Subcutaneous Immunoglobulin in Myasthenia Gravis: Results of a North American Open Label Study (N4.002)

Objective: Objectives: To evaluate the efficacy, safety and tolerability of subcutaneous immunoglobulin (SCIg) in the treatment in myasthenia gravis (MG) patients who are on IVIg as part of routine clinicalcare. Background: Background: IVIg has been demonstrated to improve the Quantitative MG (QMG) score as compared to placebo and in another study to be efficacious in comparison to plasma exchange. In routine care, SCIg might be easier to administer than IVIg. Design/Methods: Methods: This multi-center North American open label prospective investigator-initiated study had 2 components: IVIg Screening Phase (ISP; Weeks −10 to −1) followed by Experimental Treatment Phase (ETP; Weeks 0 to 12). We hypothesized that more than 65% of the patients entering the ETP would have stable QMG score (primary outcome) at Week 12. We recruited 23 patients in the ISP and 22 entered the ETP. 12/22(54.5%) were females and 18(78%) were white, with mean age 51.4 years±17. We had complete ETP QMG data on 19/22; one subject withdrew from ISP owing to worsened condition and two subjects withdrew before Week 4 (needle dislike). The per protocol primary statistical analysis was conducted for n=22 subjects using a one-sided z-test of proportions at the 5% significance level. Sensitivity analyses were conducted using a cohort of n=22 subjects using ‘worst-case’ imputation scenario as well as post hoc analysis. Results: Findings: On primary analysis, 19/22 (86.4%; 95% CI: 0.72–1.00)were treatment “successes” (p=0.018). Sensitivity analysis using the ‘worst-case’ imputation resulted in 17/22 (77.3%;0.60–0.95) declared as treatment success (p=0.114). Post hoc analysis of the primary outcome confirmed treatment success in 17/20 (85%;0.69–1.00) (p=0.0304). There was no difference in the secondary outcome measures though MG composite was better at Week 12. SCIg was safe and well tolerated in this population. Conclusions: Conclusion: Most MG patients who were doing well on IVIg maintained disease stability for another 12 weeks once transitioned to SCIg. Disclosure: Dr. Dimachkie has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alnylam, Audentes, Biomarin, Catalyst, CSL-Behring, Genzyme, Mallinckrodt, Momenta, Novartis, NuFactor, Octapharma, RMS Medical, Sanofi, Shire and Terumo. Dr. Dimachkie has received research support from Alexion, Alnylam, Amicus, Biomarin, Bristol-Myers Squibb, Catalyst, CSL-Behring, FDA/OPD, GlaxoSmithKline, Genentech, Grifols, MDA, NIH, Novartis, Genzyme, Octapharma, UCB Biopharma, Viromed and TMA. Dr. Bril has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with CSL Behring, UCB, Alnylam, Alexion, Grifols, Octapharma, Shire, Pfizer and Bionevia. Dr. Bril has received research support from CSL Behring, UCB, Alnylam, Alexion, Grifols, Octapharma, Shire, and Bionevia. Dr. Levine has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Griffons, Alexion, Nufactor, Diplomat, Shire, and Corinthian Reference Labs. Dr. Levine holds stock and/or stock options in Corinthian Reference Labs. Dr. Levine has received research support from Alnylam Pharmaceuticals and Malinckrodt. Dr. Trivedi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sanofi. Dr. Trivedi has received research support from Sanofi, CSL Behring. Dr. Silvestri has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion Pharmaceuticals and OptionCare. Dr. Phadnis has nothing to disclose. Dr. Saperstein has nothing to disclose. Dr. Nations has received research support from Catalyst Pharmaceutical. Dr. Katzberg has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with CSL Behring, Amazentis, Flexpharma, Momenta, Octapharma, Terumo, Grifols, and Sanofi Genzyme. Dr. Katzberg has received research support from CSL Behring, Octapharma and Grifols. Dr. Wolfe has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Grifols, Shire, and Alexion. Dr. Wolfe has received research support from ArgenX, Ra, and Immunovant. Dr. Herbelin has nothing to disclose. Dr. Higgs has nothing to disclose. Dr. Heim has nothing to disclose. Dr. McVey has nothing to disclose. Dr. Rico has nothing to disclose. Dr. Statland has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Acceleron Pharma, Inc., Expansion Therapeutics, , Fulcrum Therapeutics, Genea Biocells, and Strongbridge Biopharma. Dr. Statland has received research support from FSH Society, Muscular Dystrophy Association, and the National Institutes of Health. Dr. Barohn has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with NuFACTOR Specialty Pharmacy. Dr. Barohn has received research support from Alexion, BioMarin, Cytokinetics, Eli Lilly, Ionis, Neuraltus, Novartis, PTC Therapeutics, Sanofi/Genzyme, Sarepta, Teva. Dr. Barohn has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with NuFACTOR Specialty Pharmacy. Dr. Barohn has received research support from Alexion, BioMarin, Cytokinetics, Eli Lilly, Ionis, Neuraltus, Novartis, PTC Therapeutics, Sanofi/Genzyme, Sarepta, Teva. Dr. Pasnoor has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with TerumoBCT, Alexion Pharmaceuticals and Momenta Pharmaceuticals.