Frahm Niklas, Ellenberger David, Stahmann Alexander, Fneish Firas, Lüftenegger Daniel, Salmen Hans C, Schirduan Ksenija, Schaak Tom P A, Flachenecker Peter, Kleinschnitz Christoph, Paul Friedemann, Krefting Dagmar, Zettl Uwe K, Peters Melanie, Warnke Clemens
German MS Registry, MS Forschungs- und Projektentwicklungs-gGmbH (MS Research and Project Development gGmbH [MSFP]), Krausenstr. 50, Hannover, Niedersachsen 30171, Germany.
German MS Registry, MS Forschungs- und Projektentwicklungs-gGmbH (MS Research and Project Development gGmbH [MSFP]), Hannover, Germany.
Ther Adv Neurol Disord. 2024 Mar 29;17:17562864241239740. doi: 10.1177/17562864241239740. eCollection 2024.
The spectrum of disease-modifying therapies (DMTs) for people with multiple sclerosis (PwMS) has expanded over years, but data on treatment strategies is largely lacking. DMT switches are common clinical practice.
To compare switchers and non-switchers, characterize the first DMT switch and identify reasons and predictors for switching the first DMT.
Data on 2722 PwMS from the German MS Registry were retrospectively analyzed regarding sociodemographic/clinical differences between 1361 switchers (PwMS discontinuing the first DMT) and non-switchers matched according to age, sex, and observation period. Frequencies of first and second DMTs were calculated and switch reasons identified. Predictors for DMT switches were revealed using univariable and multivariable regression models.
Switchers and non-switchers differed significantly regarding time to first DMT, education, calendar period of the first DMT start (2014-2017 2018-2021), first DMT class used [mild-to-moderate efficacy (MME) high-efficacy (HE) DMT], time on first DMT, and disease activity at first DMT start or cessation/last follow-up. The majority of PwMS started with MME DMTs (77.1%), with the most common being glatiramer acetate, dimethyl/diroximel fumarate, and beta-interferon variants. Switchers changed treatment more often to HE DMTs (39.6%), most commonly sphingosine-1-phosphate receptor modulators, anti-CD20 monoclonal antibodies, and natalizumab. Fewer PwMS switched to MME DMTs (35.9%), with the most common being dimethyl/diroximel fumarate, teriflunomide, or beta-interferon. Among 1045 PwMS with sufficient data (76.8% of 1361 switchers), the most frequent reasons for discontinuing the first DMT were disease activity despite DMT (63.1%), adverse events (17.1%), and patient request (8.3%). Predictors for the first DMT switch were MME DMT as initial treatment [odds ratio (OR) = 2.83 (1.76-4.61), < 0.001; reference: HE DMT], first DMT initiation between 2014 and 2017 [OR = 11.55 (6.93-19.94), < 0.001; reference: 2018-2021], and shorter time on first DMT [OR = 0.22 (0.18-0.27), < 0.001].
The initial use of MME DMTs was among the strongest predictors of DMT discontinuation in a large German retrospective MS cohort, arguing for the need for prospective treatment strategy trials, not only but also on the initial broad use of HE DMTs in PwMS.
多年来，用于多发性硬化症患者（PwMS）的疾病修正疗法（DMTs）种类有所增加，但关于治疗策略的数据大多缺乏。DMT转换是常见的临床操作。
比较转换者和未转换者，描述首次DMT转换的特征，并确定首次DMT转换的原因和预测因素。
回顾性分析德国多发性硬化症登记处2722例PwMS的数据，分析1361例转换者（停用首次DMT的PwMS）与根据年龄、性别和观察期匹配的未转换者之间的社会人口统计学/临床差异。计算首次和第二次DMT的使用频率，并确定转换原因。使用单变量和多变量回归模型揭示DMT转换的预测因素。
转换者和未转换者在首次使用DMT的时间、教育程度、首次开始使用DMT的日历期（2014 - 2017年与2018 - 2021年）、首次使用的DMT类别[轻度至中度疗效（MME）与高效（HE）DMT]、首次使用DMT的时间以及首次开始使用DMT或停止使用/最后一次随访时的疾病活动度方面存在显著差异。大多数PwMS最初使用MME DMT（77.1%），最常见的是醋酸格拉替雷、富马酸二甲酯/二羟丙茶碱和β-干扰素变体。转换者更常将治疗转换为HE DMT（39.6%），最常见的是鞘氨醇-1-磷酸受体调节剂、抗CD20单克隆抗体和那他珠单抗。较少的PwMS转换为MME DMT（35.9%），最常见的是富马酸二甲酯/二羟丙茶碱、特立氟胺或β-干扰素。在1045例有足够数据的PwMS中（1361例转换者中的76.8%），停用首次DMT的最常见原因是尽管使用了DMT仍有疾病活动（63.1%）、不良事件（17.1%）和患者要求（8.3%）。首次DMT转换的预测因素是初始治疗使用MME DMT[比值比（OR）=2.83（1.76 - 4.61），P<0.001；参考：HE DMT]、2014年至2017年开始首次DMT[OR = 11.55（6.93 - 19.94），P<0.001；参考：2018 - 2021年]以及首次DMT使用时间较短[OR = 0.22（0.18 - 0.27），P<0.001]。
在一个大型德国回顾性多发性硬化症队列中，初始使用MME DMT是DMT停用的最强预测因素之一，这表明不仅需要进行前瞻性治疗策略试验，还需要对PwMS广泛初始使用HE DMT进行研究。
