Autoimmune Neuromuscular Dis

8/10/2019 Autoimmune Neuromuscular Dis

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Syllabus

Treatment Optimization in AutoimmuneNeuromuscular Diseases

Enduring MaterialRelease: December 18, 2014

Expiration: December 18, 2016


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FacultyChairGil I. Wolfe, MDIrvin & Rosemary Smith Professor and ChairmanDepartment of NeurologyUniversity of Buffalo, State University of New York

FacultyEric Ensrud, MDDirector, Neuromuscular Center, Boston VA Healthcare SystemDirector, Neuromuscular Rehab Clinic, Brigham and Women's Hospital

Carol Lee Koski, MDMedical Director, GBS/CIDP Foundation InternationalProfessor of Neurology (retired), University of Maryland School of Medicine

Target Audience

This educational activity is designed for neurologists, physiatrists, pharmacists and other healthcareprofessionals who practice in the hospital setting with an interest in the management of neuromusculardiseases.

Statement of Need

Patient outcomes can be significantly enhanced with early identification and differential diagnosis ofautoimmune neuromuscular disorders, namely CIPD, GBS, MG, and MMN. This roundtable will feature afaculty-led discussion and a question and answer session highlighting the diagnosis, electrophysiologicaltesting, and treatment of these diseases with IVIG and/or new formulations of SCIG in an effort to provideindividualized treatments and minimize adverse events.

Autoimmune neuromuscular disorders are considered to be a heterogeneous grouping of a number ofdiseases that may be differentiated based on the timing of symptom presentation, pattern ofpresentation/clinical phenotype (ie, symmetrical vs asymmetrical, distal vs proximal, sensory vs motor),EMG pattern, and laboratory chemistries. Differential diagnosis may be challenging as oftentimes thereare only slight nuances that differentiate one disease from another. Clinicians will be introduced toconsensus statements and advances in therapy, as well as new treatment modalities (ie, dosage andtiming) in an effort to enhance recognition, diagnosis, and appropriate treatment selection earlier in thedisease course so as to result in improved patient outcomes.

Learning Objectives

Upon completion of this activity, participants will be able to:

Discuss disease heterogeneity and potential clinical presentations for patients with autoimmuneneuromuscular disorders

Analyze and implement scientific evidence supporting the use of clinical, electrophysiological, andancillary parameters in the diagnosis of autoimmune neuromuscular diseases


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Method of Participation

This activity will take approximately 60 minutes to complete. This broadcast will consist of lectures thatinclude discussion of case studies with collateral slides and a question and answer session.

To receive credit after viewing the online webcast, complete the post-test and evaluation. To receivecredit, 80% must be achieved on the post-test.

A certificate will be immediately available and pharmacist credit will be uploaded to CPE Monitor within 60days of completion. Partial credit may not be awarded for CPE credit; participation in the complete activityis required to receive credit. There is no fee to participate in the activity or for the generation of thecertificate.

Accreditation and Credit Designation

PhysiciansAccreditation Statement

Indiana University School of Medicine is accredited by the Accreditation Council for ContinuingMedical Education to provide continuing medical education for physicians.

Credit DesignationIndiana University School of Medicine designates this enduring material for a maximum of1.0AMA PRACategory 1 Credit(s). Physicians should claim only the credit commensurate with the extent of theirparticipation in the activity.

Note: While it offers CME credits, this activity is not intended to provide extensive training or certificationin the field.

Pharmacists

The Academy for Continued Healthcare Learning is accredited by the Accreditation Council forPharmacy Education as a provider of continuing pharmacy education. This activity has beenapproved for a maximum of 1.0 contact hour.

Activity Type: ApplicationACPE Universal Activity Number (UAN): 0396-0000-14-053-H01-P

Faculty Disclosure Statement

In accordance with the Accreditation Council for Continuing Medical Education (ACCME) Standards forCommercial Support, educational programs sponsored by Indiana University School of Medicine (IUSM)must demonstrate balance, independence, objectivity, and scientific rigor. All faculty, authors, editors,and planning committee members participating in an IUSM-sponsored activity are required to discloseany relevant financial interest or other relationshipwith the manufacturer(s) of any commercialproduct(s) and/or provider(s) of commercial services that are discussed in an educational activity.


