University of Massachusetts Medical School
Neurology

Author Of 2 Presentations

Biomarkers and Bioinformatics Poster Presentation

P0110 - Modulation of cerebrospinal fluid immunoglobulins by ocrelizumab treatment (ID 1597)

Abstract

Background

Intrathecal production of immunoglobulin (Ig) and the presence of cerebrospinal fluid (CSF)–specific oligoclonal bands (OCBs) are hallmarks of multiple sclerosis (MS) that persist throughout the disease course and treatment.

Objectives

To describe baseline (BL) correlations of CSF IgM and IgG production with CSF biomarkers and to assess the pharmacodynamic effects of ocrelizumab (OCR) treatment on these parameters in patients with relapsing MS (RMS) from the Ocrelizumab Biomarker Outcome Evaluation (OBOE) study (NCT02688985).

Methods

Seventy-nine of 100 total patients with RMS had available BL CSF samples for assessment of IgG OCBs, IgG and IgM (measured at University Medical Center Göttingen), with demographic, MRI and clinical parameters representative of the total RMS population. CSF samples at either 12 (n=22), 24 (n=24) or 52 (n=17) weeks postdose and from a 12-week reference arm (no OCR; n=16) were assessed for longitudinal changes.

Results

Median (interquartile range [IQR]) CSF levels at BL were as follows: IgG index, 0.79 (0.63–1.28); IgM index, 0.19 (0.11–0.33); CD3+ T cell number, 2.52 (0.80–5.61) cells/µL; CXCL13, 9.89 (3.91–31.50) pg/mL; CCL19, 47.95 (31.09–70.86) pg/mL; neurofilament light chain (NfL) 1280.0 (828.1–2968.9) pg/mL. At BL, IgG index and IgM index correlated moderately with levels of B cells (r=0.65, r=0.4 respectively), T cells (r=0.54, r=0.3 respectively) and CXCL13 (r=0.58, r=0.43 respectively), but not CCL19 or NfL. IgG index tended to decrease with OCR treatment and was significantly reduced by 52 weeks (n=17/79; median [IQR] change from BL −9.5% [−20.4% to −0.1%]; p<0.02) compared with stable levels in the reference arm. While IgG OCBs were detected at BL in all patients, IgG OCBs tended to decrease with OCR treatment, with three of 17 patients having no detectable IgG OCBs at 52 weeks. Reductions in IgM index were not observed with OCR treatment.

Conclusions

Baseline CSF levels of B cells, T cells and CXCL13 correlated with IgG index and to a lesser degree IgM index in patients with RMS from the OBOE study. Significant reductions were observed in IgG index with OCR treatment, along with a trend toward reduced OCBs, with three patients showing no detectable OCBs. These data suggest that OCR impacts CSF Ig production, a hallmark of MS not previously thought to be affected by B-cell depletion therapy. These 1-year observations need to be confirmed with longer-term data and correlated with clinical response.

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Comorbidities Poster Presentation

P0446 - Comorbid Anxiety, Depression, and Fatigue Symptoms by Disease Modifying Therapy: A National Multiple Sclerosis Cohort (ID 396)

Presentation Number
P0446
Presentation Topic
Comorbidities

Abstract

Background

Psychiatric comorbidities are common in multiple sclerosis (MS) and are associated with diminished quality of life and non-adherence to disease-modifying therapy (DMT). Depression is linked to immune activation in inflammatory disorders. We hypothesized that persons with self-reported MS not receiving DMT and those on lower efficacy DMT (low [LED] and moderate [MED]) had more symptoms of anxiety, depression, and fatigue, as compared to those on DMT and on high efficacy DMT (HED).

Objectives

Our team sought to determine if symptoms of depression, anxiety, and fatigue in MS correlate with the use and efficacy of DMT.

Methods

We developed a web-based survey including the Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder 7-item (GAD-7) scale, and the Modified Fatigue Impact Scale 5-item version (MFIS-5). Invitations to complete the survey were distributed electronically by MS organizations. DMTs were classified in LED (interferon beta-1a, interferon beta-1b, peginterferon beta-1a, glatiramer acetate), MED (teriflunomide, fingolimod, siponimod, dimethyl fumarate), and HED (alemtuzumab, ocrelizumab, rituximab, natalizumab, cladribine). Analyses were conducted using linear models adjusted for age, sex, ethnicity, disease duration, employment status, and whether the individual has an MS provider.

Results

2121 persons completed the survey (age 51.1±12.4 years, 18% male, and 52% have had MS for >10 years). 1650 were on DMT (465 LED, 546 MED, 624 HED, 15 other). MFIS-5 and GAD-7 scores were lower for those on DMT as compared to those not on DMT (for MFIS-5: 0.79 points lower, 95% CI -1.37, -0.21; p=0.007; for GAD-7: 0.68 points lower; 95% CI -1.29, -0.07, p=0.03). Those on LED had -1.18 (95% CI -1.97, -0.38; p=0.004) lower PHQ-9 scores compared to those on no DMT. Among individuals on a DMT, those on HED had higher MFIS-5 and PHQ-9 scores relative to those on LED (for MFIS-5: 1.78 points higher, 95% CI 1.13, 2.24, p<0.001; for PHQ-9: 1.00 points higher; 95% CI 0.25, 1.74, p=0.009).

Conclusions

In this cross-sectional study, untreated patients had more fatigue and anxiety than those on DMT and greater depression than those on LED. LED-treated patients had lower fatigue and depression scores compared to those on HED. Indication biases may have influenced our results; longitudinal studies taking into account prior DMT history and indicators for specific DMTs should evaluate whether certain DMT classes affect future depression, anxiety, or fatigue levels.

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