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Perspectives on Best Practices for Managing Acute Relapses Perspectives on Best Practices for Managing Acute Relapses

Perspectives on Best Practices for Managing Acute Relapses - PowerPoint Presentation

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Perspectives on Best Practices for Managing Acute Relapses - PPT Presentation

in Multiple Sclerosis Moderator Barry G Arnason MD Professor of Neurology University of Chicago S taff Physician Department of Neurology University of Chicago Hospitals and ID: 385449

neurol relapse sclerosis multiple relapse neurol multiple sclerosis treatment patients 2012 acute steroids sci 2013 patient therapy medical oral

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Slide1

Perspectives on Best Practices for Managing Acute Relapses in Multiple Sclerosis

Moderator

Barry G. Arnason, MD

Professor

of

Neurology

University

of

Chicago

S

taff Physician

Department

of

Neurology

University

of Chicago Hospitals and

Clinics

Chicago, Illinois Slide2

PanelistsKathleen Costello, RN, MS, CRNP, MSCN

Assistant Professor

Johns Hopkins Medical InstitutionsNurse PractitionerJohns Hopkins HospitalBaltimore, Maryland

Saud A. Sadiq, MD

Director

and Senior Research

Scientist

Tisch

Multiple Sclerosis Research Center of New

York

Director

International

Multiple Sclerosis Management

Practice

New York, New YorkSlide3

DisclaimerThis program will include discussion of treatment options that may deviate from F

DA recommendations

. Slide4

Program GoalsDiscuss

therapeutic options available to manage acute relapses in patients with

MSIndividualize therapy for acute relapse in MSDevelop strategies for managing suboptimal response to acute relapse treatment and addressing patient tolerability issuesSlide5

OverviewChallenge of MS relapse

Underlying

pathophysiologyStrategies for managing relapseSlide6

Definition of RelapseIn clinical trials:Neurological deficit lasting > 24-48 hours

With or without change in EDSS score

In the clinic:Change from baselineSustained for a period of time (hours, days)Otherwise unexplained by other medical conditionsRelapse is not usually a medical emergencySymptoms may resolve over time

Vollmer T.

J

Neurol

Sci.

2007;256:S5-S13.

[1]Slide7

Relapse Triggers and Associated Conditions: Cause or Effect?Infectiona

Fever can worsen MS symptoms

Demyelinated nerves are sensitive to temperature changesInfection can precipitate MS attacksOther conditions (pseudorelapse)DepressionStress

Sleep issues

Fatigue

Heat intolerance

Headaches

b

a

. Vollmer T.

J

Neurol

Sci.

2007;256:S5-S13.

[1]

b

.

Mohrke

J, et al.

PLoS

One. 2013;8:e69570.

[2]Slide8

Patient AssessmentResponse to relapse is highly

individualized

Symptoms may resolve on their own (pseudorelapse)Encourage patients to call to discuss the situationTake a careful historyMRI may not be necessaryConsider bringing patient in for clinical evaluation (especially if motor symptoms are involved)

In spinal cord disease, MRI is not likely to be negativeSlide9

Relapse Treatment: ParadigmTreatment may be indicated if:Patient reports new neurological symptoms and change in function affecting quality of life

S

ensory, cognitive, mood, or motorAssociated medical conditions have been ruled outMRI shows Gd-enhancing lesion(s)Acute relapse is not likely present if during routine evaluation, MRI in an asymptomatic patient shows new lesion(s) or a Gd-enhancing lesion since last MRIIn such cases, consider changing DMT

Myhr

KM, et al.

Acta

Neurol

Scand

Suppl.

2009;73-80.

[4]Slide10

Relapse Treatment: SteroidsSteroids: first-line treatmenta,b

Standard regimen

= 1 g/d for 3-5 daysTreatment for other autoimmune diseases usually involves lower doses (eg, 5-40 mg/d for RA)Steroid mechanismcAt low doses, steroids regulate gene activityAt high doses, steroids affect cell membranes (ie, not underlying disease mechanisms)

a

. Burton JM, et al.

