Medical and Surgical Medical and Surgical Management of MGManagement of MG

Brian A. Crum, MDBrian A. Crum, MD

Department of NeurologyDepartment of Neurology

Mayo ClinicMayo Clinic

Rochester, MNRochester, MN

MGFA National Meeting, St. LouisMGFA National Meeting, St. Louis

May, 2010May, 2010

Basic FactsBasic Facts Prevalence 20 in 100,000Prevalence 20 in 100,000 Women: younger (30’s); Men: older (40’s)Women: younger (30’s); Men: older (40’s) The disease looks different in different peopleThe disease looks different in different people The disease is treatableThe disease is treatable Most patients improve and do well Most patients improve and do well The disease is most active the first few yearsThe disease is most active the first few years There are significant costs, side effects, and There are significant costs, side effects, and

manifestations of the diseasemanifestations of the disease

Variables in TreatmentVariables in Treatment

Ocular vs. Generalized vs. CrisisOcular vs. Generalized vs. Crisis Types of antibodies (AchR vs. MuSK)Types of antibodies (AchR vs. MuSK) Thymoma or notThymoma or not Age and other medical conditionsAge and other medical conditions Men vs Women (esp childbearing)Men vs Women (esp childbearing) Access to healthcare Access to healthcare

Not: Levels of antibodies in the bloodNot: Levels of antibodies in the blood

Ocular vs. Ocular vs. GeneralizedGeneralized

Ocular: Just in the eyesOcular: Just in the eyes Generalized: Face, arms, legs, neckGeneralized: Face, arms, legs, neck

80+% of MG starts in the eyes80+% of MG starts in the eyes Many will ‘generalize’ in the first months-Many will ‘generalize’ in the first months-

yearyear Most that DON’T generalize at a year will Most that DON’T generalize at a year will

remain ocularremain ocular

Ocular vs. GeneralizedOcular vs. Generalized

Treatment is mostly symptomaticTreatment is mostly symptomatic If double vision and droopy eyes are a If double vision and droopy eyes are a

problem, need treatmentproblem, need treatment

Treatment with steroids Treatment with steroids maymay reduce the reduce the chance of ‘generalizing’chance of ‘generalizing’

Thymectomy generally not recommended Thymectomy generally not recommended for just ocular diseasefor just ocular disease

Types of AntibodiesTypes of Antibodies

MuSK antibody positive MGMuSK antibody positive MG Affects face, neck, shoulders, breathingAffects face, neck, shoulders, breathing Tests (like EMG) may not show as much of Tests (like EMG) may not show as much of

the MG changesthe MG changes AchR antibodies are negativeAchR antibodies are negative Mestinon/pyridostigmine less effective, may Mestinon/pyridostigmine less effective, may

make weakness worsemake weakness worse Plasma Exchange worksPlasma Exchange works Thymectomy probably notThymectomy probably not

Thymoma or NotThymoma or Not

10-20% of MG patients have a thymoma10-20% of MG patients have a thymoma Most have no symptoms (other than MG)Most have no symptoms (other than MG) Found with imaging like CTFound with imaging like CT Surgery is done to remove tumorSurgery is done to remove tumor

Usually totally removedUsually totally removed If not, chemo or radiation done w/ oncologistIf not, chemo or radiation done w/ oncologist

MG is more difficult to treatMG is more difficult to treat

Overview--TreatmentsOverview--Treatments Short TermShort Term

Symptomatic: MestinonSymptomatic: Mestinon Immune-mediating: IVIG, Plasma ExchangeImmune-mediating: IVIG, Plasma Exchange

Medium TermMedium Term Immune-Mediating: SteroidsImmune-Mediating: Steroids

Long TermLong Term Immune-Mediating: SeveralImmune-Mediating: Several

Longer TermLonger Term ThymectomyThymectomy

Goal: Normalize strength, minimal medications (or none)Goal: Normalize strength, minimal medications (or none)

Mestinon (pyridostigmine)Mestinon (pyridostigmine) Short-actingShort-acting

30-60 minutes to start working, lasts a few hours30-60 minutes to start working, lasts a few hours Used ‘as needed’Used ‘as needed’ Patients can experiment with dosesPatients can experiment with doses

