To investigate whether κ-free light chain (FLC) index determined at disease onset predicts multiple sclerosis (MS) disease activity over a period of 10 years. 

κ-FLC index predicts short-term disease activity in early MS. The prognostic value of this biomarker over the long-term is largely unknown. 

Patients with a first demyelinating event of the central nervous system who had cerebrospinal fluid (CSF) and serum sampling at disease onset were followed for 10 (±5) years. At baseline age, sex, disease duration as well as number of T2 hyperintense lesions (T2L) and contrast-enhancing lesions (CEL) on MRI were determined. During follow-up, the occurrence of relapse, Expanded Disability Status Scale (EDSS) scores and the initiation of disease-modifying treatment (DMT) were registered. κ-FLC were measured by nephelometry and κ-FLC index was calculated as (CSF κ-FLC/serum κ-FLC)/albumin quotient. 

A total of 64 patients with a median age of 32 years (25^th-75^th percentile: 27-39) and a female predominance of 75% were followed over median of 113 (90-129) months. Forty-six (72%) patients experienced relapse and 30 (47%) showed disability worsening during follow-up. Multivariable Cox regression analysis adjusted for age, sex, disease duration, number of T2L, CEL, and the administration of DMT, revealed that κ-FLC index predicts time to relapse (Hazard ratio (HR): 1.45, lower limit (LL) of 95%-confidence interval (CI): 1.002, per increase of 100, p=0.049) and disability worsening (HR: 1.86, LL-CI: 1.22, p=0.008). At year 10, the estimated chance to remain free of relapse was decreased by 40% in patients with high κ-FLC index (>100) compared to patients with low κ-FLC index (≤100), the probability to remain without disability worsening was 27% lower. 

κ-FLC index predicts long-term MS disease activity and disability worsening independent of other risk factors.