Affiliation:
1. Institute of Environmental Medicine Karolinska Institutet Stockholm Sweden
2. Clinical Epidemiology Division, Department of Medicine Solna Karolinska Institutet Stockholm Sweden
3. Med‐X Center for Informatics Sichuan University Chengdu China
4. West China Biomedical Big Data Center West China Hospital, Sichuan University Chengdu China
5. Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden
6. Department of Clinical Neuroscience Karolinska Institutet Stockholm Sweden
7. Department of Neurology Karolinska University Hospital Stockholm Sweden
8. Center for Neurology Academic Specialist Center Stockholm Sweden
Abstract
ObjectiveTo 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).MethodsThis 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.ResultsCompared 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.InterpretationCompared 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