Yihan Hu MSc, Thomas Frisell PhD, Peter Alping MD, PhD, Huan Song MD, PhD, Yudi Pawitan PhD, Fang Fang MD, PhD, Fredrik Piehl MD, PhD
{"title":"医院治疗感染与多发性硬化症患者残疾恶化的风险。","authors":"Yihan Hu MSc, Thomas Frisell PhD, Peter Alping MD, PhD, Huan Song MD, PhD, Yudi Pawitan PhD, Fang Fang MD, PhD, Fredrik Piehl MD, PhD","doi":"10.1002/ana.27026","DOIUrl":null,"url":null,"abstract":"<div>\n \n <section>\n \n <h3> Objective</h3>\n \n <p>To investigate the association between infections and disability worsening in people with multiple sclerosis (MS) treated with either B-cell depleting therapy (rituximab) or interferon-beta/glatiramer acetate (IFN/GA).</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>This cohort study spanned from 2000 to 2021, using data from the Swedish MS Registry linked to national health care registries, comprising 8,759 rituximab and 7,561 IFN/GA treatment episodes. The risk of hospital-treated infection was estimated using multivariable Cox models. The association between infections and increase in Expanded Disability Status Scale (EDSS) scores was assessed using a doubly robust generalized estimating equations model. Additionally, a piece-wise exponential model analyzed events of increased disability beyond defined cut-off values, controlling for relapses, and MRI activity.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Compared with IFN/GA, rituximab displayed increased risk of both inpatient- and outpatient-treated infections (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.50–2.90 and HR, 1.37; 95% CI, 1.13–1.67, respectively). An inpatient-treated infection was associated with a 0.19-unit increase in EDSS (95% CI, 0.12–0.26). Degree of worsening was greatest for progressive MS, and under IFN/GA treatment, which unlike rituximab, was more commonly associated with MRI activity. After controlling for relapses and MRI activity, inpatient-treated infections were associated with disability worsening in people with relapsing–remitting MS treated with IFN/GA (HR, 2.01; 95% CI, 1.59–2.53), but not in those treated with rituximab.</p>\n </section>\n \n <section>\n \n <h3> Interpretation</h3>\n \n <p>Compared to IFN/GA, rituximab doubled the infection risk, but reduced the risk of subsequent disability worsening. Further, the risk of worsening after hospital-treated infection was greater with progressive MS than with relapsing–remitting MS. Infection risk should be considered to improve long term outcomes. ANN NEUROL 2024;96:694–703</p>\n </section>\n </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":null,"pages":null},"PeriodicalIF":8.1000,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27026","citationCount":"0","resultStr":"{\"title\":\"Hospital-Treated Infections and Risk of Disability Worsening in Multiple Sclerosis\",\"authors\":\"Yihan Hu MSc, Thomas Frisell PhD, Peter Alping MD, PhD, Huan Song MD, PhD, Yudi Pawitan PhD, Fang Fang MD, PhD, Fredrik Piehl MD, PhD\",\"doi\":\"10.1002/ana.27026\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <section>\\n \\n <h3> Objective</h3>\\n \\n <p>To investigate the association between infections and disability worsening in people with multiple sclerosis (MS) treated with either B-cell depleting therapy (rituximab) or interferon-beta/glatiramer acetate (IFN/GA).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>This cohort study spanned from 2000 to 2021, using data from the Swedish MS Registry linked to national health care registries, comprising 8,759 rituximab and 7,561 IFN/GA treatment episodes. The risk of hospital-treated infection was estimated using multivariable Cox models. The association between infections and increase in Expanded Disability Status Scale (EDSS) scores was assessed using a doubly robust generalized estimating equations model. Additionally, a piece-wise exponential model analyzed events of increased disability beyond defined cut-off values, controlling for relapses, and MRI activity.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Compared with IFN/GA, rituximab displayed increased risk of both inpatient- and outpatient-treated infections (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.50–2.90 and HR, 1.37; 95% CI, 1.13–1.67, respectively). An inpatient-treated infection was associated with a 0.19-unit increase in EDSS (95% CI, 0.12–0.26). Degree of worsening was greatest for progressive MS, and under IFN/GA treatment, which unlike rituximab, was more commonly associated with MRI activity. After controlling for relapses and MRI activity, inpatient-treated infections were associated with disability worsening in people with relapsing–remitting MS treated with IFN/GA (HR, 2.01; 95% CI, 1.59–2.53), but not in those treated with rituximab.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Interpretation</h3>\\n \\n <p>Compared to IFN/GA, rituximab doubled the infection risk, but reduced the risk of subsequent disability worsening. Further, the risk of worsening after hospital-treated infection was greater with progressive MS than with relapsing–remitting MS. Infection risk should be considered to improve long term outcomes. 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Hospital-Treated Infections and Risk of Disability Worsening in Multiple Sclerosis
Objective
To investigate the association between infections and disability worsening in people with multiple sclerosis (MS) treated with either B-cell depleting therapy (rituximab) or interferon-beta/glatiramer acetate (IFN/GA).
Methods
This cohort study spanned from 2000 to 2021, using data from the Swedish MS Registry linked to national health care registries, comprising 8,759 rituximab and 7,561 IFN/GA treatment episodes. The risk of hospital-treated infection was estimated using multivariable Cox models. The association between infections and increase in Expanded Disability Status Scale (EDSS) scores was assessed using a doubly robust generalized estimating equations model. Additionally, a piece-wise exponential model analyzed events of increased disability beyond defined cut-off values, controlling for relapses, and MRI activity.
Results
Compared with IFN/GA, rituximab displayed increased risk of both inpatient- and outpatient-treated infections (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.50–2.90 and HR, 1.37; 95% CI, 1.13–1.67, respectively). An inpatient-treated infection was associated with a 0.19-unit increase in EDSS (95% CI, 0.12–0.26). Degree of worsening was greatest for progressive MS, and under IFN/GA treatment, which unlike rituximab, was more commonly associated with MRI activity. After controlling for relapses and MRI activity, inpatient-treated infections were associated with disability worsening in people with relapsing–remitting MS treated with IFN/GA (HR, 2.01; 95% CI, 1.59–2.53), but not in those treated with rituximab.
Interpretation
Compared to IFN/GA, rituximab doubled the infection risk, but reduced the risk of subsequent disability worsening. Further, the risk of worsening after hospital-treated infection was greater with progressive MS than with relapsing–remitting MS. Infection risk should be considered to improve long term outcomes. ANN NEUROL 2024;96:694–703
期刊介绍:
Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.