Cochrane Database

Syst

Rev.

2012;12:CD006921.

[3]

b

.

Myhr

KM, et al.

Acta

Neurol

Scand

Suppl.

2009;73-80.

[4

]

c

. Arnason BG, et al.

Mult

Scler

.

2013;130-136.

[11]Slide11

Relapse Treatment: ApproachesDr SadiqFor most patients with relapse:

1 g/d

IVMP x 3 days for most patients with relapseOral taper not necessaryIf motor symptoms present, consider:5 daysOral taper (usually rapid, 2-3 weeks)Address steroid adverse effects, eg:Sleep issues

Gastrointestinal upsetSlide12

Ms CostelloHigh-dose oral prednisone (eg, 1250 mg) an option Good efficacy; minimal adverse effectsa

Some patients experience sleeplessness, may not feel as well

IV steroidsProtocol at Johns Hopkins = IVMP 1 g/d x 5 days or oral equivalentChart review (N = 50) did not identify a difference in outcomes with 5 days vs 3 daysba. Morrow SA, et al. Can J Neurol Sci. 2012;39:352-354.

[5]

b. K. Costello, written communication, September 2013.

Relapse Treatment: Approaches (

cont

)Slide13

Steroid Treatment: Risks and BenefitsVariable patient response

Some patients feel energetic; others feel jittery, sleepless

Adverse effects can occur and should be managedCommon AEs: Flushing, acne, dyspepsia, metallic tasteSevere AEs: avascular necrosis, osteoporosis, hypertension, glucose intolerancea-cGoal: Accelerated recovery; restore function in short termSteroids per se do

not delay disease

progression

d

…But treating acute relapse and optimizing ongoing therapy may affect progression

Frequent

use (pulsing) should

be avoided

Consider switching DMT

a. Sahraian MA, et al.

Neurol Sci.

2012;33:1443-1446.

[6]

; b. Ce P, et al.

Eur J Neurol.

2006;13:857-861.

[7]

;

c. Ciccone A, et al.

Cochrane Database Syst Rev.

2008:CD006264.

[8]

;

d. Andersson PB, et al.

J Neurol Sci.

1998;160:16-25.

[9]Slide14

ACTHa. Arnason BG, et al. Mult Scler.

2013;19:130-136.

[11]; b. Catania A. J Leukoc Biol. 2007;81:383-392.[12]Only FDA-approved drug for managing acute MS attacksInduces production of glucocorticoids, mineralocorticoids

Binds to 5 different melanocortin receptors

(1 of which regulates

steroids)

a,bSlide15

ACTH (cont)Option for selected patients

Intolerant to IVMP

History of response to ACTHDrawbacksCost, insurance barriersAdverse effects related to increase in steroids (eg, bloating, anxiety, appetite changesa)Advantages

Bone-sparing (avoids osteoporosis; aseptic

necrosis

b

)

a. H. P. Acthar Gel (repository corticotropin injection) [package insert].

[15]

b. Arnason BG, et al.

Mult Scler.

2013;19:130-136.

[11

]

Slide16

Other Options for Managing RelapsePlasma exchange (plasmapheresis)

Often used in transverse myelitis, NMO

aConsider for patients with spinal cord disease who are still plegic after initial steroid therapyTypical regimen: 5 exchanges over 10 daysPotential risk of infected linesIVIGOption for pregnant patients reluctant to use steroidsMay provide more complete recovery in optic neuritis compared

with steroids

b

a

. Bonnan M,

Cabre P.

Mult Scler Int.

2012;2012:787630.

[14]

b. Magraner MJ, et al.

Neurologia.

2013;28:65-72.

[15]

Slide17

Comprehensive MS Management Relapse provides opportunity to reassess patients,

review treatment strategy, and make adjustments as needed

Evaluate and treat symptoms (eg, mood, fatigue, functional loss)A team approach is valuablePhysical therapyOccupational therapySpeech therapyTreat the

whole patientSlide18

Adjusting MS TreatmentAcute relapse may be a signal that treatment is not optimal

Has the DMT had time to work?

