ImportanceMultiple studies suggest that comorbidity worsens clinically relevant outcomes in multiple sclerosis (MS), including the severity of disability at diagnosis and rate of disability worsening after diagnosis. However, less is known regarding the association of comorbidity with measures of disease activity, such as relapse rate and magnetic resonance imaging lesion accrual, which are relevant to clinicians and clinical trialists.ObjectiveTo evaluate the association of comorbidities with disease activity in clinical trials of disease-modifying therapies (DMTs) in populations with MS.Design, Setting, and ParticipantsA 2-stage meta-analytic approach was used in this cohort study of individual participant data from phase 3 clinical trials of MS DMTs that had 2 years of follow-up and were conducted from November 2001 to March 2018. Data were analyzed from February 2023 to June 2024.ExposureComorbidity burden and individual comorbidities present at trial enrollment, including hypertension; hyperlipidemia; functional cardiovascular disease, ischemic heart, cerebrovascular, and peripheral vascular disease; diabetes; autoimmune thyroid and miscellaneous autoimmune conditions; migraine; lung and skin conditions; depression; anxiety; and other psychiatric disorders.Main Outcomes and MeasuresThe main outcome was evidence of disease activity (EDA) over 2 years of follow-up, defined as confirmed relapse activity, disability worsening, or any new lesions on magnetic resonance imaging.ResultsA total of 16 794 participants with MS were included from 17 clinical trials (67.2% female). Over the 2-year follow-up, 61.0% (95% CI, 56.2%-66.3%; I2 = 97.9%) of the pooled trials had EDA. After adjusting for multiple factors, the presence of 3 or more comorbidities was associated with an increased hazard of EDA (adjusted hazard ratio [AHR], 1.14; 95% CI, 1.02-1.28) compared with no comorbidity. Presence of 2 or more cardiometabolic conditions was also associated with an increased hazard of EDA (AHR, 1.21; 95% CI, 1.08-1.37) compared with no cardiometabolic comorbidity. Presence of 1 psychiatric disorder was associated with an increased hazard of EDA (AHR, 1.07; 95% CI, 1.02-1.14).Conclusions and RelevanceIn this study, a higher burden of comorbidity was associated with worse clinical outcomes in people with MS, although comorbidity could potentially be a partial mediator of other negative prognostic factors. Our findings suggest a substantial adverse association of the comorbidities investigated with MS disease activity and that prevention and management of comorbidities should be a pressing concern in clinical practice.

中文翻译：

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多发性硬化症的合并症和疾病活动度


重要性多项研究表明，合并症会恶化多发性硬化症 （MS） 的临床相关结局，包括诊断时残疾的严重程度和诊断后残疾恶化的比率。然而，关于合并症与疾病活动指标（例如复发率和磁共振成像病灶累积）的相关性，人们对临床医生和临床试验者知之甚少。目的在有 MS.Design、环境和参与者的人群中进行疾病修饰疗法 （DMT） 临床试验中，评估合并症与疾病活动的相关性在这项队列研究中使用了 2 阶段荟萃分析方法，该队列研究对来自 MS DMT 的 3 期临床试验的个体参与者数据进行了 2 年的随访，并于 2001 年 11 月至 2018 年 3 月进行。分析了 2023 年 2 月至 2024 年 6 月的数据。高脂血症;功能性心血管疾病、缺血性心脏、脑血管和外周血管疾病;糖尿病;自身免疫性甲状腺和其他自身免疫性疾病;偏头痛;肺部和皮肤状况;抑郁症;焦虑;和其他精神疾病。主要结局和测量主要结局是 2 年随访期间疾病活动的证据 （EDA），定义为确认复发活动、残疾恶化或磁共振成像上出现任何新病灶。结果共纳入 17 项临床试验的 16 794 例 MS 参与者 （67.2% 为女性）。在 2 年随访中，61.0% （95% CI，56.2%-66.3%;I2 = 97.9%） 的合并试验有 EDA。 在调整多个因素后，与无合并症相比，存在 3 种或更多合并症与 EDA 风险增加相关 （调整后风险比 [AHR]，1.14;95% CI，1.02-1.28）。与无心脏代谢合并症相比，存在 2 种或更多心脏代谢疾病也与 EDA 风险增加相关 （AHR，1.21;95% CI，1.08-1.37）。存在 1 种精神障碍与 EDA 风险增加相关 （AHR，1.07;95% CI，1.02-1.14）。结论和相关性在这项研究中，MS 患者较高的合并症负担与较差的临床结果相关，尽管合并症可能是其他负面预后因素的部分中介。我们的研究结果表明，所调查的合并症与 MS 疾病活动之间存在重大不良关联，预防和管理合并症应该是临床实践中迫切关注的问题。