vascular surgery common practice headline...headline swedish neuroscience institute program title...

HeadlineSwedish Neuroscience Institute

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Vascular SurgerySwedish Heart & Vascular Institute

Retreat

Rocco G. Ciocca, M.D. FACSChief of Vascular Surgery

Common practiceApproach to MS therapies and their risks

among specialists in Pacific NW

2019 MS Regional SummitPavle Repovic, MD, PhDNeurologist, Swedish MS Center


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Presentation outline

https://bit.ly/2CLN23b

1. MS relapse management

2. Risk assessment prior to treatment

3. On-treatment risk reduction

4. Treatment discontinuation/switching

5. Cases and synthesis


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Disclosure

• Most of the practices discussed in this presentation are not specifically recommended by the FDA. Instead, they represent individual practitioners’ approaches.



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Introduction/Methods

• Questionnaire

– Open-ended

– Anonymous



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MS Relapse management

A. First line therapy 1 2 3 4 5

1) Route

▪ IV >, = or < PO route IV IV PO = IV

▪ PO formulation prednisone 1250 mg ✓ ✓ ✓ ✓ ✓

2) Location: Infusion facility > or < home I = I H I

3) Taper

A. Second line therapy

4) ACTH gel

5) 2nd course of steroid ✓ ✓

5) Plasma exchange ✓ ✓ ✓ ✓ ✓

▪ Number of exchange sessions, qod 5 5 5 5 5



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Dimethyl fumarate (Tecfidera)

A. Prior to treatment 1 2 3 4 5

▪ CBC with differential and LFT/CMP ✓ ✓ ✓ ✓ ✓

▪ Alternative titration

▪ 120 mg daily x 2 wks, 240 mg daily x 2 wks, full dose ✓ ✓ ✓

▪ 120 mg daily x 1 wk, 240 mg daily x 1 wk, 120 mg/240 mg x 1 wk, full dose ✓ ✓

▪ JCV antibody

B. On-treatment 1 2 3 4 5

▪ CBC with differential and LFT ✓ ✓ ✓ ✓ ✓

▪ JCV antibody if lymphopenic ✓ ✓ ✓ ✓ ✓



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Fingolimod (Gilenya)


1) LABS

▪ CBC w diff, CMP, VZV IgG (prescribing information) ✓ ✓ ✓ ✓ ✓

▪ JCV antibody ✓ ✓ ✓ ✓ ✓

▪ Quantiferon TB, HIV, Hep B/C ✓ ✓

2) OTHER

▪ Ophthalmology evaluation prior to FDO ✓ ✓ ✓ ✓ ✓

▪ Cardiologist-interpreted EKG (in addition to day of FDO) ✓ ✓ ✓ ✓ ✓

▪ VZV vaccination if no evidence of immunity ✓ ✓ ✓ ✓ ✓


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Fingolimod (Gilenya)

B. On treatment 1 2 3 4 5

1) LABS

▪ CBC w diff, CMP q3-6 months ✓ ✓ ✓ ✓ ✓

▪ JCV antibody ✓

2) OTHER

▪ Ophthalmology evaluation @ 3-4 months ✓ ✓ ✓ ✓ ✓

▪ Dermatology exam annually ✓ ✓ ✓

▪ Alternate dosing if low ALC (omit weekend or qod) ✓ ✓ ✓


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Natalizumab (Tysabri)


1) LABS

▪ CBC w diff, CMP ✓ ✓ ✓ ✓ ✓

▪ JCV antibody ✓ ✓ ✓ ✓ ✓

▪ HIV ✓

2) OTHER

▪ Baseline MRI ✓ ✓ ✓ ✓ ✓


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Natalizumab (Tysabri)


1) LABS


▪ JCV antibody q6 months ✓

▪ JCV antibody q3 months ✓ ✓ ✓ ✓

▪ JCV antibody q2 months ✓

▪ JCV antibody q1 month if JCV- and prior IS+ ✓

2) OTHER

▪ Brain MRI – annual ✓ ✓ ✓ ✓ ✓

▪ Brain MRI – q 6 months for JCV+ ✓ ✓

▪ Extended interval dosing (q6-8wks) for JCV+ ✓ ✓ ✓ ✓


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Ocrelizumab (Ocrevus)A. Prior to treatment 1 2 3 4 5

1) LABS

▪ CBC w diff, CMP ✓ ✓ ✓ ✓ ✓

▪ Hepatitis B and C serology ✓ ✓ ✓ ✓ ✓

▪ Quantiferon TB or PPD ✓ ✓ ✓ ✓ ✓

▪ JCV antibody ✓ ✓ ✓ ✓

▪ Serum immunoglobulin panel (IgG, IgM, IgA) ✓ ✓ ✓ ✓ ✓

▪ HIV ✓ ✓ ✓

▪ VZV IgG ✓ ✓ ✓ ✓

2) OTHER

▪ Age appropriate breast cancer screening ✓ ✓ ✓ ✓ ✓

▪ Hereditary breast cancer counseling if + 1st deg relative ✓

▪ Hep B vaccination if no evidence of immunity ✓ ✓

▪ Vaccination against pneumonia ✓ ✓

▪ Vaccination against shingles ✓


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Ocrelizumab (Ocrevus)