Are other medical conditions involved (eg, cancer, heart disease)?Is a switch in DMT indicated?Slide19

Summary and Key PointsHigh-dose steroids (IVMP, oral prednisone) are standard treatments for MS relapse

Other options include ACTH,

plasma exchange, IVIGOveruse of steroids may cause serious adverse effectsManage the whole patient, not just the immediate symptom Assess and address other medical issues (eg, depression, headache)Slide20

AbbreviationsACTH = adrenocorticotropic hormone AE = adverse eventDMT = disease-modifying therapyEDSS = Expanded Disability Status Score

FDA = US Food and Drug Administration

IV = intravenousIVIG = intravenous immunoglobulin GIVMP = intravenous methylprednisoloneMRI = magnetic resonance imagingMS = multiple sclerosisNMO = neuromyelitis opticaRA = rheumatoid arthritisRRMS = relapsing-remitting multiple sclerosisSlide21

References1. Vollmer T. The natural history of relapses in multiple sclerosis. J Neurol Sci.

2007;256

Suppl 1:S5-13.2. Möhrke J, Kropp P, Zettl UK. Headaches in multiple sclerosis might imply an inflammatorial process. PLoS One. 2013;8:e69570. 3. Burton JM, O'Connor P, Hohol M, Beyene

J. Oral versus intravenous steroids for treatment of relapses in multiple sclerosis.

Cochrane Database

Syst

Rev.

2012;12:CD006921.

4

.

Myhr

KM,

Mellgren

SI. Corticosteroids in the treatment of multiple sclerosis.

Acta

Neurol

Scand

Suppl.

2009;73-80.

5

. Morrow SA, McEwan L,

Alikhani

K,

Kremenschutzky

M. MS patients report excellent compliance with oral prednisone for acute relapses.

Can J

Neurol

Sci.

2012;39:352-354

.

6.

Sahraian

MA,

Yadegari

S,

Azarpajouh

R,

Forughipour

M. Avascular necrosis of the femoral head in multiple sclerosis: a report of five patients.

Neurol

Sci.

2012;33:1443-1446.Slide22

References (cont)7. Ce P,

Gedizlioglu

M, Gelal F, Coban P, Ozbek G. Avascular necrosis of the bones: an overlooked complication of pulse steroid treatment of multiple sclerosis. Eur J Neurol. 2006;13:857-861.8. Ciccone A, Beretta S, Brusaferri F, Galea I, Protti A, Spreafico

C. Corticosteroids for the long-term treatment in multiple sclerosis.

Cochrane Database

Syst

Rev.

2008:CD006264.

9

.

Andersson

PB,

Goodkin

DE.

Glucocorticosteroid therapy for multiple sclerosis: a critical review.

J

Neurol

Sci.

1998;160:16-25.

10

. Glaser GH, Merritt HH. Effects of ACTH and cortisone in multiple sclerosis.

Trans Am

Neurol

Assoc.

1951;56:130-133.

11

.

Arnason

BG,

Berkovich

R, Catania A,

Lisak

RP,

Zaidi

M. Mechanisms of action of adrenocorticotropic hormone and other

melanocortins

relevant to the clinical management of patients with multiple sclerosis.

Mult

Scler

.

2013;19:130-136.

12

. Catania A. The

melanocortin

system in leukocyte biology.

J

Leukoc

Biol.

2007;81:383-392

.Slide23

References (cont)13. H. P. Acthar Gel (repository

corticotropin

injection) [package insert]. Hayward, CA: Questcor Pharmaceuticals, Inc; 2012.14. Bonnan M, Cabre P. Plasma exchange in severe attacks of neuromyelitis optica. Mult Scler Int. 2012;2012:787630.

15

.

Magraner

MJ,

Coret

F, Casanova B. The effect of intravenous immunoglobulin on

neuromyelitis

optica

.

Neurologia

. 2013;28:65-72.