Prednisone for MG Richard J. Barohn, MD Gary Gronseth, MD www.rrnmf.com Richard J. Barohn, MD Gary Gronseth, MD Chair, Department of Neurology Vice Chair, Department of Neurology Gertrude and Dewey Ziegler Professor of Neurology University Distinguished Professor Vice Chancellor for Research University of Kansas Medical Center Kansas City, KS

Treatment of MG Cholinesterase Inhibitors Pyridostigmine (Mestinon) Prostigmine (Neostigmine) Immunosuppressive Drug Therapies Plasmapheresis Surgery Thymectomy

Benefit from Alternate-Day Prednisone in Myasthenia Gravis 5 MG Pts Prednisone 100mg every other day Single AM dose With daily K⁺, antacids, low Na/ carb diet All improved in 24-72 hrs 1 CR JR Warmolts, WK Engel. N Engl J Med 1972; 286:17-20

Treatment of Myasthenia Gravis with Prednisone Jenkins RB. Lancet 8 MG pts Rx with prednisone for between 6 and 25 months Alternate day trials 7/8 improved

ALERNATE-DAY PREDNISONE: PRELIMINARY REPORT OF A DOUBLE-BLIND CONTROLLED STUDY Howard et al, Ann NYAS 1976 13 Pts: 6 Pred / 7 Plac 100 mg qod x 6 mo vs. plac All on Anticholinesterase Imp No Imp Rem Pred 3 3 0 Plac 3 4 0 Rep Stim - No Diff Conc: No stats 2° small #s Not all Pred pts imp Some Plac pts imp

Prednisone Rx For MG U. Virginia Experience: Pascuzzi & Johns 116 Pts – Anals Neurol 1984;15:291 Dose – Initiation 60-80 mg/day Maintenance alternate day Early exacerbation 48% 9% required intubation 28% asymptomatic – pharmacologic remission 52% marked improvement 15% moderate improvement 5% no improvement Mean Time t o Max Benefit – 5.5 Months Range 2 weeks to 6 years Only 14% of Responders were able to D/C Prednisone Thymectomy did not improve likelihood of D/C steroids: 8/51 vs. 5/42 Sghirlanzoni et al, Neurol 1984;34:170 60 pts; Imp 72% Evoli et al, Eur Neurol 1992;32:31 104 pts; Imp 81.7%

Treatment of myasthenia gravis with a methylprednisolone pulse: a double blind study Lindberg, Andersen, Lefvert. Acta Neurol Scand 1998;97:370-373 20 pts 10 IVMP / 10 PLAC 2 grams IVMP x 2 days At 2 weeks: IVMP imp muscle fatigue by 27 points PLAC unchanged; P = 0.0006 8/10 responded in IVMP group & 1/9 in PLAC Duration of imp – 4, 6, 6, 8, 10, 14 weeks 1 pt in IVMP reported initial worsening No other AE’s

Prednisone Rx for MG High Dose 100 mg/day x 2 weeks Then 100 mg qod until much better Then taper 5 mg q 2 wks Requires initial inpatient admission Low / Slow Approach Seybold & Drachman 1974 Gradual inc to avoid initial worsening 10 mg/day; inc by 10 mg q 5-7 days Then switch to qod In-between Approach Mycophenolate trial protocol - Pred 20 mg/day No randomized trial of prednisone in MG, but it works! Probably most effective drug for MG Even given potential side effects

MG Treatment Side effects of prednisone Type 2 muscle fiber atrophy But true steroid myopathy rare Hypertension Glucose intolerance (diabetes) Low potassium Fluid retention and weight gain Cataracts Risk of infection Osteoporosis, aseptic femoral necrosis

MG Treatment Concurrent Management Chest X-ray and PPD or new Quantiferon TB blood test prior to treatment Vitamin D and calcium supplementation for prophylaxis against osteoporosis Baseline bone density DEXA scan and then annual Alendronate (Fosamax) as needed Dietary consult to instruct on low carbohydrate, low sodium diet Check potassium, glucose, blood pressure, eyes on follow-up

Corticosteroid Treatment for MG Rx for MG since 1970 Pred can decrease AChR-Ab level (Tindall, 1980) Improvement begins to occur in 2-4 weeks Maximum benefit in 6 months Transient worsening occurs in 50% of patients during first week “Remission” is often steroid dependent Still most effective therapy for MG