Michael K Hehir1, Lisa D Hobson-Webb2, Michael Benatar2, Carolina Barnett2, Nicholas J Silvestri2, James F Howard2, Diantha Howard2, Amy Visser2, Brian A Crum2, Richard Nowak2, Rachel Beekman2, Aditya Kumar2, Katherine Ruzhansky2, I-Hweii Amy Chen2, Michael T Pulley2, Shannon M LaBoy2, Melissa A Fellman2, Shane M Greene2, Mamatha Pasnoor2, Ted M Burns2. 1. From the Larner College of Medicine at the University of Vermont (M.K.H., D.H., S.M.G.), Burlington; Duke University School of Medicine (L.D.H.-W.), Durham, NC; University of Miami Health System (M.B., M.A.F.), FL; University of Toronto School of Medicine (C.B.), Canada; SUNY Buffalo Jacobs School of Medicine (N.J.S.), NY; UNC School of Medicine (J.F.H.), Chapel Hill, NC; Mayo Clinic (A.V., B.A.C.), Rochester, MN; Yale School of Medicine (R.N., R.B., A.K.), New Haven, CT; Medical University of South Carolina (K.R., I.-H.A.C.), Columbia; University of Florida (M.T.P., S.M.L., Gainesville; University of Kansas Medical Center (M.P.), Kansas City; and University of Virginia School of Medicine (T.M.B.), Charlottesville. Michael.hehir@uvmhealth.org. 2. From the Larner College of Medicine at the University of Vermont (M.K.H., D.H., S.M.G.), Burlington; Duke University School of Medicine (L.D.H.-W.), Durham, NC; University of Miami Health System (M.B., M.A.F.), FL; University of Toronto School of Medicine (C.B.), Canada; SUNY Buffalo Jacobs School of Medicine (N.J.S.), NY; UNC School of Medicine (J.F.H.), Chapel Hill, NC; Mayo Clinic (A.V., B.A.C.), Rochester, MN; Yale School of Medicine (R.N., R.B., A.K.), New Haven, CT; Medical University of South Carolina (K.R., I.-H.A.C.), Columbia; University of Florida (M.T.P., S.M.L., Gainesville; University of Kansas Medical Center (M.P.), Kansas City; and University of Virginia School of Medicine (T.M.B.), Charlottesville.
Abstract
OBJECTIVE: To evaluate the efficacy of rituximab in treatment of anti-muscle-specific kinase (MuSK) myasthenia gravis (MG). METHODS: This was a multicenter, blinded, prospective review, comparing anti-MuSK-positive patients with MG treated with rituximab to those not treated with rituximab. The primary clinical endpoint was the Myasthenia Gravis Status and Treatment Intensity (MGSTI), a novel outcome that combines the Myasthenia Gravis Foundation of America (MGFA) postintervention status (PIS) and the number and dosages of other immunosuppressant therapies used. A priori, an MGSTI of level ≤2 was used to define a favorable outcome. Secondary outcomes included modified MGFA PIS of minimal manifestations or better, mean/median prednisone dose, and mean/median doses of other immunosuppressant drugs. RESULTS: Seventy-seven of 119 patients with anti-MuSK MG evaluated between January 1, 2005, and January 1, 2015, at 10 neuromuscular centers were selected for analysis after review of limited clinical data by a blinded expert panel. An additional 22 patients were excluded due to insufficient follow-up. Baseline characteristics were similar between the rituximab-treated patients (n = 24) and the controls (n = 31). Median follow-up duration was >3.5 years. At last visit, 58% (14/24) of rituximab-treated patients reached the primary outcome compared to 16% (5/31) of controls (p = 0.002). Number needed to treat for the primary outcome is 2.4. At last visit, 29% of rituximab-treated patients were taking prednisone (mean dose 4.5 mg/day) compared to 74% of controls (mean dose 13 mg/day) (p = 0.001 and p = 0.005). CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with anti-MuSK MG, rituximab increased the probability of a favorable outcome.
OBJECTIVE: To evaluate the efficacy of rituximab in treatment of anti-muscle-specific kinase (MuSK) myasthenia gravis (MG). METHODS: This was a multicenter, blinded, prospective review, comparing anti-MuSK-positive patients with MG treated with rituximab to those not treated with rituximab. The primary clinical endpoint was the Myasthenia Gravis Status and Treatment Intensity (MGSTI), a novel outcome that combines the Myasthenia Gravis Foundation of America (MGFA) postintervention status (PIS) and the number and dosages of other immunosuppressant therapies used. A priori, an MGSTI of level ≤2 was used to define a favorable outcome. Secondary outcomes included modified MGFA PIS of minimal manifestations or better, mean/median prednisone dose, and mean/median doses of other immunosuppressant drugs. RESULTS: Seventy-seven of 119 patients with anti-MuSKMG evaluated between January 1, 2005, and January 1, 2015, at 10 neuromuscular centers were selected for analysis after review of limited clinical data by a blinded expert panel. An additional 22 patients were excluded due to insufficient follow-up. Baseline characteristics were similar between the rituximab-treated patients (n = 24) and the controls (n = 31). Median follow-up duration was >3.5 years. At last visit, 58% (14/24) of rituximab-treated patients reached the primary outcome compared to 16% (5/31) of controls (p = 0.002). Number needed to treat for the primary outcome is 2.4. At last visit, 29% of rituximab-treated patients were taking prednisone (mean dose 4.5 mg/day) compared to 74% of controls (mean dose 13 mg/day) (p = 0.001 and p = 0.005). CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with anti-MuSKMG, rituximab increased the probability of a favorable outcome.
Authors: Susanna Brauner; Ann Eriksson-Dufva; Max Albert Hietala; Thomas Frisell; Rayomand Press; Fredrik Piehl Journal: JAMA Neurol Date: 2020-08-01 Impact factor: 18.302
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Authors: Fredrik Piehl; Ann Eriksson-Dufva; Anna Budzianowska; Amalia Feresiadou; William Hansson; Max Albert Hietala; Irene Håkansson; Rune Johansson; Daniel Jons; Ivan Kmezic; Christopher Lindberg; Jonas Lindh; Fredrik Lundin; Ingela Nygren; Anna Rostedt Punga; Rayomand Press; Kristin Samuelsson; Peter Sundström; Oskar Wickberg; Susanna Brauner; Thomas Frisell Journal: JAMA Neurol Date: 2022-09-19 Impact factor: 29.907
Authors: Raffi Topakian; Fritz Zimprich; Stephan Iglseder; Norbert Embacher; Michael Guger; Karl Stieglbauer; Dieter Langenscheidt; Jakob Rath; Stefan Quasthoff; Philipp Simschitz; Julia Wanschitz; David Windisch; Petra Müller; Dierk Oel; Günther Schustereder; Stefan Einsiedler; Christian Eggers; Wolfgang Löscher Journal: J Neurol Date: 2019-01-16 Impact factor: 4.849