. 2023 Sep 5;101(10):442-451.

doi: 10.1212/WNL.0000000000207278. Epub 2023 Apr 19.

Addressing Outcome Measure Variability in Myasthenia Gravis Clinical Trials

Collaborators, Affiliations

Collaborators

for MGNet Clinical Trial Outcome Measure Working Group:
Inmaculada Aban, Robin Conwit, Helen Girma, Amanda Guidon, Alison Hall, Eileen King, Linda Kusner, Nancy Law, Samantha Masterson, Thomas Morel, Glen Nuckolls, Kevin O'Connor, Betty Soliven, Tina Urv, Joan Wincentsen

Affiliations

¹ From the Duke University School of Medicine (J.T.G.), Durham, NC; argenx US (J.T.G.), Boston, MA; University of Miami School of Medicine (M.B., V.G.), FL; Biohaven Pharmaceuticals (V.G.), New Haven, CT; University of California, Irvine (A.A.H.); The University of North Carolina School of Medicine (J.F.H.), Chapel Hill; Division of Neurology (C.B.-T.), Department of Medicine, University of Toronto, Ontario, Canada; Yale University School of Medicine (R.J.N.), New Haven, CT; Columbia University (I.L.), New York, NY; Medical University of South Carolina (K.R.), Charleston; Kansas University Medical Center (M.M.D.), Kansas City; School of Public Health (G.R.C.), University of Alabama at Birmingham; and George Washington University School of Medicine & Health Sciences (H.J.K.), DC. jeffrey.guptill@duke.edu mbenatar@med.miami.edu.
² From the Duke University School of Medicine (J.T.G.), Durham, NC; argenx US (J.T.G.), Boston, MA; University of Miami School of Medicine (M.B., V.G.), FL; Biohaven Pharmaceuticals (V.G.), New Haven, CT; University of California, Irvine (A.A.H.); The University of North Carolina School of Medicine (J.F.H.), Chapel Hill; Division of Neurology (C.B.-T.), Department of Medicine, University of Toronto, Ontario, Canada; Yale University School of Medicine (R.J.N.), New Haven, CT; Columbia University (I.L.), New York, NY; Medical University of South Carolina (K.R.), Charleston; Kansas University Medical Center (M.M.D.), Kansas City; School of Public Health (G.R.C.), University of Alabama at Birmingham; and George Washington University School of Medicine & Health Sciences (H.J.K.), DC.

PMID: 37076302
PMCID: PMC10491448
DOI: 10.1212/WNL.0000000000207278

Addressing Outcome Measure Variability in Myasthenia Gravis Clinical Trials

Jeffrey T Guptill et al. Neurology. 2023.

. 2023 Sep 5;101(10):442-451.

doi: 10.1212/WNL.0000000000207278. Epub 2023 Apr 19.

Collaborators

for MGNet Clinical Trial Outcome Measure Working Group:
Inmaculada Aban, Robin Conwit, Helen Girma, Amanda Guidon, Alison Hall, Eileen King, Linda Kusner, Nancy Law, Samantha Masterson, Thomas Morel, Glen Nuckolls, Kevin O'Connor, Betty Soliven, Tina Urv, Joan Wincentsen

Affiliations

¹ From the Duke University School of Medicine (J.T.G.), Durham, NC; argenx US (J.T.G.), Boston, MA; University of Miami School of Medicine (M.B., V.G.), FL; Biohaven Pharmaceuticals (V.G.), New Haven, CT; University of California, Irvine (A.A.H.); The University of North Carolina School of Medicine (J.F.H.), Chapel Hill; Division of Neurology (C.B.-T.), Department of Medicine, University of Toronto, Ontario, Canada; Yale University School of Medicine (R.J.N.), New Haven, CT; Columbia University (I.L.), New York, NY; Medical University of South Carolina (K.R.), Charleston; Kansas University Medical Center (M.M.D.), Kansas City; School of Public Health (G.R.C.), University of Alabama at Birmingham; and George Washington University School of Medicine & Health Sciences (H.J.K.), DC. jeffrey.guptill@duke.edu mbenatar@med.miami.edu.
² From the Duke University School of Medicine (J.T.G.), Durham, NC; argenx US (J.T.G.), Boston, MA; University of Miami School of Medicine (M.B., V.G.), FL; Biohaven Pharmaceuticals (V.G.), New Haven, CT; University of California, Irvine (A.A.H.); The University of North Carolina School of Medicine (J.F.H.), Chapel Hill; Division of Neurology (C.B.-T.), Department of Medicine, University of Toronto, Ontario, Canada; Yale University School of Medicine (R.J.N.), New Haven, CT; Columbia University (I.L.), New York, NY; Medical University of South Carolina (K.R.), Charleston; Kansas University Medical Center (M.M.D.), Kansas City; School of Public Health (G.R.C.), University of Alabama at Birmingham; and George Washington University School of Medicine & Health Sciences (H.J.K.), DC.

