Thymectomy for Myasthenia Gravis? YES! www.rrnmf.com 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

Thymectomy Rx for MG Perlo, et al 1971 Thymectomy – 267 pts Complete remission – 34% Improvement – 41% Non-thymectomy – 417 pts Complete remission – 17% Improvement – 11% Time to remission in thymectomy pts 25% 1st yr 40% 2nd yr 55% 3rd yr

A Treatment Carol: Thymectomy Revisited Michael P. McQuillen, M.D. and Mary G. Leone, M.D. Neurology 1977; 12:1103 – 1106.

Thymectomy Practice Parameter Gronseth and Barohn, Neurology 2000 27 Class II studies non-random, non-prospective Surg vs. no-surg 1953-1998 RESULTS: THY pts more likely to do better RR med free rem 2.1 higher for THY RR asymp 1.6 higher for THY RR imp 1.7 higher for THY PROB: confounding variables: THYM pts younger, female, more severe non-random and non-std outcomes REC – RC trial

Randomized Blinded Trial of Thymectomy for MG Newsom-Davis, Wolfe, Cutter, Kaminski, Jaretski Randomized/controlled NIH trial REQ – gen, AChR Ab+ All pts go on prednisone All get transternal thymectomy Blinded evaluations OUTCOME: Pred dose and QMG at 3 yrs QUESTION: Do THY pts do better than pred alone? Difficult/slow enrollment but enrollment complete (# 126 patients) Most subjects outside USA Wolfe G, et al. NEJM 2016;375:511-522

Wolfe et al. Thymectomy in MG (New England Journal of Medicine 2016;375:511-522) OMG Score (Mean±SE) by Treatment Group QMG difference: 2.85 pts (99.5% CI 0.47-5.22; p<0.001) Time-Weighted Average AD Prednisone Dose (Mean±SE) by Treatment Group Prednisone dose difference: 44 mg vs 60 mg (95% CI 7-25 mg; p<0.001)

Secondary Analyses: Wolfe et al. NEJM 2016;375:511-522   Treatment Group Mean±SD or no./N (%) Estimated Difference (95% CI) P Value Prednisone Alone Thymectomy +prednisone Time-weighted average prescribed AD prednisone dose (mg)a 59.3 ± 28.4 (N=56) 43.4 ± 23.1 (N=62) 16.0 (6.6-25.4) 0.001 Penalized time-weighted average AD prednisone dose (mg; max dose)a,b 72.9 ± 37.4 46.7 ± 24.9 (N=61) 26.3 (14.7-37.8) < 0.001 Penalized time-weighted AD average prednisone dose (mg; dose at start)a,c 68.1 ± 38.3 45.6 ± 24.3 22.5 (10.6-34.4) Time-weighted average MG Activities of Daily Livinga,d 3.41 ± 2.58 (N=55) 2.24 ± 2.09 1.17 (0.31-2.03) 0.008 MG ADL at month 12 3.33 ± 3.40 (N=54) 1.92 ± 2.73 (N=61) 1.42 (0.28-2.55) 0.01 MG ADL at month 24 3.11 ± 2.93 (N=53) 2.02 ± 2.78 (N=59) 1.10 (0.03-2.17) 0.04 MG ADL at month 36 2.69 ± 2.80 (N=51) 2.14 ± 2.92 (N=59) 0.55 (-0.53-1.63) 0.32 Azathioprine usee 28/58 (48) 11/65 (17) 31.4% (15.6%,47.1%) Plasma exchange usee 9/58 (16) 10/65 (15) 0.1% (-12.7%,12.9%) ~1 Intravenous immunoglobulin usee 23/58 (40) 22.7% (7%,38.3%) 0.005 Minimal Manifestation Statuse at month 12f 20/54 (37) 41/61 (67) 30.2% (12.7%-47.6%) at month 24f 20/53 (38) 39/59 (66) 28.4% (10.6%-46.2%) 0.003 at month 36f 24/51 (47) 39/58 (67) 20.2% (1.9%-38.5%) 0.03 Hospitalization for MG exacerbation Months 0-24: # of patientsg 17/60 (28) 6/66 (9) 19.2% (5.9%, 32.6%) 0.006 Cumulative daysh 26.4 ± 28.9 5.5 ± 2.9 0.004 Months 0-36: # of patientsg 22/60 (37) 27.6% (13.6%, 41.6%) <0.001 22.5± 27.1 8.7 ± 7.7 0.21 Method 1 = maximum dose Method 2 = Last dose prior to initiation of Prednison

Thymectomy for MG Now a Controlled Trials Exists! Positive study! SUMMARY Now a Controlled Trials Exists! Positive study! But Response May Not be Immediate Measured in Months to Years No Guarantee of Improvement Numerous Procedures Thymoma is an absolute indication Not rec for: Ocular Very young children Greater than 60, or, ? > 70, or ? > 80 (Depends on how old the Rx Neurologist is) TYPE YEAR Sternal Splitting Early 1900’s Maximally Invasive 1980’s Transcervical 1988 Video-Assisted Thoracoscopic Surgery Late 90’s Robotics (DaVinci) Early 2000’s