UCL Institute of Neurology
Department of Neurinflammation

Author Of 2 Presentations

Disease Modifying Therapies – Risk Management Poster Presentation

P0272 - A case series of late onset neutropenia following Ocrelizumab therapy in Multiple Sclerosis (MS) (ID 1918)

Speakers
Presentation Number
P0272
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Ocrelizumab, an anti-CD20 monoclonal antibody similar in action to rituximab, has demonstrated efficacy in relapsing and primary progressive MS. Late onset neutropenia (LON) is a rare, but serious side-effect of rituximab occurring in 1.3% of patients. There only 2 reported cases of LON related to ocrelizumab. A single case of grade 4 LON occurred during the phase three studies.

Objectives

Increase awareness of the features of late onset neutropenia and improve risk management of disease modifying treatments.

Methods

We discuss a case series of 3 treatment naive patients with active RRMS who developed severe LON (grade 4) after ocrelizumab treatment in MS specialist centres in the United Kingdom.

Results

A 31y female presented with neutropenic sepsis (neutrophils 0.0) 115 days after her third ocrelizumab infusion, requiring treatment with intravenous antibiotics and granulocyte colony stimulating factor (G-CSF). Subsequent multiple episodes of recurrent grade 4 neutropenia (neutrophils 0.0-0.2) occurred over the next 6 months, often requiring G-CSF treatment. Bone marrow aspiration demonstrated normocellular granulopoiesis.

A 35y male developed neutropenic sepsis (neutrophils 0.2) 119 days after the first ocrelizumab infusion which recovered rapidly with G-CSF. He received the 2nd and 3rd ocrelizumab doses with no recurrence of neutropenia.

A 22y female developed fever and cough with neutropenia (0.28), 150 days after initial treatment with ocrelizumab. She was treated with IV antibiotics and the neutropenia recovered spontaneously.

Conclusions

The 3 cases demonstrate the spectrum of LON with ocrelizumab. The aetiology of LON is poorly understood, but hypothesised to be mediated by autoimmune destruction, neutrophil apoptosis or failure of release from the bone marrow. The normal bone marrow aspirate suggests peripheral consumption. The cases are important to raise the clinical suspicion of this life threatening complication of disease modifying therapy and the need for serial blood monitoring. Further experience is required to understand risk of recurrence and when it is safe to re-challenge with ocrelizumab.

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Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0739 - Optic chiasm involvement in MS, aquaporin-4 antibody-positive NMOSD, and MOG antibody-associated disease (ID 1441)

Speakers
Presentation Number
P0739
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease

Abstract

Background

Inflammatory demyelination in the anterior optic pathway, including the optic chiasm (OC), occurs frequently in relapsing-remitting multiple sclerosis (RRMS), aquaporin4 (AQP4) antibody (Ab) positive neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein-Ab associated-disease (MOGAD).

Objectives

To evaluate the involvement of the OC in RRMS, AQP4-NMOSD and MOGAD using Magnetization Transfer Ratio (MTR) and explore its relationship with prior optic neuritis (ON).

Methods

We recruited 25 patients with RRMS (16 F, mean age: 44.6 yrs ±11.8, median EDSS: 2.0 [range: 1.0-7.5], mean number of previous episodes of ON: 0.44±0.58, 9 unilateral, 1 bilateral), 13 with AQP4-NMOSD (10 F, mean age: 45.3 yrs ±11.2, median EDSS: 3.0 [1.0-6.5], mean number of ON episodes: 1.54±1.13, 4 unilateral, 6 bilateral), 20 with MOGAD (13 F, mean age: 33.9 yrs ±16.4, median EDSS: 2.0 [0.0-6.5], mean number of ON episodes: 2.85±2.80, 6 unilateral, 11 bilateral) and 29 healthy controls (HC) (23 F, mean age: 35.9 yrs ±12.8). We used T2-weighted, MTon and MToff images to obtain MTR maps of the OC. Age-, sex-, and disease duration-adjusted linear regression models were used to compare the measures between disease and healthy groups (p<0.05).

Results

Chiasmal MTR values in patients with previous ON were lower in AQP4-NMOSD (p=0.040) and MOGAD (p=0.001) than HC but not when compared to patients without previous ON. In patients with RRMS and previous ON, MTR values were lower than patients without prior ON (p=0.003). No differences were found either between patients without ON and HC or between the disease groups.

When considering all patients with demyelinating diseases, patients with previous ON had lower chiasmal MTR values when compared to HC (unilateral: p=0.037; bilateral: p=0.002) and to patients without ON (unilateral: p=0.019; bilateral: p<0.001). This difference persisted when comparing both monophasic and relapsing ON patients to HC (p=0.044; p<0.001) and to patients without ON (p=0.019; p<0.001). No differences were found between patients without history of ON and HC. A correlation was found between MTR values and number of ON episodes (rho=-0.55, p<0.001).

Conclusions

Microstructural damage in the OC correlated with the number of ON episodes across inflammatory demyelinating diseases. A higher number of episodes is associated with lower chiasmal MTR, supporting its role as an accessible target for the assessment of the visual pathway in inflammatory diseases.

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