Drug induced lymphopenia and evidence of infection


I will just put this up without to much discussion but it suggests that the lymphopenia associated with dimethyl fumarate and fingolimod are not really linked to noticably higher infection rates in the real world setting. This view has been repeated for many other agents that blood cell numbers do not appear to correlate with disease activity. Now it may be if you drill down on specific subsets you may find something, but remember only about 2% of your lymphocytes are found in the blood at any one time. They do their dirty work in the lymph glands and spleen for example and do into tissues to finish off infections.

Fingolimod and Dimethyl-Fumarate-Derived Lymphopenia is not Associated with Short-Term Treatment Response and Risk of Infections in a Real-Life MS Population. Boffa G, Bruschi N, Cellerino M, Lapucci C, Novi G, Sbragia E, Capello E, Uccelli A, Inglese M. CNS Drugs. 2020 Mar 19. doi: 10.1007/s40263-020-00714-8. [Epub ahead of print]

BACKGROUND:The association between treatment-related lymphopenia in multiple sclerosis, drug efficacy and the risk of infections is not yet fully understood.

OBJECTIVE: The objective of this study was to assess whether lymphopenia is associated with short-term treatment response and infection rate in a real-life multiple sclerosis population treated with fingolimod and dimethyl-fumarate. We assessed the associations between baseline absolute lymphocyte count and the lymphocyte mean percentage decrease at 6 and 12 months with treatment response and the occurrence of adverse events over 12 months in the entire cohort of patients and in the two treatment groups separately.

METHODS: This is a retrospective observational real-world study of patients with multiple sclerosis treated with fingolimod and dimethyl-fumarate at the MS Center of the University of Genoa between 2011 and 2018. Patients with at least 12 months of follow-up were eligible if [1] they had an Expanded Disability Status Scale assessment at baseline and 12 months after treatment onset, [2] they had undergone brain magnetic resonance imaging at baseline and after 12 months, and [3] absolute lymphocyte counts were available at baseline, 6 and 12 months. Patients shifting from dimethyl-fumarate to fingolimod or vice versa were excluded from the analysis.

RESULTS: In total, 137 and 75 patients treated with fingolimod and dimethyl-fumarate, respectively, were included in the analysis. At 12 months, fingolimod-treated patients were more likely to experience grade II and grade III lymphopenia compared with dimethyl-fumarate patients (p < 0.001, χ2 = 94) and had a higher lymphocyte mean percentage decrease (p < 0.001, U = 540). A higher number of previous therapies and a lower baseline absolute lymphocyte count were predictors of lymphopenia at 6 months (p = 0.047, odds ratio = 1.60 and p = 0.014, odds ratio = 1.1) and 12 months (p = 0.003, odds ratio = 1.97 and p = 0.023, odds ratio = 1.1). In fingolimod-treated patients only, female sex and a higher Expanded Disability Status Scale score were predictors of lymphopenia at 12 months (p = 0.006, odds ratio = 7.58 and p = 0.03, odds ratio = 1.56). Neither absolute lymphocyte count at 6 and 12 months nor the mean percentage decrease at 6 and 12 months predicted No Evidence of Disease Activity (NEDA-3) status at 1 year, the occurrence of relapses, disease activity on MRI or disability progression.

CONCLUSIONS: Our findings suggest that peripheral blood lymphocyte changes are not associated with short-term treatment response and with the rate of infections during fingolimod and dimethyl-fumarate treatment in real-world patients. Higher treatment exposure and a lower baseline absolute lymphocyte count are risk factors for lymphopenia development during fingolimod and dimethyl-fumarate therapy.

I don’t have access to the full paper

COI Multiple none rlevant

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  • I’ve been on Tec for 5 years and I find the difference to before being on Tec that I still get colds / flu etc but I experience less of the “superficial” symptoms but feel more of the underlying “not feeling well” and for much longer. I also contracted shingles last year which went on for 6 months and was really painful. Before MS & Tec I had a strong display of symptoms of colds etc. So, from my experience I believe my initial immune response is suppressed and it takes my immune system longer to fight illnesses. This is what worries me about covid19 as I have read that the initial immune response is important in recovering before the virus gets to stage 2 & pneumonia etc. My lymphocytes went down to 0.5 last year and seem to vary between .5 and .8. For these reasons I have decided to reduce my tec to 1 pill of 240mg per day in the hope that my lymphocytes recover enough to put up a decent initial immune response but I also retain some relapse protection from the tec.

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