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
Download Presentation The PPT/PDF document "Perspectives on Best Practices for Manag..." is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
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.