Response Rates in Placebo arm of MG Clinical Trials (P5.4-025)

Objective: To analyze the extent of improvement in reported outcomes measures in patients in the placebo groups in Myasthenia Gravis (MG) clinical trials Background: Various immunosuppressive agents used in MG clinical practice have failed to meet primary end points in randomized double blind placebo controlled clinical trials. Patients in the placebo group of MG clinical trials are treated with prednisone and other standard of care therapies. Clinical improvement from these therapies within the placebo group could have led to the failure of research trials to meet primary end points. Many MG outcomes measures are used in multiple randomized clinical trials allowing for comparison of clinical improvement across studies. Design/Methods: We reviewed published manuscripts of all randomized double blind clinical trials in myasthenia gravis that used the quantitative MG (QMG) and MG-Activities of daily living (MG-ADL) scales. We analyzed the improvements in clinical outcome measures and evaluated clinical trial phase, mode of drug/placebo administration and duration of the clinical trails. We also reviewed the inclusion criteria and whether MG patients were refractory at the time of enrollment. Results: We analyzed 8 recent MG clinical trails evaluating 5 different therapies. Clinical trial duration ranged from 3 to 12 months. Three trials required refractory MG status before recruitment. QMG was used as a primary or secondary end point in 8 trials and MG-ADL was used as a primary or secondary end point in 7 clinical trials. In the placebo groups, the mean QMG score improvement was 2.24 (−0.3–3.67) and mean MG-ADL score improvement was 2.03 (0.6–2.8). Conclusions: Average improvement in QMG and MG-ADL scores in the placebo arm of MG trials meets criteria for clinically significant change. Future clinical trials in MG should consider this observation and ascertain goals for primary and secondary end points for clinical trials accordingly. Disclosure: Dr. Muppidi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion Pharmaceuticals. Dr. Samara has nothing to disclose. Dr. Lin has nothing to disclose. Dr. Goyal has nothing to disclose.