Disease Modifying Therapies – Risk Management Poster Presentation

P0355 - Management of lymphopenia associated with dimethylfumarate and fingolimod (ID 1472)

Speakers
  • B. Bharkhada
Authors
  • B. Bharkhada
  • A. Shields
Presentation Number
P0355
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Dimethylfumarate (DMF) and fingolimod (FTY) are licensed for the treatment of relapsing remitting multiple sclerosis (RRMS). Patients taking these medications may develop severe prolonged lymphopenia. The UK SPC recommends for DMF ‘interruption should be considered in patients with lymphocyte counts <0.5x109/L persisting for more than 6 months’ and for FTY ‘absolute lymphocyte count <0.2x109/l, if confirmed, should lead to treatment interruption until recovery’. There are currently no agreed guidelines for the long term management of patients who develop lymphopenia on DMF and FTY, which can lead to variance in treatment decisions when lymphopenia occurs.

Objectives

To review the number of patients who developed lymphopenia on DMF and FTY and to review the treatment decision for each episode of lymphopenia and determine the outcome, including when switching treatment to another disease modifying treatment (DMT) at The National Hospital for Neurology and Neurosurgery.

Methods

Retrospective audit of patients referred to the pharmacist led off-protocol blood monitoring clinic due to lymphopenia over a one year period (December 2018 to January 2019). Patients were followed up at varied time intervals until a sustained lymphocyte count recovery was achieved. In addition, the outcome of 20 patients on DMF and FTY who were referred to the off-protocol blood monitoring clinic for LC monitoring when switching to another DMT were assessed.

Results

27/478 patients on DMF were referred due to low LC. 12/27 patients experienced grade 3 lymphopenia for more than 6 months. 7/12 patients continued treatment with DMF, of which 3 patients had their dose reduced but still experienced chronic lymphopenia.16/179 patients on FTY were referred due to low LC. 12/16 patients experienced grade 4 lymphopenia for more than 1 month. 4/12 patients stopped FTY and 7/12 patients continued treatment with reduced dose. Mean washout period for 4 patients on DMF referred due to low LC prior to switching DMT was 115 days, however 1 patient had to commence bridging therapy with an injectable as LC remained <1.0 x 109/L for over a year. Mean washout period for 16 patients on FTY referred due to low LC prior to switching DMT was 90.4 days. 4 patients had to commence bridging therapy with an injectable as LC remained <1.0 x 109/L for over 6 months.

Conclusions

Few patients who experience chronic lymphopenia on DMF and FTY stop or switch treatment, and dose reduction of DMTs may not improve LC at the expense of reduced efficacy. The small case series of patients with low lymphocytes switching from DMF or FTY to other DMTs show the washout periods to allow for LC recovery are varied, and there are no clear markers to predict the time it takes for LC to recover. Follow up of this cohort is ongoing to establish if patients who have had treatment with DMF or FTY continue to experience recurrent lymphopenia when switched to another DMT.

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