ArticleBMC neurology2026
Investigating the role of serum IL-6 in predicting outcomes of b-cell depleting therapy in multiple sclerosis: a retrospective cohort study.
Article in BMC neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundInterleukin-6 (IL-6) plays a pivotal role in autoimmune inflammation through its effects on B-cell differentiation, Th17 expansion, and regulatory T-cell suppression. Given ocrelizumab's (OCR) mechanism of selective CD20
methodsThis exploratory, single-center retrospective cohort study included 73 patients with Relapsing-Remitting MS (RRMS, n = 30) or primary progressive MS (PPMS, n = 43) who initiated OCR at University Hospital Düsseldorf between 2018 and 2025. Baseline serum IL-6 was compared with 86 healthy controls (HC) and correlated with clinical, radiological, and biomarker outcomes over 24 months. Clinical endpoints included confirmed progression independent of relapse activity (PIRA), and relapse-associated worsening (RAW), alongside MRI activity and Serum Neurofilament Light Chain (sNfL) and Serum Glial Fibrillary Acidic Protein (sGFAP) levels. Between-group comparisons used Welch's t-test or Wilcoxon rank-sum test, paired longitudinal comparisons used paired t-tests or Wilcoxon signed-rank tests, and associations between baseline biomarkers and outcomes were evaluated using Cox regression, multivariable linear or logistic regression, and rank-based linear models for IL-6.
resultsBaseline serum IL-6 levels showed no significant differences between the overall MS cohort and HC (p = 0.178), nor between RRMS and PPMS subgroups (p = 0.024; adjusted post-hoc p > 0.05). No baseline biomarker, including IL-6 (HR 1.83; 95% CI 0.73-4.61; p = 0.989), sNfL, and sGFAP predicted disease activity. Longitudinal analysis under OCR revealed largely stable IL-6 concentrations but patients maintaining No Evidence of Disease Activity-3 (NEDA-3) showed 50% reduction in IL-6 at 12 months (mean change - 1.30 pg/mL, p = 0.0318), whereas those with loss of NEDA-3 remained stable (mean change 0.09 pg/mL).
conclusionBaseline serum IL-6 alone is insufficient to predict clinical or radiological outcomes in OCR-treated MS patients. However, the significant longitudinal decline specifically in stable patients suggests that IL-6 dynamics, rather than static baseline measures, may better reflect sustained therapeutic response. These findings underscore the limited utility of serum IL-6 alone as a biomarker and support further exploration of longitudinal, multiparametric approaches.
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