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The following faculty financial relationships have been provided:Gil I. Wolfe, MD (Chair)Consulting: Baxter Healthcare Corporation, GrifolsResearch: AlexionSpeaking: Grifols

Eric Ensrud, MD(Faculty)Consulting: Convergence Medical DevicesHonorarium: Osler Institute

Carol Lee Koski, MD(Faculty)Honorarium: Baxter Healthcare Corporation, CSL Behring, Grifols

Disclosure of Unlabeled Use: None

Staff Disclosures

ACHL and Indiana University School of Medicine staff members, and others involved with the planning,development, and review of the content for this activity have no relevant affiliations or financial relationshipsto disclose.

Disclaimer

The content for this activity was developed independently of the commercial supporter. All materials areincluded with permission. The opinions expressed are those of the faculty and are not to be construed asthose of the publisher or grantor.

This educational activity was planned and produced in accordance with the ACCME Essential Areas andElements, Updated Criteria, Policies, and Standards for Commercial Support, as well as the ACPECriteria for Quality and Interpretive Guidelines. Recommendations involving clinical medicine in a

continuing medical education (CME/CE) activity must be based on evidence that is accepted within theprofession of medicine as adequate justification for their indications and contraindications in the care ofpatients. All scientific research referred to, reported, or used in CME/CE in support or justification of apatient care recommendation must conform to the generally accepted standards of experimental design,data collection, and analysis.


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Treatment Optimization in Autoimmune

Neuromuscular Diseases

Our grateful acknowledgement to Baxter Healthcare Corporation and Grifols for educational grants in support of this program..


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Outline

I. Disease Presentation, Diagnosis, and

TherapiesII. Rehabilitation Considerations

III. Q&A


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Case Study

A 24-year old woman awakes one morning with

mild weakness in her legs Throughout the day she notices back pain and a

pins and needles feeling in her feet

The next day, she feels even worse and noticesweakness in her arms

She is admitted to the hospital with suspected

acute inflammatory demyelinatingpolyneuropathy (AIDP) as her history revealed

an influenza infection, 2 weeks prior


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Prodromal Aspects

2/3 of patients report prodromal symptoms

or an event 1 to 4 weeks before onset of

weakness 6-26% gastroenteritis

40-70% upper respiratory infection

Surgery is another eliciting factor

McGrogan A, et al. Neuroepidemiology. 2009;150-163.


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Sensory Loss and Pain

Sensory symptoms and reflexes Sensory loss is usually less prominent than motor involvement

Distribution is usually distal and symmetric; can involvedisruptions in vibration and/or proprioception (JPS) more thansmall fiber functions

Reflexes decreased or absent early in 70% of patients, ankles

>> biceps

Clinically, nearly 1/3 of patients with GBS exhibit normal reflexes,early in the disease course

Pain is prominent; occurs in 89% of patients 50% describe pain as excruciating, distressing, horrible Pain precedes weakness by an average of 6 days

Moulin DE, et al. Neurology. 1997;48:328-331.


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Weakness

Ascending paralysis, maximum at 714 days, does

not worsen after 4 weeks; 50% of maximum at 2weeks, 80% by 3 weeks, >90% by 4 weeks

Weakness is usually symmetric, LE > UE, both

distal and proximal Muscle bulk is relatively well-preserved acutely

At nadir, 30% of patients are tetraplegic, another

30% have only bed mobility

50% have cranial nerve involvement, facial >>

ophthalmoparesis, ptosis


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Autonomic Symptoms

Present in 2/3 of patients

90% have subclinical involvement Sustained sinus tachycardia is most common

Reduction of vagal tone, vagal failure

Secondary to pain

Profound bradycardia, orthostatic hypotension,

hypertension, dry mouth and eyes, GI

dysfunction, urinary retention, diaphoresis


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Respiratory Failure

Significant cause of morbidity and mortality

~ 33% of GBS patients require intubation

Average time to intubation is 7 days after symptom

onset

What are the early indicators of subsequentprogression to respiratory failure? Vital capacity (VC)


