PracticeUpdate

monitoring and clinical metrics from three time points from the COS (baseline and years 1 and 2) are being evaluated in 120 samples per visit to determine whether longitudinal protein data from multiple reaction monitoring can be used to strat- ify participants with dysferlinopathy with respect to future clinical outcome. “The main goals of COS are to better understand the natural progression of dysferlinopathy and to identify the best outcome measures to use in evaluating potential therapies in clinical trials,” noted Dr. Rufibach. “We want to be ready to design and run effective clinical trials once these agents are identified. We are well on our way toward achieving these goals. In addition to the promising protein biomarkers, the clinical analysis is show- ing slow but consistent, significant change over a years' time in numerous functional and strength measures.” www.practiceupdate.com/c /70708 Similarly, limited evidence supports thymectomy in individuals with ocular myasthenia gravis. If the individual is refractory and positive for acetylcholine receptor antibody, however, thymectomy may be considered. MGTX mandated a sternal splitting procedure. www.practiceupdate.com/c/70778 The tumor should be removed in thymo- matous myasthenia gravis. The entire thymus tissue should be removed along with the thymoma. Myasthenic symptoms may or may not improve. Controlled trials involving thoracic sur- gery for a rare disease are difficult, so high-quality evidence about thymectomy remained scarce for decades. Surprisingly, the effects of thymectomy in MGTX were observed as early as 3 to 4 months and were maintained for the entire 3-year study. Individuals with persistent bulbar, respira- tory, or limb weakness should be treated with plasma exchange before surgery. Evidence does not support thymectomy in MuSK, LRP4, or agrin antibody-positive individuals. Individuals with myasthenia gravis with MuSK antibodies were not included but those with MuSK and those who are “double-negative” for antibodies have undergone thymectomy and have done well anecdotally.

provide an effective treatment to those suffering from this debilitating disease," Dr. Rufibach noted. In the pilot phase, participants were split into highly ambulant (n=25) and non-am- bulant (n=25) groups to assess profiles associated with disease progression and to compare profiles with those of healthy age- and sex- matched controls (n=25). Protein biomarkers were combined to improve on the performance of individual proteins. In the technical replication phase, the best-performing protein panels were recalibrated in the same individuals using a targeted platform (multiple reaction monitoring mass spectrometry). In the external replication phase, the mul- tiple reaction monitoring panels with the best performance were analyzed in 145 baseline visit samples from the COS. In the longitudinal phase of the bio- marker study, data from multiple reaction Richard J. Barohn, MD, of the University of Kansas Medical Center in Kansas City, discussed MGTX in a presentation in which he stressed the central role that thymectomy was confirmed to play in the treatment of myasthenia gravis. non-thymomatous myasthenia gravis that had persisted for 75 years since the pro- cedure’s use was first reported by Blalock and colleagues in 1941. Dr. Wolfe concluded that extended trans-sternal thymectomy performed within the first 5 years of disease improves clinical outcomes, reduces immunosup- pressant requirements, and decreases side effect burdens in generalized ace- tylcholine receptor antibody-positive individuals with myasthenia gravis with- out thymoma. This group represents the largest sub-population of individuals with myasthenia gravis.

muscular dystrophy type 2B and Miyoshi myopathy type 1. Due to the rare nature of the disease, molecular signatures that differentiate sufferers from healthy indi- viduals, as well as levels of severity, have not been defined. Dr. Rufibach told Elsevier’s PracticeUpdate , “We have identified clinical outcome measures for future clinical trials in dysferlinopathy. For example, change is being captured in this population con- sistently over 1 year across a range of functional outcomes including the North Star Assessment for Dysferlinopathy, 10 meter walk, Timed Up and Go, and four stair climb and descend.” “Results of both the protein biomarker and COS studies will help us design and run effective clinical trials in dysferlinopathy. We expect to determine how biomarker panels change in patients treated with a potential therapeutic intervention such as gene therapy. The ultimate goal is to immunosuppression with azathioprine (17% vs 48%, P < .001) or were hospitalized for exacerbations (9% versus 37%, P < .001). The number of individuals with treat- ment-associated complications did not differ significantly between groups, but the thymectomy group exhibited fewer treat- ment-associated symptoms (P < .001) and less symptom-related distress (P = .003). The Myasthenia Gravis Activities of Daily Living scale and proportion of individuals reaching minimal manifestation status also favored surgery significantly. Dr. Wolfe explained that the thymec- tomy trial in non-thymomatous generalized myasthenia gravis patients receiving corticosteroids (MGTX) was the first randomized, rater-blinded study of thymectomy in myasthenia gravis. The international trial addressed questions regarding the efficacy of thymectomy in

ICNMD 2018 • PRACTICEUPDATE CONFERENCE SERIES 17