1) LABS


▪ Serum immunoglobulin panel ✓ ✓ ✓ ✓ ✓

▪ CD19 B cell monitoring ✓ ✓ ✓

▪ Hep B/C monitoring

2) OTHER

▪ Age-appropriate breast cancer screening ✓ ✓ ✓ ✓ ✓

▪ IVIg supplemental if serum IgG<400 on 2 occasions ✓ ✓

▪ Changing dose or frequency of OCR infusions


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Alemtuzumab (Lemtrada)

• REMS program


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Case 1

• 41 year-old man with history of methamphetamine abuse, diagnosed with RRMS in 2011 when he presented with ambulatory difficulties, with MRI meeting both DIS and DIT criteria.

• Treated with Copaxone 2011 to 2015, stopped for unclear reasons.

• 2016 established care in our clinic with worsening ambulation, EDSS 6, active MRI. JCV ab (-), Quantiferon TB (+)

• Tysabri offered, but due to positive quantiferon TB test (and his reluctance to see ID), started Tecfidera in Dec 2016.

• Relapsed into abuse, with spotty adherence to DMT. Incarcerated.

• Reestablished care in early 2019. JCV ab (-), Quantiferon TB (-) now. – He had been treated for LTBI - he recalls having been tested for TB in 1996, and having

to take a medication for 7-8 months; and his most recent CXR in Feb 2019 is w/o evidence of TB. Cleared by ID to start Tysabri.


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• “Given the poor performance characteristics of tests for LTBI and significant risks of harm associated with LTBI treatment, particularly hepatotoxicity, screening and subsequent treatment should only be performed for patients who are likely to benefit.”


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TB testing and rationale

• DO: Alemtuzumab, Teriflunomide

– TB developed in 2 of >900 ALEM patients (even with mandatory screening in CARE-MS I and recommended screening in CARE-MS II)

• DO NOT (usually): Ocrelizumab

– No TB cases in trials (LTBI+ was exclusion criterion)

– Not used when CD20 used in other diseases

– Screening of those at high risk of TB is recommended:• Recent immigrants

• Diabetes mellitus

• Chronic renal failure


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Case 2

• 56 year-old female with PPMS diagnosed on the basis of progressive leg weakness since 2014, with supportive MRI findings meeting DIS criteria. CSF + OCBs. New lesions noted between 2017 and 2019 on brain MRI. Interested in Ocrevus.– Hep B surface antigen: negative

– Hep B surface antibody: positive

– Hep B core antibody: positive

– HBV PCR negative

– Quantiferon TB and HCV serology negative; VZV IgG immune, normal serum IgG

• Ocrelizumab denied by insurance due to hep B sAb positive status.

• What next?


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• Prophylaxis: with antiviral (e.g. tenofovir)

• Preemptive: monitoring HBV PCR q3mo


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Case 2

• Patient was referred for ID consultation

• Started tenofovir, and then Ocrevus.


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Case 3

• 35 year-old male with RRMS diagnosed based on TM in Nov 2017 (BLE numbness) with supportive MRI findings of DIS with lesions in brain and multiple lesions in spinal cord. DIT met by additional symptoms developing in 2018: imbalance, blurred vision, urinary hesitancy and wrist numbness, and additional lesions on MRI in Sept 2018.

• Treated with generic glatiramer TIW since May 2018, with unsatisfactory response and ongoing accumulation of neurological disability (ataxia/falls, using a cane, debilitating fatigue, urinary hesitancy) + multiple enhancing lesions on MRI in Sept 2018.

• EDSS of 4.0.

• JCV ab (+), Quantiferon TB (-)

• Hep B carrier (HBsAg+, cAb+, sAb-), possibly through vertical transmission.

• Next treatment?


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Case 3 continued

• He started Gilenya, and is having HBV PCR and LFTs q3mo. ID following.

• MRI and symptoms improved.


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Stopping/changing therapy

• Tecfidera– No washout (1, 2, 4)– 0-2 weeks (3)– 4 week washout (5)

• Gilenya– 1 week (2)– 2 wks (1, 3, 4)– 4 wks (5)

• Tysabri– 4 wks (1, 2, 5)– 5-8 wks (3, 4)

• Aubagio washout before (1, 2, 3, 5) or after (4) next DMT


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Closing comments

• Reconsider utility of

– Universal TB screening

– Periodic hep B/C screening on CD20 agents

• Thank you to survey respondents.

• Questions?

vascular surgery common practice headline...headline swedish neuroscience institute program title...

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