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Variants in Presentation

Acute Inflammatory Demyelinating

Polyneuropathy (AIDP)

Acute Motor Axonal Neuropathy (AMAN)

Acute Motor and Sensory Axonal Neuropathy

(AMSAN)

Miller Fisher Syndrome


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Prognostic factors Category Score

Age 40 0

(years) 41 - 60 1

> 60 2

Diarrhoea absent 0(4 weeks) present 1

MRC sumscore 51 - 60 0

(1 week) 41 - 50 3

31 - 40 6

0 - 30 9

mEGOS 0 - 12

Modified Erasmus GBS outcome score

(mEGOS)

Good prognosis

Percentage not being able to

walk unaided after 4 weeksAUC = 0.87

Modification: MRC sumscore at 1 week and outcome after 4 weeks

Erasmus GBS Outcome Score

Modified from van Koningsveld R, et al.Lancet Neurol. 2007;6:589-594.


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GBS patients with

higher increments in

serum IgG 2 weeks

after dosing (groups 3

& 4) had a better

outcome reflected inwalking unaided Group numbers refer to

quartiles of IgG increment in

IgG level from baseline to 2

weeks after treatment.

Group 4 outcome is highest

Kuitwaard K, et al.Ann Neurol. 2009;66:597-603.

IgG Levels and Outcome


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PE vs IVIG vs Combination Treatment

Comparison of IVIG, PE, and a combined

regimen in adult patients with severe GBS (aidneeded for walking)

Multiple outcome measures including need for

and length of, artificial ventilation, days tounaided walking, hospital discharge and return

to work, number unable to walk after 48 weeks,

and deaths

Patients were followed for 48 weeks

Hughes RAC, et al. Lancet. 1997;349:225-230.


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PE vs IVIG vs Combination Treatment

(contd)

Major inclusion criterion

Patients had to have had an onset of neuropathicsymptoms within the past 14 days

Dosing

PE: five, 50 mL/kg exchanges over 813 days

IVIG: 0.4 g/kg daily for 5 days

Combination: PE course followed by IVIG course



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Outcome Measures

PE IVIG PE

+ IVIG

Mean(SD)change

indisability after4

weeks

0.9(1.3) 0.8 (1.3) 1.1(1.4)

No.ventilatedafter

randomization 28(23.1%) 29(22.3%) 21(16.4%)

Median daysto

stopartif.

ventilation*

29(1457) 26(1545) 18(1056)

Mediandaystounaidedwalking*

49(19148) 51(20164) 40(19137)

Mediandaysto

hospitaldischarge* 63(28124) 53(21135) 51(24117)

Mediandaysto

returnto

work*

290(122>400) 371(129>400) 281(96>400)

Number unableto

walkunaidedafter

48weeks

19(16.7%) 21(16.5%) 17(13.7%)

Deaths 5(4.1%) 6(4.6%) 8(6.3%)


*IQR=interquartile range

Missing for 7 patients in PE,1 in IVIG,and 6 in Combination group


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Takeaways

The authors determined that PE and IVIG had similar

efficacies and that combination treatment did not confer

an added advantage.1

AAN Guidelines2

PE recommended for

Nonambulatory patients within 4 weeks of onset ofneuropathic symptoms (LOE=A, COR=II)

Ambulatory patients within 2 weeks of onset of neuropathic

symptoms (LOE=B, COR=limited class II)

If started within 2 weeks, there are equivalent effects of PEand IVIG in patients requiring walking aids (LOE=B, COR=I)


AAN Guideline Summary for Clinicians. Immunotherapy for

Guillian-Barr Syndrome. Available at

http://tools.aan.com/professionals/practice/pdfs/gbs_guide_aan_mem.pdf*LOE=level of evidence; COR=class of recommendation


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Case Study

A 45-year old man has noticed progressive

weakness in his arms and legs over the past 8weeks. It has become more difficult to carry on

with normal activities and he tires quickly

He has a desk job but even the short commuteto the office in his car is cumbersome as he

describes his movements as heavy and has a

constant feeling of having to drag his feet

He has also noticed decreased sensitivity to

touch in his right hand and some difficulty getting

out of a chair without using his arms


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Diagnostic Criteria of Classic CIDP No universally accepted diagnostic criteria15

