LymphoTEC: a Retrospective Real-World Study on Lymphocyte Reconstitution After Lymphopenia in Patients with Multiple Sclerosis Treated with Dimethyl Fumarate in France

IF 4 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Advances in Therapy Pub Date : 2025-02-19 DOI:10.1007/s12325-024-03092-5

Jérôme de Sèze, Pierre Labauge, Roland Liblau, Mikel Martinez, Thibault Moreau, Laurent Suchet, Patrick Vermersch, Sandra Vukusic, Guillaume Mathey, Laure Michel, Jonathan Ciron, Aurelie Ruet, Elisabeth Maillart, Helene Zephir, Caroline Papeix, Gilles Defer, Mikael Cohen, David Axel Laplaud, Eric Berger, Pierre Clavelou, Eric Thouvenot, Olivier Heinzlef, Jean Pelletier, Claire Giannesini, Olivier Casez, Bertrand Bourre, Abir Wahab, Laurent Magy, Jean-Philippe Camdessanché, Inès Doghri, Céline Labeyrie, Karolina Hankiewicz, Jean-Philippe Neau, Corinne Pottier, Pamela Dobay, Hanyue Li, Seth Levin, Marilyn Gros, Marta Ruiz, Fabien Rollot

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Abstract

Introduction

Dimethyl fumarate (DMF) has demonstrated a favorable benefit–risk profile in patients with relapsing–remitting multiple sclerosis (RRMS). Some patients may develop lymphopenia on DMF; therefore, LymphoTEC evaluated absolute lymphocyte count (ALC) reconstitution after DMF discontinuation.

Methods

LymphoTEC was a retrospective, multicenter study of patients with RRMS in the Observatoire Français de la Sclérose en Plaques registry. Times to ALC reconstitution and lymphopenia were estimated by the Kaplan–Meier method. Univariate and multivariate analyses evaluated factors associated with ALC reconstitution after DMF discontinuation or lymphopenia after DMF initiation. Patients treated with DMF for ≥ 3 months with ≥ 1 ALC in the 6 months before/close to DMF initiation and ≥ 1 ALC during treatment were included.

Results

Overall, 1429 RRMS patients were included; 356 patients developed lymphopenia, of whom 183 discontinued DMF. Overall, ALC decreased by 33% over the first year and plateaued thereafter. The probability of developing lymphopenia was 18.2% after 1 year. In patients with lymphopenia, median times to ALC reconstitution after DMF discontinuation were 3.8 months overall, 4.0 months for Grade 1 lymphopenia, 3.0 months for Grade 2, and 9.7 months for Grade 3. At 12 months, 83.0% had reconstituted ALC. In DMF discontinuers, median time to discontinuation was 1.2 years. There was no increased risk of serious or opportunistic infections in patients with lymphopenia. No cases of progressive multifocal leukoencephalopathy were reported. First ALC reconstitution after DMF discontinuation was associated with diabetes, DMF duration, DMF duration before lymphopenia, and DMF duration after lymphopenia; first lymphopenia after DMF initiation was associated with age and ALC at DMF initiation.

Conclusion

LymphoTEC confirms previous reports on DMF-induced lymphopenia; the benefit–risk profile of DMF remains favorable. Most cases of lymphopenia were not severe and ALC reconstitution typically occurred within 4 months of DMF discontinuation. Patients with shorter and milder lymphopenia had faster ALC reconstitution.

Trial Registration

ClinicalTrials.gov NCT04756687.

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淋巴tec：法国富马酸二甲酯治疗多发性硬化症患者淋巴细胞减少后淋巴细胞重建的回顾性真实世界研究。

富马酸二甲酯（DMF）在复发-缓解型多发性硬化症（RRMS）患者中具有良好的获益-风险特征。部分患者在DMF上可能出现淋巴细胞减少；因此，淋巴tec评估DMF停药后的绝对淋巴细胞计数（ALC）重建。方法：淋巴tec是一项回顾性的、多中心的研究，研究对象是法国结片组织（Observatoire france）登记的RRMS患者。用Kaplan-Meier法估计ALC重建和淋巴细胞减少的时间。单因素和多因素分析评估了DMF停药后ALC重建或DMF启动后淋巴细胞减少的相关因素。纳入DMF治疗≥3个月，DMF开始前/接近6个月ALC≥1，治疗期间ALC≥1的患者。结果：共纳入1429例RRMS患者；356例患者出现淋巴细胞减少，其中183例停用DMF。总体而言，ALC在第一年下降了33%，此后趋于平稳。1年后发生淋巴细胞减少的概率为18.2%。在淋巴细胞减少患者中，DMF停药后ALC重建的中位时间为3.8个月，1级淋巴细胞减少患者为4.0个月，2级淋巴细胞减少患者为3.0个月，3级淋巴细胞减少患者为9.7个月。12个月时，83.0%的患者ALC重建。在停用DMF的患者中，到停用的中位时间为1.2年。淋巴细胞减少患者发生严重感染或机会性感染的风险没有增加。无进展性多灶性脑白质病病例报告。首先，停用DMF后ALC重建与糖尿病、DMF持续时间、淋巴细胞减少前DMF持续时间和淋巴细胞减少后DMF持续时间相关；DMF发生后首次淋巴细胞减少与DMF发生时的年龄和ALC有关。结论：LymphoTEC证实了先前关于dmf诱导淋巴细胞减少的报道；DMF的收益-风险状况仍然有利。大多数病例淋巴细胞减少不严重，ALC重建通常发生在DMF停药后4个月内。时间较短、淋巴细胞减少程度较轻的患者ALC重建较快。试验注册：ClinicalTrials.gov NCT04756687。

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来源期刊

Advances in Therapy 医学-药学

CiteScore

7.20

自引率

2.60%

发文量

353

审稿时长

6-12 weeks

期刊介绍： Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.