PracticeUpdate

Thymectomy Continues to Be Successful for MyastheniaGravis

Thymectomy improves clinical outcomes, reduces immunosuppressant requirements, and decreases side effects

R esults of the MGTX trial have provided a defin- itive answer to questions about the efficacy of thymectomy for myasthenia gravis. Fewer individuals who underwent thymectomy needed additional immunosuppression, and they experi- enced fewer adverse events and admissions for myasthenic crises. This outcome from the multi- center, randomized, prospective MGTX trial was reported at ICNMD 2018. Gil I. Wolfe, MD, of the University of Buffalo in New York, and colleagues set out to determine whether the combination of alternate-day prednisone and extended trans-sternal thymectomy after 3 years versus an identical dosing protocol of prednisone alone would: 1. Lead to better outcomes as measured by a time-weighted average of the Quantitative Myasthenia Gravis Score 2. Reduce time-weighted average alternate-day prednisone requirements 3. Reduce the burden of side effects that arise primarily from medications used to treat the disease Participants aged 18 to 65 years and suffering from generalized non-thymomatous acetylcholine receptor antibody-positive myasthenia gravis for

<5 years and Myasthenia Gravis Foundation of America Clinical Classification 2 to 4 were included. Dual primary outcomes were the time-weighted average of the Quantitative Myasthenia Gravis Score and prednisone dose over 3 years. A total of 126 participants with myasthenia gravis were randomized at 36 sites. Individuals who under- went thymectomy showed significant improvement in myasthenia gravis status (time-weighted average Quantitative Myasthenia Gravis Score 6.15 vs 8.99, P < .001) and reduced alternate-day prednisone requirement (32 vs 54 mg, P < .001) after 3 years with benefits observed as early as 9 to 12 months. The ability to withdraw from prednisone completely and remain off it after 3 years also favored surgery (58% vs 20%, P < .01). The ability to withdraw from prednisone correlated with neither duration of disease, age at onset of myasthenia gravis, nor trial enrollment. Histological analysis of thymic follicular hyperplasia, seen in 67% of surgical individuals, failed to corre- late with time-weighted Quantitative Myasthenia Gravis Score or prednisone exposure. Intrathymic fat content, however, correlated directly with time- weighted prednisone exposure (P = .004). In terms of secondary outcomes, fewer indi- viduals who underwent thymectomy required

Dr. Gil I. Wolfe

Protein Biomarkers of Dysferlinopathy Identified

Biomarkers show promise for evaluating and monitoring disease progression and predicting therapeutic effect P rotein biomarkers of dysferlinopa- thy have been identified that hold promise for evaluation and monitor-

replication cohort, area under the curve was 0.89. The best performing panel exhibited an area under the curve of 0.91 with 92% sensitivity and 79% specificity in ambulatory versus non-ambulatory partici- pants. External replication performance of this multiple reaction monitoring panel in COS participants yielded an area under the curve of 0.77. Laura Rufibach, PhD, of the Jain Foundation in Seattle, Washington, explained that dysferlinopathy is a rare neuromuscular disease caused by a deficiency of the dysferlin protein. This deficiency results in progressive skeletal muscle weakness of the limbs, which often leads to an inability to walk. The most common clinical presenta- tions of dysferlinopathy are limb-girdle

ing, as well as for predicting therapeutic outcome, suggests a biomarker discovery program described at ICNMD 2018. Using multiple reaction monitoring, the best performing protein biomarker panel exhibited an area under receiver operat- ing characteristics curve performance of 0.92 with 92% sensitivity and 76% speci- ficity in study participants versus healthy controls. When this panel was tested in the external Clinical Outcome Study for Dysferlinopathy (COS; a multicenter, international, con- sortium study of the natural history of the disease coordinated by Volker Straub, MD, of the University of Newcastle, UK)

Dr. Laura Rufibach

PRACTICEUPDATE CONFERENCE SERIES • ICNMD 2018 16