Yale University, New Haven, CT, USA.
Autoimmunity Center of Excellence, Department of Neurology, University of Michigan Medical School, Ann Arbor, MI, USA.
Mult Scler. 2021 May;27(6):883-894. doi: 10.1177/1352458520937282. Epub 2020 Jul 27.
Delayed-release dimethyl fumarate (DMF) demonstrates sustained efficacy and safety for relapsing forms of MS. Absolute lymphocyte count (ALC) is reduced initially, then stabilizes on treatment.
PROCLAIM, a 96-week, prospective, open-label, phase 3b study, assessed lymphocyte subsets and immunoglobulin (Ig) levels during 48 and 96 weeks (W) of DMF treatment.
Patients received 240 mg DMF BID. Endpoints: lymphocyte subset count changes (primary); Ig isotypes and ALC changes (secondary); adverse events and relationship between ALC changes and ARR/EDSS (exploratory); and neurofilament assessment (ad hoc).
Of 218 patients enrolled, 158 (72%) completed the study. Median ALC decreased 39% from baseline to W96 (BL-W96), stabilizing above the lower limit of normal (baseline: 1.82 × 10/L; W48: 1.06 × 10/L; W96: 1.05 × 10/L). CD4 and CD8 T cells correlated highly with ALC from BL-W96 ( < 0.001). Relative to total T cells, naive CD4 and CD8 T cells increased, whereas CD4 and CD8 central and effector memory T cells decreased. Total IgA, IgG, IgM, and IgG1-4 subclass levels remained stable. Adverse event rates were similar across ALC subgroups. ARR, EDSS, and neurofilament were not correlated with ALCs.
Lymphocyte decreases with DMF were maintained over treatment, yet immunoglobulins remained stable. No increase in infection incidence was observed in patients with or without lymphopenia.
Biogen.
延迟释放富马酸二甲酯（DMF）对复发型多发性硬化症具有持续的疗效和安全性。绝对淋巴细胞计数（ALC）最初降低，然后在治疗过程中稳定。
PROCLAIM 是一项 96 周、前瞻性、开放标签、3b 期研究，评估了 DMF 治疗 48 周和 96 周时淋巴细胞亚群和免疫球蛋白（Ig）水平。
患者接受 240mg DMF BID 治疗。终点：淋巴细胞亚群计数变化（主要终点）；Ig 同种型和 ALC 变化（次要终点）；不良事件以及 ALC 变化与ARR/EDSS 的关系（探索性终点）；和神经丝评估（特别终点）。
在纳入的 218 名患者中，有 158 名（72%）完成了研究。中位数 ALC 从基线到第 96 周（BL-W96）下降了 39%，稳定在正常下限以上（基线：1.82×10/L；W48：1.06×10/L；W96：1.05×10/L）。CD4 和 CD8 T 细胞与 BL-W96 时的 ALC 高度相关（<0.001）。与总 T 细胞相比，幼稚 CD4 和 CD8 T 细胞增加，而 CD4 和 CD8 中央和效应记忆 T 细胞减少。总 IgA、IgG、IgM 和 IgG1-4 亚类水平保持稳定。不良事件发生率在不同 ALC 亚组之间相似。ARR、EDSS 和神经丝与 ALC 无相关性。
DMF 治疗期间维持了淋巴细胞的减少，但免疫球蛋白保持稳定。在有或没有淋巴细胞减少的患者中，未观察到感染发生率增加。
Biogen。
