身 RRNME EARN FAST RICK S RI Randomized controlled trials of ww.rrnmfcom Methotrexate mycophenolate in MG Richard」. Baron,MD Gary Gronseth, MD Chair, Department of Neurology Vice Chair, Department of Neurology Gertrude and dewey Ziegler Professor of University of Kansas Medical Center Neurology Kansas city, ks University distinguished Professor Vice Chancellor for research University of Kansas Medical Center Kansas city, Ks
Randomized Controlled Trials of Methotrexate & Mycophenolate in MG Richard J. Barohn, MD 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 Gary Gronseth, MD Vice Chair, Department of Neurology University of Kansas Medical Center Kansas City, KS www.rrnmf.com
Mycophenolate Mofetil (CellCept) Mechanism: select/rev cytostatic eff on t&B cells Early Studies · Ciafaloni2001 8/12(67%)improved in 2 mos Chaudhry 2001 50%of 20 Mg pts improved in 6-12 mos ·CoS2000 59%of 29 MG pts improved in 6-12 mos Meriggioli et al 2003 °85pts-73%imp Meriggioli et al 2003 Blinded RCT-14 pts/5 months Rx MM-QMG imp 2.5 Plac-QMG imp 0.24(p=0.30)
Mechanism: select/rev cytostatic eff on T&B cells Early Studies • Ciafaloni 2001 • 8/12 (67%) improved in 2 mos • Chaudhry 2001 • 50% of 20 MG pts improved in 6-12 mos • Cos 2000 • 59% of 29 MG pts improved in 6-12 mos • Meriggioli et al 2003 • 85 pts-73% imp • Meriggioli et al 2003 • Blinded RCT-14 pts/5 months Rx • MM-QMG imp 2.5 • Plac-QMG imp 0.24 (p=0.30) Mycophenolate Mofetil (CellCept)
Mycophenolate Mofetil Rand/ Control Trials in Mg Sanders colleagues (MSG Aspreva sponsored-138 Neurology 2008; 71: 394 subjects(Sanders et al Neurol Investigator initiated funded 2008;71400) by FDA-ODG Can already be on prednisone Must be achr-Ab pos ·9 month tria No prior Is Rx 2.5 gm MM Vs plac All placed on pred 20 10-QMG3 mos .20-MMT. MG-ADL AChR-Ab, SFEMG °80 subjects
Mycophenolate Mofetil Rand/Control Trials in MG • Sanders & colleagues (MSG Neurology 2008;71:394) • Investigator initiated funded by FDA-ODG • Must be AChR-Ab pos • No prior IS Rx • 2.5 gm MM vs. plac • All placed on pred 20 • 1 o – QMG 3 mos • 2 o – MMT, MG-ADL • AChR-Ab, SFEMG • 80 subjects • Aspreva sponsored-138 subjects (Sanders et al Neurol 2008;71:400) • Can already be on prednisone • 9 month trial
Mycophenolate Mofetil Rand/Control Trials in MG Sanders colleagues(MSG Neurology quantitative 2008;71394) myasthenia gravis score over ti y treatment group Week Vertical bars indicate one SEM Aspreva sponsored-138 subjects(Sanders Figure 2 ntotal Quantitative Myasthenia Gravis score(QMO S)in the et al Neuro/ 2008; 71: 400) RESULTS FOR BOTH NO SIGNIFICANT DIFFERENCE The and point includes the weak 36 and early termination viait Early termination nalysen aton carnied forward method tor the week 30vs
Mycophenolate Mofetil Rand/Control Trials in MG Sanders & colleagues (MSG Neurology 2008;71:394) Aspreva sponsored-138 subjects (Sanders et al Neurol 2008;71:400) RESULTS FOR BOTH: NO SIGNIFICANT DIFFERENCE!
Mycophenolate Mofetil Rand/ Control Trials Why Negative? Drug does not work Prednisone improved all pts and masked MM effect Studies were not long enough Endpoints were not good enough Non-homogenous populations enrolled
Mycophenolate Mofetil Rand/Control Trials Why Negative? •Drug does not work • Prednisone improved all pts and masked MM effect • Studies were not long enough • Endpoints were not good enough •Non-homogenous populations enrolled