Clinical outcome measures
Initial subject stratification was based on three clinical outcome measures, which had been collected prospectively at 0 (baseline) and six months (M6, N = 92) over the course of the MGTX trial. The 6 month time point was used as a treatment response in the clinical trial was beginning to be seen and that a biomarker would be of greatest clinical value. Although subjects were treated with either thymectomy plus prednisone or prednisone alone, the groups were combined for the purpose of identification of common treatment responsive biomarkers. All analysis was performed in Excel and R environment. The MGTX study used designation of minimal manifestation status (MMS), the quantitative MG score (QMG), and the MG-activities of daily living (MG-ADL) to assess treatment response. We applied each of these measures to define treatment response as 1) MMS status obtained at 6 months, 2) QMG improvement of >40 percent from baseline vs. no response or worsening, and 3) MG-ADL >40% improvement vs. no improvement or worsening. Subjects with low to moderate improvement in QMG or ADL scores (1–40%) were not included in our analyses. We made these dichotomous definitions of extremely high and low responders with the expectation of a greater likelihood of discovery treatment-predictive markers. These treatment responses were then correlated with lipidomic and metabolomics results from baseline.Only moderate correlation exists among outcome measures indicating that they measure different characteristics of MG severity [