½ to 1 to 2 pills at a time½ to 1 to 2 pills at a time 3-6 times a day3-6 times a day

Too much can lead to cramps, twitching, Too much can lead to cramps, twitching, diarrhea, sweating, more weaknessdiarrhea, sweating, more weakness

Also a longer-acting form (at night)Also a longer-acting form (at night)

Muscle Contraction

NeuroMuscular

Transmission

Acetylcholine

Ach Esterase

Ach receptor

Short-Term: IVIG/Plasma Short-Term: IVIG/Plasma ExchangeExchange

Usually for severe weakness (ie in the Usually for severe weakness (ie in the hospital)hospital)

One not better than the other (in studies One not better than the other (in studies on crisis)on crisis)

IVIG shown to be effective in improving IVIG shown to be effective in improving weakness and reducing need for steroids weakness and reducing need for steroids in outpatients with MGin outpatients with MG

IVIGIVIG

3-5 days in a row3-5 days in a row Pooled antibodies from blood donorsPooled antibodies from blood donors

Screened for transmissible diseaseScreened for transmissible disease Thought to reduce the immune attack on Thought to reduce the immune attack on

musclemuscle Improvement w/in daysImprovement w/in days Requires and IV in the armRequires and IV in the arm Expensive, but typically coveredExpensive, but typically covered Done more in outpatient setting nowDone more in outpatient setting now

Plasma ExchangePlasma Exchange

““Filtering” of blood through a Filtering” of blood through a machinemachine

Typically done every other day for 5-7 Typically done every other day for 5-7 exchanges (10-14 days)exchanges (10-14 days)

May required a larger IV line (central line) May required a larger IV line (central line) placed in neck or chestplaced in neck or chest Risks of infection or blood clottingRisks of infection or blood clotting

Improvement in daysImprovement in days Usually reserved for hospital patientsUsually reserved for hospital patients

Medium-TermMedium-Term

Prednisone (the ‘love/hate’ drug)Prednisone (the ‘love/hate’ drug) Proven to work in MGProven to work in MG Takes days to weeks to see improvementTakes days to weeks to see improvement Usually given as pills, sometimes IVUsually given as pills, sometimes IV Doses and frequency (every day or every Doses and frequency (every day or every

other day) varyother day) vary Initial high doses can lead to more Initial high doses can lead to more

weaknessweakness

PrednisonePrednisone Inexpensive drugInexpensive drug

Side Effects many:Side Effects many:

-Weight gain, puffiness-Weight gain, puffiness

-Facial hair-Facial hair

-Bone thinning*-Bone thinning*

-Stomach irritation*-Stomach irritation*

-Infections*-Infections*

-Diabetes, high blood pressure, glaucoma-Diabetes, high blood pressure, glaucoma

*=other medications can be given for these*=other medications can be given for these

Steroid-Sparing DrugsSteroid-Sparing Drugs“Long-Term”“Long-Term”

General idea is to use these to allow General idea is to use these to allow reduction and elimination of Prednisonereduction and elimination of Prednisone

Or, sometimes to avoid using it altogetherOr, sometimes to avoid using it altogether Require monitoring of lab testsRequire monitoring of lab tests

Blood counts, liver testsBlood counts, liver tests

Steroid-Sparing DrugsSteroid-Sparing Drugs“Long-Term”“Long-Term”

Imuran (azathioprine)Imuran (azathioprine) Most commonly usedMost commonly used Takes 6-12 months to ‘work’Takes 6-12 months to ‘work’

Cellcept (mycophenolate)Cellcept (mycophenolate) Studies have shown it may not ‘work’Studies have shown it may not ‘work’ Takes months to ‘work’ (> 6)Takes months to ‘work’ (> 6)

Cyclosporin or Tacrolimus (FK506)Cyclosporin or Tacrolimus (FK506) Studies show these ‘work’Studies show these ‘work’

Steroid-Sparing DrugsSteroid-Sparing Drugs“Long-Term”“Long-Term”

Others:Others: Cyclophosphamide (Cytoxan)Cyclophosphamide (Cytoxan)

Given by mouth or IVGiven by mouth or IV Reserved for severe diseaseReserved for severe disease

