ACTRIMS2021:Lymphocyte recovey after DMF

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Some people chose dimethyl fumarate and this can cause significant drop in lymphocyte numbers and so this causes a headache for the neuro about switching you to other treatments. If you stop fingolimod or natalizumab disease can rush back (rebound), however with depleted cells they repopulate at a slow rate and so are unlikely to appear all at once and so rebound is less likely and relapses may appear and occurred in some people but are less likely to occur at once. Lymphocytes generally recovered within 2 months

K. Balashov1, K. Giles2, K. Pandey3, J. Windsheimer4, J. Lyons5, R. Rajbhandari5, J. Messer5, N. Everage5;


Background: Delayed-release dimethyl fumarate (DMF) demonstrated a favorable benefit-risk profile in clinical studies of patients with relapsing-remitting multiple sclerosis (RRMS). ESTEEM (NCT02047097) is an ongoing 5-year study characterizing long-term safety and effectiveness of routinely prescribed DMF in MS patients. Patients who discontinued DMF could remain in the study and continue to have data collected per protocol. Post-DMF discontinuation outcomes data can be informative for clinicians and patients who are considering different treatment sequencing strategies.
Objectives: To evaluate safety and efficacy outcomes in patients who discontinued DMF and remained in the ESTEEM study for follow-up.
Methods: Patients for this post-DMF outcomes analysis were those patients who enrolled in ESTEEM and discontinued DMF treatment for any reason but remained in study. Data collected per schedule of assessments include serious adverse events (SAEs), lymphocyte data, and assessment of DMF effectiveness on annualized relapse rate (ARR).
Results: As of April 3, 2019, 5084 patients had ≥1 dose of DMF and qualified for analysis. Of these, 955 (19%) discontinued DMF for any reason but remained in ESTEEM; mean (SD) post-DMF follow-up duration 18.1 (15.8) months, and mean (SD) age was 41.6 (11.3) years. Post-DMF MS treatment choice was available for 96 (10%) patients; mean (SD) washout was 2.7 (3.5) months. Of the patients who discontinued DMF but remained in study, 688 (72%) and 226 (24%) patients had MS relapse and post-DMF lymphocyte data with ≥1 follow-up ALC assessment within 3 months of DMF discontinuation available, respectively. Eleven (2%) patients experienced a total of 16 SAEs; infections (n=4 patients; <1%), and neoplasms (n=3 patients; <1%), were most common. Of the 688 patients with relapse data available, mean post-DMF follow-up was 18.8 (13.6) months; 535 (78%) were relapse-free; 16%, and 6% patients experienced 1 and 2+ relapses, respectively. Estimated post-DMF adjusted annualized relapse rate (ARR) was 0.21, compared to 0.29 on-treatment (1-year prior to DMF discontinuation). In total, 75 (33%) patients had a last recorded absolute lymphocyte count (ALC) <0.91×109/L (lower limit of normal [LLN]) prior to DMF discontinuation; of these, 59 (79%) reached ALC ≥0.8×109/L during the post-DMF follow-up period (mean [SD] duration 14.7 [12.1] months). The median (Q1, Q3) time to ALC recovery ≥0.8×109/L post-DMF treatment was 6.9 (4.4, 17.7) weeks.
Conclusions: Compared to on-treatment relapse rates, patients who discontinued DMF did not experience increase in relapse activity in the post-DMF follow up period. Patients with lymphopenia at discontinuation were able to reach meaningful lymphocyte reconstitution within approximately 2 months. 

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    • Any thoughts on this ?……Yes. We posted on this already
      see Has pharma made a mistake with BTK inhibitors? Are microglia the good guys that shouldn’t be inhibited? Don’t worry. It’s all about Balance.

  • How much of DMF’s treatment effectiveness comes from lymphopenia? Would a reduced dosing regimine that raised 1.0×10^^^^^^^ 9/L still be an effective treatment.

  • Re: “Some people chose dimethyl fumarate and this can cause significant drop in lymphocyte numbers and so this causes a headache for the neuro about switching you to other treatments.”
    Would you consider the duration of DMF-induced lymphopenia to be a factor of importance, or just the ALC as such? E.g. a grade 3-lymphopenia after 1 year, versus a steady grade 2-lymphopenia for 5 years on?

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