Disease Modifying Therapies – Risk Management Poster Presentation

P0353 - Lymphopenia in patients treated with dimethyl fumarate. Risk factors and clinical significance. Experience in daily clinical practice (ID 1420)

Speakers
  • G. Valero López
Authors
  • G. Valero López
  • M. Alba Isasi
  • E. Carreón Guarnizo
  • R. Hernandez Clares
  • M. Canovas Iniesta
  • M. Morales De La Prida
  • F. Iniesta Martinez
  • A. Morales Ortiz
  • J. Meca-Lallana
Presentation Number
P0353
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Dimethyl fumarate (DMF) treatment can cause sustained severe lymphopenia, which may be associated with an increased risk of developing infections, leading to discontinuation of treatment.

Objectives

The objective of the study is to identify the frequency and severity of lymphopenia and analyze risk factors for its development in our sample of patients with remitting recurrent multiple sclerosis (RRMS) treated with DMF. Another objective is to analyze whether the appearance of lymphopenia influences the evolution of the disease.

Methods

We carried out a retrospective, descriptive and analytical study of 50 RRMS patients treated with DMF between October 2014 and June 2020, followed for an average of 36.94 months.

Results

A total of 22 patients (44%) developed lymphopenia. Eleven patients developed grade 2 and 7 patients grade 3 lymphopenia. Eighty-two percent of patients developed lymphopenia in the first year. Only in 4 patients did lymphopenia resolve, 3 cases of grade II and 1 case of grade I lymphopenia.

Those patients who developed lymphopenia had a lower absolute lymphocyte count (ALC) before the start of DMF (p 0.013). Although with a trend towards statistical significance (OR 3.88, CI 0.87-17.3. p 0.068) an age at the start of DMF greater than 55 years was not correlated with an increased risk of lymphopenia. Seventy-six percent of the patients had received previous treatments for RRMS, including glatiramer acetate(22.5%), interferon (32.5%), teriflunomide (15.5%) and fingolimod (2.5%), without posing a risk of developing grade II-III lymphopenia.

In our population, the development of lymphopenia was not correlated with a greater probability of reaching NEDA3 at 2 years. Neither was it found to be associated with an increased risk of clinical or radiological activity or discontinuation due to ineffectiveness.

In our sample, lymphopenia was associated with a four times greater risk of developing infections (OR 4.1, CI 1.07-16.1. P 0.033), although all cases were mild. Six patients (12%) discontinued DMF due to sustained grade III lymphopenia. Three of them maintained an ALC of less than 800 at least 6 months after the end of DMF.

Conclusions

In our series, lymphopenia is a frequent adverse effect, it appears especially in the first year and in most cases it remains, even months after stopping DMF. Therefore, surveillance should be increased and control of ALC should be maintained given the increased risk of infection if lymphopenia develops, especially in those patients with lower ACL at baseline.

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