No biomarker1

CIDP = chronic inflammatory demyelinating polyneuropathy; CSF = cerebrospinal fluid; MRI = magnetic resonance

imaging

1. Koski CL, et al. J Neurol Sci. 2009;277:1-8. 2. Hughes RAC, et al. Eur J Neurol. 2006;13:326-332.3. Saperstein DS, et al. Muscle Nerve 2001;24:311-324. 4. Saperstein DS, Barohn RJ. Curr Neurol Neurosci Rep.

2003;3:57-63. 5. Berger AR, et al. J Peripher Nerv Syst. 2003;8:282-284.

1 Clinical Motor/sensory impairment

Disease duration/progression (8 weeks)

Hyporeflexia/areflexia

2 Electrophysiology

Evidence for demyelination

3 CSF analysis

4 Nerve biopsy

5 Additional potentially supportive evidence MRI

Response to immunomodulatory treatment

Mandatory

Not mandatory


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Electrodiagnostic Criteria for CIDP

Practical concepts Slower than expected for level of axonal loss: >25%

(125% of ULN of DL, Fwaves)

Evidence of primary demyelination (temporal

dispersion, conduction block)

Image courtesy of Mark B. Bromberg, MD, PhD.


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CIDP Electrophysiology

Complex topic

Need to study multiple nerves, MS of PNS

Correct temperature (>32.00

C) is crucial NCS shows electrophysiologic evidence of demyelination

Distal motor latency >125% normal

Conduction velocity


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CIDP Diagnosis:

Proposed 2009 Criteria

Patients with a chronic polyneuropathy, progressive for at least 8

weeks would be classified as having CIDP if: No serum paraprotein and No documented genetic abnormality

AND EITHER

a) At least 75% of motor nerves tested had a recordable response

AND one of the following:

> 50% of motor nerves tested had an abnormal DL or

>50% of motor nerves tested had an abnormal CV or

>50% of motor nerves had an abnormal F-latency

OR

b) Symmetric onset or symmetric exam, and

Weakness in all four limbs and

At least one limb with proximal weakness


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CIDP and Variants

Chronic autoimmune demyelinating polyneuropathy

AtypicalCIDP

Non-CIDP

DADS

MADSAM

LewisSumner

Pure

Sensoryincl ataxic Pure Motor Focal

MMNParaprotein/

MGUS

DADS = distal acquired demyelinating symmetric neuropathy; MADSAM = multifocal acquired demyelinating

sensory and motor neuropathy; MGUS = monoclonal gammopathy of unknown significance; MMN =

multifocal motor neuropathy.

Koski CL, et al. J Neurol Sci. 2009;277:1-8. Hughes RAC, et al. Eur J Neurol. 2006;13:326-332. Kller H, etal. N Engl J Med. 2005;352:1343-1356.

TypicalCIDP


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Corticosteroids1

IVIG*, 1-3

Plasma exchange1-2,4

1. Van den Bergh PYK, et al. Eur J Neurol. 2010;17(3):356-363. 2. Van den Burgh PYK, Rajabally YA.Presse Med. 2013;42(6 pt 2):e203-e215. 3. Hughes RAC, et al. Lancet Neurol. 2008;7(2):136-144. 4.

Gorson KC. Ther Adv Neurol Disord. 2012;5(6):359-373.

Treatments of CIDP Supported

by Randomized Controlled Trials

*ONLY FDA INDICATION


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CIDP: EFNS/PNS Recommendations

for TreatmentInductionofTreatment

Sensory

and

Motor

CIDP

IVIGorcorticosteroid

(Choicebasedoncontraindications)

Pure

Motor

CIDP

IVIG

Inadequate

Response

Considercombination/additionaltherapies

If

Ineffective

ConsiderPE

If Effective

Maintenance therapy to

achieve maximal

response

Reduce to lowesteffective dose

Hughes RAC, et al. Eur J Neurol. 2006;13(4):326-332.


