Medical and Surgical Management of MG

1. Medical and Surgical Management of MG Brian A. Crum, MD Department of Neurology Mayo Clinic Rochester, MN MGFA National Meeting, St. Louis May, 2010

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

3. Variables in Treatment • Ocular vs. Generalized vs. Crisis • Types of antibodies (AchR vs. MuSK) • Thymoma or not • Age and other medical conditions • Men vs Women (esp childbearing) • Access to healthcare • Not: Levels of antibodies in the blood

4. Ocular vs. Generalized • Ocular: Just in the eyes • Generalized: Face, arms, legs, neck • 80+% of MG starts in the eyes • Many will ‘generalize’ in the first months-year • Most that DON’T generalize at a year will remain ocular

5. Ocular vs. Generalized • Treatment is mostly symptomatic • If double vision and droopy eyes are a problem, need treatment • Treatment with steroids may reduce the chance of ‘generalizing’ • Thymectomy generally not recommended for just ocular disease

6. Types of Antibodies • MuSK antibody positive MG • Affects face, neck, shoulders, breathing • Tests (like EMG) may not show as much of the MG changes • AchR antibodies are negative • Mestinon/pyridostigmine less effective, may make weakness worse • Plasma Exchange works • Thymectomy probably not

7. Thymoma or Not • 10-20% of MG patients have a thymoma • Most have no symptoms (other than MG) • Found with imaging like CT • Surgery is done to remove tumor • Usually totally removed • If not, chemo or radiation done w/ oncologist • MG is more difficult to treat

8. Overview--Treatments • Short Term • Symptomatic: Mestinon • Immune-mediating: IVIG, Plasma Exchange • Medium Term • Immune-Mediating: Steroids • Long Term • Immune-Mediating: Several • Longer Term • Thymectomy • Goal: Normalize strength, minimal medications (or none)

9. Mestinon (pyridostigmine) • Short-acting • 30-60 minutes to start working, lasts a few hours • Used ‘as needed’ • Patients can experiment with doses • ½ to 1 to 2 pills at a time • 3-6 times a day • Too much can lead to cramps, twitching, diarrhea, sweating, more weakness • Also a longer-acting form (at night)

10. NeuroMuscular Transmission Acetylcholine Ach Esterase Ach receptor Muscle Contraction

11. Short-Term: IVIG/Plasma Exchange • Usually for severe weakness (ie in the hospital) • One not better than the other (in studies on crisis) • IVIG shown to be effective in improving weakness and reducing need for steroids in outpatients with MG

12. IVIG • 3-5 days in a row • Pooled antibodies from blood donors • Screened for transmissible disease • Thought to reduce the immune attack on muscle • Improvement w/in days • Requires and IV in the arm • Expensive, but typically covered • Done more in outpatient setting now

13. Plasma Exchange • “Filtering” of blood through a machine • Typically done every other day for 5-7 exchanges (10-14 days) • May required a larger IV line (central line) placed in neck or chest • Risks of infection or blood clotting • Improvement in days • Usually reserved for hospital patients

14. Medium-Term • Prednisone (the ‘love/hate’ drug) • Proven to work in MG • Takes days to weeks to see improvement • Usually given as pills, sometimes IV • Doses and frequency (every day or every other day) vary • Initial high doses can lead to more weakness

15. Prednisone • Inexpensive drug Side Effects many: -Weight gain, puffiness -Facial hair -Bone thinning* -Stomach irritation* -Infections* -Diabetes, high blood pressure, glaucoma *=other medications can be given for these

16. Steroid-Sparing Drugs“Long-Term” • General idea is to use these to allow reduction and elimination of Prednisone • Or, sometimes to avoid using it altogether • Require monitoring of lab tests • Blood counts, liver tests

17. Steroid-Sparing Drugs“Long-Term” • Imuran (azathioprine) • Most commonly used • Takes 6-12 months to ‘work’ • Cellcept (mycophenolate) • Studies have shown it may not ‘work’ • Takes months to ‘work’ (> 6) • Cyclosporin or Tacrolimus (FK506) • Studies show these ‘work’

18. Steroid-Sparing Drugs“Long-Term” • Others: • Cyclophosphamide (Cytoxan) • Given by mouth or IV • Reserved for severe disease • Rituximab (Rituxan) • Given IV weekly for 4 weeks • Reserved for severe disease

19. Longer-TermThymectomy • Done since the 1930’s/1940’s • Not proven definitively to help • Data: • 1.5 to 2 times higher chance that a patient will have remission after thymectomy • But: • Studies are not controlled or randomized • Other factors go into how patients do (for example who gets picked to have surgery)

20. Longer-TermThymectomy • International MGTX study ongoing • Patients randomized to getting surgery or not • Also controversial what kind of thymectomy to do • More minimal invasive surgery • Considered in patients with generalized disease, within the first few (2-3) years and all patients with thymoma

21. Doing well • Some disease • Crises • In relation to common medical conditions • In relation to common surgical conditions

22. Newly Diagnosed-Clinic • Mestinon • If not fixing weakness, then… • Prednisone • IVIG • Eventual taper of prednisone with or without a steroid-sparing drug • Get disease stabilized • Consider thymectomy

23. Newly Diagnosed-Hospital • Plasma Exchange or IVIG • Prednisone • +/- Mestinon • Imaging of chest to look for thymoma • If none, thymectomy can be considered, but once patient is stabilized (may be months) • If yes, then operate when safe medically

24. Doing fine, maintenance • Mestinon • Tapering Prednisone • +/- a steroid-sparing drug • Question becomes when to stop the steroid-sparing drug if patient is in remission

25. Exacerbations • Treat any medical factor that may contribute • Start or increase Prednisone • Use IVIG for a course of 3-5 days • Sometimes weekly or monthly

26. Difficult to control disease • Regular IVIG or plasma exchange • A different steroid-sparing drug • Thymectomy (if not done)

27. Medications that affect MG • Antibiotics • Cipro, Gentamicin, Levaquin, Erythromycin, Azithromycin (aka Z-pak) • Bo-Tox • Less likely: • Blood pressure drugs • Statin medications

28. Other symptoms in MG • Fatigue, fatigue, fatigue • Adequate sleep • Treatment of pain • Treatment of depression • Review medications • Regular exercise

29. Thanks!! • MG is diagnosable • MG is treatable • Treatment is individualized, but effective in most • We need better treatments and answers to treatment questions (like thymectomy)