree from the University of Pierre et Marie CURIE in July 2002 and her PhD from the University of Paris Sud XI, France in September 2005. From 2006 to 2007, she worked as a research fellow at the University of Kansas in collaboration with Pinnacle Technology Inc. (USA). From 2007 to 2010, she was a research associate at KU Leuven, Belgium. From 2010 to 2012, she worked at the University of Ontario Institute of Technology in collaboration with Alcohol Countermeasure Systems Corporation, Canada. She held a prestigious Rosalind Franklin fellowship and resigned in 2015. Now, she is a freelancer.
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  1. Tricia says:

    They don’t mention Tecfidera. My neurologist had me stop treatment 9 months ago after several years of very low lymphocyte counts which was considered normal until the report of several PML related deaths from Tecfidera. It was originally assumed my levels would return after 4-6 weeks, then 3-4 months, now Biogen website says they are finding that levels don’t return to pre-medication levels. However, my levels were mid-range normal always before treatment with Tecfidera; post-Tecfidera they start to return to almost lowest “normal” level and then bottom back out again. It appears to be a recurring problem in that I monitor my diet to include things that should be good for your immune system and when it almost gets back to bottom rung normal range it bottoms out again. I have not been able to get back to a “normal” range for my lymphocyte counts. Not returning to normal (ongoing lymphopenia) is different than not returning to pre-treatment levels. Anyone else seeing this?

    • John says:

      I was on Tecfidera and still am on the starter dose. I never had low counts after 9 yrs on Copaxone. My total count is still around 400 after 2 months on a lower dose. I was on the full dose for only 3 months when they tested me. So what did they switch you to? My dr. says only 2-3% are supposed to run into this problem but his patients are running over 20% getting lymphopenia.

      • Tricia says:

        I haven’t been able to start anything else yet since my lymphocyte count is still very low. You mentioned being on the full dose but still being on the starter dose. Are you saying you did the starter dose of Tecfidera, went to the full dose, and then switched back to the lower dose because your lymphocyte count got real low? If so – make sure your blood work is checked frequently. If your counts got that low that quick, this might not be the right drug for you. I saw the doctor earlier this week and was told they are starting to see this pop up with some people that there counts don’t return after the newer MS medications like Tecfidera and some of the others.

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