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IgG Responsiveness

Not all patients with CIDP respond to IVIG

Factors contributing to lack of response include:

- Disease Factors

Time between symptom onset and diagnosis and treatment

Extent of axonal damage/loss

Reduced CMAP

Muscle atrophy

Treatment Response

Linked in the Japanese population to polymorphisms in TAG-1

Iijima M, et al. Neurology. 2005;64:1471-1475.


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Time to Response in Patients Who

Responded to IVIG

IGIV-C = immune globulin intravenous, 10% caprylate/chromatography

purified; INCAT = Inflammatory Neuropathy Cause and Treatment

0%

20%

40%

60%

80%

100%

41%

Week 3 (n=14)Day 16 (n=13)

IGIV-C Subjects (n=32)

Week 6 (n=30)

44%

94%

Cumulative Response Among IGIV-C Subjects who Improvedby 1 Point (Adjusted INCAT by Week 24), First Period

Latov N, et al.Ann Neurol. 2008;64(suppl 12):S8. Abstract M-18.


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Patients Receiving IVIG Continued to

Improve and Maintained Improvement

Patients in this analysis received IVIG in the first period/crossover period and in the extension phase.

INCAT = inflammatory neuropathy cause and treatment

IVIG (n=27)

0.0

-0.5

-1.0

-1.5

-2.0

-2.5

0 4 8 12 16 20 24 28 32 36 40 44 48

Week

Change

FromB

aselin

ein

AdjustedINCATSco

re

Latov N, et al.Ann Neurol. 2008;64(suppl 12):S8. Abstract M-18.


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Average Time Between Symptom Onset and

Treatment Compared to Current Disease Activity

0

0.5

1

1.5

2

2.5

Activedisease

Remissionwith

disability

Remission

without

disability

0 40 60

Percent able to

withdraw from

therapy

20% of patients who responded to thesurvey were able to withdraw from

therapy (and who were diagnosed

with CIDP;166 out of 858

respondents)

GBS/CIDP FI Survey.

*T test for equality of means

between Active and In

remission p


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Right Foot

Left Foot

Typical Pharmacokinetic

Curve of IVIG

IVIGInfusion

Bonilla FA. Immunol Allergy Clin North Am. 2008;28:803-819; Pollard J, Armati

PJ. J Peripher Nerv Syst. 2011;16:15-23; Dalakas MC. Neurology.1994;44;223-226.

IVIGInfusion

Direct Relationship Between IgG Dosing and

Patient Response: PK of IVIG in a CIDP Patient


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0 10 20 30 40 50 60 70

Rajabally (1)

Broyles(2)

Kuitwaard (3)

1. Rajabally YA, et al. J Neurol. 2013;260:2052-2060. 2. Broyles R, et al.

Postgrad Med. 2013;125:65-72.3. Kuitwaard K, et al. J Neurol Neurosurg Psychiatry. 2013;84: 859-861.

(47 % 21 Days)

Optimized, Individual Therapy May Require More

Frequent Dosing Than Monthly Intervals

Percent of Patients Receiving IVIG at Intervals 15 Days


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SCIG in CIDP

A randomized, double-blinded, placebo controlled

trial of the effect of SCIG on muscular

performance in CIDP

Dynamometry x1 x3x2 x4

SCIG

SCNaCl

44 4

IVIG

IVIG

Twice or thrice weeekly infusions

Twice or thrice weeekly infusions

2Timeinweeks

Screening for

eligibility andselection

muscles for

dynamometry

RANDOMIZATION

N=30

Jakobsen J, et al. Aarhus University Copenhagen. AAN 2012.

R d i d D bl bli d Pl b ll d


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-40

-30

-20

-10

0

10

20

MRC 40-MWT 9-HPTGS

SCIG Placebo

***

Improvem

entofperform

ance(%)

X1 X2 X3 X4

10

15

20

25

SCIG Placebo

* *

Plasma-

ImmunoglobulinG

(g/L)

MRC scale; GS-grip strength; 40-mWT-40 meter walking test; 9-HPT-9 hole peg test

X1 and 2=IVIG; X3 and 4=SCIgG or saline

Treatment with subcutaneous immunoglobulin (SCIG) in CIDP is feasible, safe

and effective. SCIG improves muscle strength, walking performance and

disability score as compared to placebo treatment.

