Objective:

We hypothesized that serum biomarker profile is affected by disease modifying therapy (DMT) and certain biomarkers may inform clinicians on best strategy for DMT management. 

Background:

Multiple sclerosis (MS) disease activity is currently monitored in clinical practice through physical exam and interval imaging. Serum biomarkers may provide more a dynamic understanding of current disease activity. The profile of 18 serum biomarkers has been shown to be sensitive in inflammatory disease monitoring (Octave Biosciences MSDA panel). However, no studies have focused on investigating whether DMT may cause alterations in the biomarker profile and whether current DMT should affect how the panel is interpreted in clinical practice. 

Design/Methods:

We collected retrospective data from 377 MSDA tests done on stable patients with MS at UCI. Clinical data, laboratory, imaging, and biomarker data were included in the data set. Data was then analyzed using R. 

Results:

We found that an age-adjusted serum biomarker profile is affected by DMT. B cell activating factor (BAFF) is expected to increase with B cell depleting agents but levels also were found to be altered in following unexpected ways: 1) BAFF levels were significantly higher in ocrelizumab compared to ofatumumab despite similar mechanism of action, 2) BAFF levels correlated with duration of treatment with ocrelizumab but not with ofatumumab, 3) BAFF strongly negatively correlated with IGG levels in ocrelizumab. IGG levels also negatively correlated with length of treatment with ocrelizumab, but not with ofatumumab. Finally, data from longitudinal MSDA testing was used to confirm the correlation between BAFF, IGG and duration of treatment. 

Conclusions:

By examining serum biomarker profile in stable MS patients, we have uncovered a potential predictor of hypogammaglobulinemia in ocrelizumab patients - BAFF. These results may help guide initiation and duration of treatment with ocrelizumab. Further studies are warranted in the mechanistic role of BAFF in pathogenesis of iatrogenic hypogammaglobulinemia.