Rituximab (Rituxan)Rituximab (Rituxan) Given IV weekly for 4 weeksGiven IV weekly for 4 weeks Reserved for severe diseaseReserved for severe disease

Longer-TermLonger-TermThymectomyThymectomy

Done since the 1930’s/1940’sDone since the 1930’s/1940’s Not proven Not proven definitivelydefinitively to help to help Data:Data:

1.5 to 2 times higher chance that a patient will 1.5 to 2 times higher chance that a patient will have remission after thymectomyhave remission after thymectomy

But:But: Studies are not controlled or randomizedStudies are not controlled or randomized Other factors go into how patients do (for Other factors go into how patients do (for

example who gets picked to have surgery)example who gets picked to have surgery)

Longer-TermLonger-TermThymectomyThymectomy

International MGTX study ongoingInternational MGTX study ongoing Patients randomized to getting surgery or notPatients randomized to getting surgery or not

Also controversial what kind of thymectomy to Also controversial what kind of thymectomy to dodo More minimal invasive surgeryMore minimal invasive surgery

Considered in patients with generalized Considered in patients with generalized disease, within the first few (2-3) years and all disease, within the first few (2-3) years and all patients with thymomapatients with thymoma

Doing wellDoing well Some diseaseSome disease CrisesCrises

In relation to common medical conditionsIn relation to common medical conditions In relation to common surgical conditionsIn relation to common surgical conditions

Newly Diagnosed-ClinicNewly Diagnosed-Clinic

MestinonMestinon If not fixing weakness, then…If not fixing weakness, then… PrednisonePrednisone IVIGIVIG Eventual taper of prednisone with or Eventual taper of prednisone with or

without a steroid-sparing drugwithout a steroid-sparing drug Get disease stabilizedGet disease stabilized Consider thymectomyConsider thymectomy

Newly Diagnosed-HospitalNewly Diagnosed-Hospital

Plasma Exchange or IVIGPlasma Exchange or IVIG PrednisonePrednisone +/- Mestinon+/- Mestinon Imaging of chest to look for thymomaImaging of chest to look for thymoma

If none, thymectomy can be considered, but If none, thymectomy can be considered, but once patient is stabilized (may be months)once patient is stabilized (may be months)

If yes, then operate when safe medicallyIf yes, then operate when safe medically

Doing fine, maintenanceDoing fine, maintenance

MestinonMestinon Tapering PrednisoneTapering Prednisone +/- a steroid-sparing drug+/- a steroid-sparing drug

Question becomes when to stop the Question becomes when to stop the steroid-sparing drug if patient is in steroid-sparing drug if patient is in remissionremission

ExacerbationsExacerbations

Treat any medical factor that may Treat any medical factor that may contributecontribute

Start or increase PrednisoneStart or increase Prednisone Use IVIG for a course of 3-5 daysUse IVIG for a course of 3-5 days

Sometimes weekly or monthlySometimes weekly or monthly

Difficult to control diseaseDifficult to control disease

Regular IVIG or plasma exchangeRegular IVIG or plasma exchange A different steroid-sparing drugA different steroid-sparing drug Thymectomy (if not done)Thymectomy (if not done)

Medications that affect MGMedications that affect MG

AntibioticsAntibiotics Cipro, Gentamicin, Levaquin, Erythromycin, Cipro, Gentamicin, Levaquin, Erythromycin,

Azithromycin (aka Z-pak)Azithromycin (aka Z-pak) Bo-ToxBo-Tox Less likely:Less likely:

Blood pressure drugsBlood pressure drugs Statin medicationsStatin medications

Other symptoms in MGOther symptoms in MG

Fatigue, fatigue, fatigueFatigue, fatigue, fatigue Adequate sleepAdequate sleep Treatment of painTreatment of pain Treatment of depressionTreatment of depression Review medicationsReview medications Regular exerciseRegular exercise

Thanks!!Thanks!!

MG is diagnosableMG is diagnosable MG is treatableMG is treatable Treatment is individualized, but effective in Treatment is individualized, but effective in

mostmost We need better treatments and answers to We need better treatments and answers to

treatment questions (like thymectomy)treatment questions (like thymectomy)