Note: SCIG not approved for patients with CIDP, in the US

Randomized, Double-blind, Placebo-controlled

Trial of SCIG in 30 Patients with CIDP

Jakobsen J, et al. Aarhus University Copenhagen. AAN 2012.

IVIG IV M h l d i l f CIDP


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IVIG vs IV Methylprednisolone for CIDP

A Randomized Controlled Trial: Methods A multicenter, randomized, double-blind, placebo controlled, parallel-

group study in patients with CIDP

Assessed efficacy and tolerability of IVIG (0.5 g/kg per day for 4 days)

and IV methylprednisolone (0.5 g in 250 mL sodium chloride solution per

day for 4 days)

Each month, for six months

After therapy discontinuation, patients were followed up for 6 months to

assess relapses

Nobile-Orazio E, et al. Lancet Neurol. 2012;11(6):493-502.

IVIG IV M th l d i l f CIDP


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A Randomized Controlled Trial: Findings 45 patients (24 IVIG, 21 MPIV)

11 of 21 (52%) on MPIV compared to 3 of 24 (13%) on IVIG

stopped drug due to lack of efficacy (8/MP and 3/IVIG), AE (1MP) or voluntary withdrawal (2/MP)

After discontinuation of Rx more patients on IVIG worsened

38% (8/21) than those on MP (none of ten)



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A Randomized Controlled Trial: Conclusions

Long-term use of IVIG was less frequently discontinued

because of inefficacy, AE, or intolerance than was treatment

with MPIV Methylprednisolone induced a longer-term remission than did

IVIG

Whether the latter difference might also affect the chroniccourse of the disease remains to be clarified


Ti t Cli i l D t i ti Aft


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Time to Clinical Deterioration After

Therapy Discontinuation

Nobile-Orazio E, et al. J Neurol Neurosurg Psychiatry. 2014;Sep 22. doi: 10.1136/jnnp-2013-307515.


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CIDP Long Term Prognosis

1. Response rate to each of three primary treatments

(IVIG, CS, and PlEx) is similar and varies from 60-

70%1,2

2. Although IVIG results in a more rapid response, itis more likely to lead to long term dependence as

opposed to remission with use ofcorticosteroids1,2,3

3. Earlier treatment within 5-6 mos of symptom onsetreduces chronic disability and improves the chanceof drug free remission1,2

1. Viala K, et al. J Peripher Nerv Syst. 2010;15:50-56.

2. Querol K, et al. Muscle Nerve. 2013;48:870-876.

3. Nobile-Orazio E, et al. J Neurol Neurosurg Psychiatry. 2014;Sep 22. doi:

10.1136/jnnp-2013-307515.


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Electrophysiology in MMN diagnosis

MMN patients have a focal block ofmotor nerve conduction along thecourse of motor nerves rather than at

other than entrapment sites

Conduction block is variably definedas a 50% reduction in the CMAPamplitude

Sensory conduction overcorresponding nerve segments isnormal

Conduction block may go undetectedunless multiple segments includingproximal regions in several nerves aretested.

www.cidpusa.org/multifocal_motor_neuropathy.htm

MMNwaveforms

M.Bromberg


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Differential Diagnosis of MMN

Features MMN CIDP ALS

Lowermotorneuronweakness Distal,asymmetrical Distalandproximal,

symmetrical Asymmetrical

Uppermotorneuronsigns Absent Absent Present

Sensoryloss Absent Usuallypresent Absent

ConductionBlock >90% Frequent Absent

Sensoryconduction NormalSNAP LowtoabsentSNAPorNormal NormalSNAP

Cerebrospinalfluidprotein Normal ElevatedproteinincreasingwithtimeorNormal

Normal

AntiGM1antibodies 6080% Rare Rare

NCS = nerve

conduction study

Chart adapted from : Bosch, EP and Smith, B E. Disorders of

Peripheral Nerves. In Neurology in Clinical Practice, 2nd ed., ed.W.G. Bradley et al., 2091. 2000 Boston: Butterworth-Heinemann.

