Inselspital Bern, University Hospital and University of Bern

Author Of 3 Presentations

Biomarkers and Bioinformatics Poster Presentation

P0154 - Serum Neurofilament light chain captures and predicts disability progression independent of relapses (PIRA) in multiple sclerosis (ID 809)

Abstract

Background

In relapsing MS, blood NfL has emerged as a promising biomarker of disease activity and worsening. The ability of serum NfL (sNfL) to detect relapse-independent disability progression is less well established.

Objectives

We investigated whether patients followed in the Swiss Multiple Sclerosis Cohort (SMSC) without any relapses during follow-up, had higher sNfL levels when experiencing confirmed disability progression independent of relapses (PIRA) as compared to stable patients. Secondly, we explored whether baseline (BL) sNfL could predict PIRA.

Methods

BL and 6- or 12-monthly follow-up sNfL were measured by Simoa NF-light® assay in 4608 samples from 806 relapse-free MS patients and 8865 serum samples from 4133 healthy controls (median age 45 yrs). Age-dependent sNfL z-scores (sNfLz) were modeled in healthy controls using a generalised additive model for location scale and shape to reflect the deviation of a patient sNfL value from the mean value of same age healthy controls. PIRA was defined as an EDSS increase of ≥1.5 steps if baseline EDSS 0, ≥1.0 if 1.0-5.5, or ≥0.5 if >5.5, confirmed after ≥6 months. We used mixed effects models to investigate the association between PIRA, clinical parameters, disease modifying treatment, and log(sNfL) as dependent variable at each sampling. The predictive value of BL sNfLz was investigated by uni- and multivariable Cox proportional hazards models.

Results

806 (4608 samples) of 1399 patients in the SMSC did not experience relapses during a median follow-up of 4.7 years (57.6%; BL: 715 RRMS, 43 SPMS, 48 PPMS; median age 42 yrs; samples/patient: 5; EDSS 2.0). PIRA occurred in 153/806 (19.0%). In a multivariable model, sNfL was positively associated with age (1.7%/year [95%CI 1.5;2.0], p<0.001) and EDSS at BL (7.6%/step, [5.8;9.6], p<0.001), whereas it was decreased when sampled during monoclonal antibody therapy (-10.8%, [-14.7;-6.6], p<0.001) or oral MS treatments (-10.4%, [-14.1;-6.5%], p<0.001) as compared to untreated timepoints. Importantly, patients experiencing PIRA had 11.6% higher sNfL levels, compared with stable patients (4.5;19.2, p=0.001). The hazard of future PIRA increased by 23.5% (8.3;40.8, p=0.002) per 1 standard deviation higher BL sNfLz. This finding was confirmed after adjusting for age, EDSS score and treatment at BL (27.8%, [11.5;46.5], p<0.001; sNfLz > 2: 2.5-fold risk [95%CI 1.7-3.9], p<0.001 for PIRA event vs. sNfLz < 2).

Conclusions

Our data support the value of sNfL to capture and predict neuro-axonal injury leading to disability progression independent from relapses.

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Disease Modifying Therapies – Risk Management Poster Presentation

P0359 - Natalizumab and eosinophilia: epidemiological characteristics and clinical associations (ID 1442)

Speakers
Presentation Number
P0359
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Natalizumab is used as an immunomodulatory treatment in relapsing-remitting multiple sclerosis (RRMS). Blood eosinophilia as an adverse effect has been described.

Objectives

We aim to describe the frequency of blood eosinophilia and associated clinical symptoms in our monocentric cohort of natalizumab treated patients with relapsing remitting Multiple Sclerosis.

Methods

In our tertiary neurological care centre in Switzerland, we retrospectively longitudinally identified 115 natalizumab-treated and 116 untreated RRMS patients with eosinophil counts since July 2016 with our pharmacovigilance system and compared eosinophil counts, clinical symptoms and patient demographics.

Results

In total, 44/115 natalizumab-treated patients (38%) developed eosinophilia (>0.4 G/l), which occurred significantly more frequently compared to 116 untreated MS patients (n=3; 3%). Of 44 natalizumab-treated patients with eosinophilia, 43 remained asymptomatic; one patient one patient developed an eosinophilic pneumonia after 2 infusions of natalizumab, which resolved without sequelae after cessation. All untreated MS patients with eosinophilia remained asymptomatic.

Conclusions

Our cohort confirmed that eosinophilia is a potential side effect of natalizumab in RRMS patients and most commonly remains asymptomatic. However, in one of our natalizumab-treated patients (0.9% of all patients), an eosinophilic pneumonia occurred as a rare but severe side effect. Physicians should be vigilant for symptoms of an eosinophilic disease in natalizumab-treated patients. Further studies on drug safety in real-life settings using automated big data approaches are warranted to better describe drug-associated adverse effects.

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Observational Studies Poster Presentation

P0890 - Neurologic manifestations of IgG4-related disease: A single-center case series (ID 1379)

Speakers
Presentation Number
P0890
Presentation Topic
Observational Studies

Abstract

Background

IgG4-related disease (IgG4-RD) is a multisystem disorder, which can affect nearly every organ system. Although involvement of the nervous system is commonly described, systematic descriptions of neurological involvement are rare.

Objectives

Our objective was to describe the characteristics of patients diagnosed with IgG4-RD presenting with neurologic involvement.

Methods

Patients with IgG4-RD were retrospectively identified by screening medical records of all patients, who had signed general consent, treated at the outpatient neurology clinic of our university hospital.

Results

Since 2012, we found 12 cases of IgG4-RD of whom eight cases presented with neurologic manifestations. Of those 6/8 (75%) patients were male. Mean age at symptom onset was 62 years (range: 35 - 81 years). In 2/8 (25%) of patients, neurologic presentation was the only disease manifestation and consisted of pachymeningitis, cranial neuropathy affecting cranial nerves II, V and VII, peripheral neuropathy, myalgia, carotid stenosis and cerebral ischemia. Lumbar puncture was performed in 5/8 (62%) patients and showed elevated cell count in 1 patient (range: 2- 9 M/l). Mean serum IgG4 concentration was 4.58 g/l (range 1.35 - 12.3 g/l) and was elevated in 7/8 patients. In the patient with normal IgG4 values biopsy was compatible with IgG4-RD. Total serum IgG was elevated in 4/8 (50%) patients with a mean of 14.9 g/l (range 8.92 – 21.6 g/l). Immunotherapy was started in 7/8 (87%) patients. Three patients received a high dose steroid monotherapy; other treatments were rituximab, methotrexate and leflunomide. Under these therapies, the outcome was favorable in 4/8 (50%) of patients, 3/8 (38%) remained unchanged and one patient succumbed to an unrelated pathology (colorectal cancer).

Conclusions

IgG4-related neurologic disease can manifest with multisystem involvement, but isolated neurologic manifestation is possible. If diagnosis is considered in patients with normal IgG4 levels biopsy should be obtained.

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