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Three biomarkers of DMT adverse effects proposed

 

A new review has summarized three potential biomarkers of adverse effects that may occur with disease-modifying therapies used in the treatment of MS (Kreft et al. J Neurol 2022;269:5192-5193). (Free references below.) All results are preliminary and further validation is required.

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CLINICAL CASES IN MS – CASE 6: DIAGNOSTIC DILEMMA

 

Click here to watch Dr. Virender Bhan discuss the case and the responses to the survey.

Joseph is a 28-year-old shipping manager at a local warehouse. He is married and has a three-year-old daughter. He presents in April 2021 following an episode of right sided vision loss, with minimal pain. Exam showed visual acuity 20/400, loss of colour vision and an afferent pupillary defect. The rest of his neuro exam is normal. Brain MRI revealed MS-like white-matter abnormalities with a moderate burden of disease and evidence of right optic neuritis (T2 hyperintensity and contrast enhancement). He was treated with IVMP 1000 mg daily x 3 days, with minimal improvement. There is no history of comorbid conditions and no family history of demyelinating or autoimmune disorders. He has not received a COVID-19 vaccine. Extensive discussion does not change his mind and he says he has no plans to get vaccinated.

The survey is now closed. We received 36 responses. See below for a summary of the answers you provided.

Question 1: What is your provisional diagnosis?
The provisional diagnosis for most respondents was multiple sclerosis (39%) or CIS (28%), although a few considered optic neuritis (19%) or Other (14%).

Question 2: What additional tests would you obtain?
The most common tests obtained were serology (94%), MRI-spinal (86%) and lumbar puncture (86%). A few opted to include OCT (14%), blood/CSF testing to rule out Lyme disease and syphilis (11%), and fluorescein angiography (8%).

Question 3: Would you initiate treatment with a disease-modifying therapy (DMT) at this time?
A majority of respondents said that treatment initiation would be premature since the diagnosis is unclear (52%); another 6% would defer treatment for 6-12 months until a follow-up MRI was obtained. However, many believed that the diagnosis was CIS/MS and would start treatment immediately (31%); another 11% would normally treat immediately but would delay initiation until Joseph was vaccinated.

Question 4: Three months later, Joseph develops interscapular pain followed by numbness and weakness in both legs and he is unable to walk. He has urinary urgency and occasional incontinence. Exam shows moderate paraparesis, sensory level at T6, hyper-reflexia and bilateral Babinski sign. He is hospitalized with a diagnosis of an acute thoracic myelopathy. MRI spine reveals a 2.5-segment enhancing lesion at T4. CSF shows 39 WBCs, mainly lymphocytes. Oligoclonal banding pattern is atypical, 1 band present (not seen in serum). Negative for serum NMO and MOG antibodies. JC virus index is negative. With IVMP 1000 mg x 5 days, he has partial recovery and is now able to walk, but not able to hurry or run. How would you treat this patient?
A majority of respondents would opt for a B cell-depleting therapy, either ocrelizumab or ofatumumab (52%). Many favoured natalizumab (28%), while some preferred cladribine (14%) or an S1PR modulator (6%). None of the respondents selected an injectable DMT or a first-line oral DMT (teriflunomide, DMF).

Question 5: How does Joseph’s COVID-19 vaccination status influence your treatment decision?
The largest proportion of respondents (44%) said they would select the optimal therapy without considering the patient’s COVID vaccination status. However, many (28%) said they would avoid fingolimod, ocrelizumab and rituximab because they may be associated with worse COVID outcomes. Some respondents said they would select an intermittent therapy to minimize the duration of immune suppression (14%). None of the respondents would choose a DMT based on its putative antiviral effects.

View the video commentary by Dr. Virender Bhan.

Additional reading:
Vidal-Jordana et al. Optic Nerve Topography in Multiple Sclerosis Diagnosis: The Utility of Visual Evoked Potentials. Neurology 2021;96:e482-e490.

Is a cell-depleting DMT safe prior to HSCT?

 

Long-acting disease-modifying therapies do not appear to increase the risk of complications following autologous hematopoietic stem cell transplantation (aHSCT), according to a retrospective study from Sweden (Kvistad et al. J Neurol Neurosurg Psychiatry 2022;93:844-848). Read More

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