SNAP = sensory

nerve action potential


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IVIG Trial Results in MMN

Co-primary endpoints: Grip strength in the more affected hand

Disability Scale (measures the patient's ability to perform daily tasks such as

zippering, buttoning, washing and feeding).

Results: During infusion treatment, the difference in relative change in mean grip strength in

the more affected hand was 22.94% compared to placebo.

A greater proportion of patients who received placebo experienced deterioration

compared to those receiving IVIG (35.7% vs.11.9%, respectively).

Differences in the outcomes of the co-primary endpoints were statistically significant.

In addition, the 69% of patients during the placebo period required an accelerated

switch to IVIG due to functional deterioration during the placebo period.

Adverse Events (>5% of subjects): The only serious adverse reaction was a pulmonary embolism which was judged tobe treatment-related. Of note, IVIG is known to carry a thrombotic risk. No deaths or

unexpected serious adverse events related to study product occurred.

http://www.marketwatch.com/story/baxter-announces-fda-approval-for-gammagard-liquid-as-a-treatment-for-multifocal-motor-neuropathy-2012-06-25.


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Subcutaneous IgG in MMN Randomized, blinded cross-over comparing IVIG and SCIG of 9 patients IGSC was given 2 to 3 times weekly at 4-8 sites (max 20 ml/site; 16% IGSC

product)

CONCLUSION: IVIG and SCIG are equivalent in the short-term with respect tofunction and quality of life

Two-year follow up of 6 IVIG responsive patients (including 5 of the previous

study) while on SC showed no changes in impairment and disability scores 4 patients required increased dosing over time

CONCLUSION: SCIG able to maintain MMN function over 2 years

Note that in the US, SCIG is only approved for primary humoral immunodeficiency

and not any other diseases or disorders at this time

Harbo T, et al. Eur J Neurol. 2009;16:631-638.Harbo T, et al. Neurology. 2010;75:1377-1380.

Subcutaneous Immunoglobulin Therapy


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Subcutaneous Immunoglobulin Therapy

for MMN

Eftimov F, et al. J Peripher Nerv Syst. 2009;14:93-100.

Summary


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Summary

Diagnosing Neuromuscular Disease

We have reviewed three disorders of theneuromuscular system that cause weakness,

including GBS, CIDP, and MMN

Diagnosis of individual cases required analysis of

features of the history and physical as well aslaboratory findings

Electrophysiological testing and interpretation are

pivotal to the diagnosis of disorders that in manycases have no known specific diagnostic test or

biological marker

O tli


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Outline


Therapies

II. Rehabilitation Considerations

III. Q&A

R h bilit ti i CIDP


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Rehabilitation in CIDP

Patients with CIDP experienced 20% less

fatigue after a 12 week program of bicycleexercise training -3x/week, 40 min duration, at 60% VO2 Max (~able to

hold conversation while riding)

Garssen MPJ, et al. Neurology. 2004;68:2393-2395.

R h bilit ti i GBS


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Rehabilitation in GBS

High intensity (1 hr, 3x/week) physical rehab program

over 12 weeks was associated with a significant

reduction in disability and a significant increase infunction (FIM scores improved 68% vs. 32%) when

compared with low-intensity (30 min 2x/week) program

Muscle strength recovery with physical rehab after GBS

continued to improve at 18 months after onset of

symptoms, underscoring the need for long-term rehab

for at least for a year and a half or longer

Khan F, et al. J Rehab Med. 2011;43:638-646.El Mhandi L, et al.Am J Phys Med Rehab. 2007;86(9):712-724.

Rehabilitation in MMN


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Rehabilitation in MMN

Patients with MMN experience decreased daily

functioning from decreased muscle strength,

decreased dexterity, and fatigue, similar to other

neuromuscular diseases.

Decreased fatigue may be amenable to

intervention.

The use of hand aids may increase hand

dexterity and autonomy and the use of walking

aids may increase walking ability and autonomy.

Erdmann PG, et al. J Periph Nerv Syst. 2010;15:113-119.

Outline


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Outline


Therapies

II. Rehabilitation Considerations

III. Q&A

Documents

Autoimmune Neuromuscular Dis