Predictors of lymphocyte count recovery after dimethyl fumarate-induced lymphopenia in people with multiple sclerosis

Matteo Lucchini,Claudio Gasperini,Viviana Nociti,Elisabetta Ferraro,Antonio Cortese,Antonella Conte,Carla Tortorella,Marco Salvetti,Antonio Ianniello,Giorgia Elia,Roberta Fantozzi,Maria Chiara Buscarinu,Carlo Pozzilli,Girolama Alessandra Marfia,Doriana Landi,Massimiliano Mirabella,Luca Prosperini,Diego Centonze

doi:10.1007/s00415-021-10412-0

Abstract

BackgroundDimethyl fumarate (DMF) is an oral drug approved for Relapsing Multiple Sclerosis (RMS) patients. Grade III lymphopenia is reported in 5–10% DMF-treated patients. Data on lymphocyte count (ALC) recovery after DMF withdrawal following prolonged lymphopenia are still scarce.ObjectivesTo characterize ALC recovery and to identify predictors of slower recovery after DMF interruption.MethodsMulticenter data from RMS patients who started DMF and developed lymphopenia during treatment were collected. In patients with grade II–III lymphopenia, ALCs were evaluated from DMF withdrawal until reaching lymphocyte counts > 800/mm3.ResultsAmong 1034 patients who started DMF, we found 198 (19.1%) patients with lymphopenia and 65 patients (6.3%) who discontinued DMF due to persistent grade II–III lymphopenia. Complete data were available for 51 patients. All patients recovered to ALC > 800 cells/mm3 with a median time of 3.4 months. Lower ALCs at DMF suspension (HR 0.98; p = 0.005), longer disease duration (HR 1.29; p = 0.014) and prior exposure to MS treatments (HR 0.03; p = 0.025) were found predictive of delayed ALC recovery.ConclusionALC recovery after DMF withdrawal is usually rapid, nevertheless it may require longer time in patients with lower ALC count at DMF interruption, longer disease duration and previous exposure to MS treatments, potentially leading to delayed initiation of a new therapy.

Highlights

Several injectable, oral, and infusible Disease-Modifying Drugs (DMDs) approved for the treatment of Relapsing Multiple Sclerosis (RMS) can result in a decrease of absolute lymphocyte count (ALC) with different mechanism of action [1]
Older age (HR 1.03; 95% CIs 1.02–1.05; p < 0.001) and female sex (HR 1.55; 95% CIs 1.10–2.18; p = 0.012) were significant independent baseline predictors of lymphopenia development during Dimethyl fumarate (DMF) treatment (Table 2) through Cox regression analysis
Through a binary logistic regression analysis, we found that lower ALC at DMF suspension (HR 0.99; 95% CIs 0.98–0.99; p = 0.008), longer disease duration (HR 1.13; 95% CIs 1.01–1.27; p = 0.031) and prior exposure to MS treatments (HR 0.08; 95% CIs 0.01–0.54; p = 0.01) were significant predictors of slower ALC recovery (Table 4)

Summary

Introduction

Oral, and infusible Disease-Modifying Drugs (DMDs) approved for the treatment of Relapsing Multiple Sclerosis (RMS) can result in a decrease of absolute lymphocyte count (ALC) with different mechanism of action [1]. Dimethyl fumarate (DMF) is an oral drug approved for Relapsing Multiple Sclerosis (RMS) patients. Data on lymphocyte count (ALC) recovery after DMF withdrawal following prolonged lymphopenia are still scarce. In patients with grade II–III lymphopenia, ALCs were evaluated from DMF withdrawal until reaching lymphocyte counts > 800/mm. Conclusion ALC recovery after DMF withdrawal is usually rapid, it may require longer time in patients with lower ALC count at DMF interruption, longer disease duration and previous exposure to MS treatments, potentially leading to delayed initiation of a new therapy

Methods

Results

Discussion

Conclusion