PMID: 37076302
PMCID: PMC10491448
DOI: 10.1212/WNL.0000000000207278

Abstract

An increasing number of clinical trials are enrolling patients with myasthenia gravis (MG). A lack of standardization in the performance of outcome measures leads to confusion among site research teams and is a source of variability in clinical trial data. MGNet, the NIH-supported Rare Disease Clinical Research Network for MG, views standardization of MG outcome measures as a critical need. To address this issue, a group of experts summarized key outcome measures used in MG clinical trials and a symposium was convened to address issues contributing to outcome measure variability. Consensus recommendations resulted in changes to outcome measure instructions and, in some cases, modifications to specific instruments. Recommended changes were posted for public commentary before finalization. Changes to the MG-Activities of Daily Living, MG-Quality of Life-15r, and MG-Impairment Index were limited to adding details to the administration instructions. Recommendations for proper positioning of participants and how to score items that could not be performed because of non-MG reasons were provided for the MG Composite. The Quantitative MG (QMG) score required the most attention, and changes were made both to the instructions and the performance of certain items resulting in the QMG-Revised. The Postintervention Status was believed to have a limited role in clinical trials, except for the concept of minimal manifestation status. As a next step, training materials and revised source documents, which will be freely available to study teams, will be created and posted on the MGNet website. Further studies are needed to validate changes made to the QMG-Revised.

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Conflict of interest statement

J.T. Guptill has consulted for Immunovant, Alexion, Apellis, Momenta, Ra Pharma, Becton Dickinson, Cabaletta Bio, Regeneron, argenx, Sanofi, Janssen, UCB, Toleranzia, and Piedmont Pharmaceuticals. He received industry grant support from UCB pharma for a fellowship training grant. He has served as a site investigator for Alexion, Janssen, UCB Pharma, Argenx, and Takeda. He received grant/research support from NIH (NIAID, National Institute of Neurological Disorders and Stroke, NIMH), Myasthenia Gravis Foundation of America, and Centers for Disease Control and Prevention. He is currently an employee of argenx. M. Benatar has consulted for Alexion, Immunovant, Takeda, UCB, Ad Scientam, and Sanofi. He receives research funding from Alexion and Immunovant. He has served as the site principal investigator for MG trials sponsored by Alexion, UCB, and the NIH. V. Granit received honoraria as a consultant or advisory board member from Alexion Pharmaceuticals, Argenx, Immunovant Inc., and Amylyx Pharmaceuticals Inc. He is employed by Biohaven Pharmaceuticals. A.A. Habib reports no relevant disclosures. J.F. Howard reports research support (paid to his institution) from Alexion Pharmaceuticals, Argenx, Cartesian Therapeutics, the Centers for Disease Control and Prevention (Atlanta, GA), the Myasthenia Gravis Foundation of America, the Muscular Dystrophy Association, the NIH (including the National Institute of Neurological Disorders and Stroke and the National Institute of Arthritis and Musculoskeletal and Skin Diseases), PCORI, Ra Pharmaceuticals (now UCB Biosciences), and Millennium Pharmaceuticals/Takeda Pharmaceuticals; honoraria from Alexion Pharmaceuticals, Argenx, F. Hoffman-LaRoche Ltd., Immunovant Inc., Ra Pharmaceuticals (now UCB Biosciences), Regeneron Pharmaceuticals, and Sanofi US and nonfinancial support from Alexion Pharmaceuticals, Argenx, Ra Pharmaceuticals (now UCB Biosciences), and Toleranzia AB. C. Barnett-Tapia has received honoraria as consultant or member of advisory board from Alexion, Sanofi, and Argenx. She is the primary developer of the MGII and may receive royalties for its use. R.J. Nowak reports no relevant disclosures. I. Lee reports no relevant disclosures. K. Ruzhansky has served on advisory boards for Alexion, Argenx, Immunovant, and UCB/Ra, has served as a site PI for Alexion, Argenx, UCB, and Janssen, and has grant funding from MGFA. M.M. Dimachkie serves or recently served as a consultant for Abcuro, Amazentis, ArgenX, Astellas, Catalyst, Cello, Covance/Labcorp, CSL-Behring, EcoR1, Janssen, Kezar, MDA, Medlink, Momenta, NuFactor, Octapharma, Priovant, Ra Pharma/UCB, Roivant Sciences Inc, Sanofi Genzyme, Shire Takeda, Scholar Rock, Spark Therapeutics, Abata/Third Rock, UCB Biopharma, and UpToDate. He received research grants or contracts or educational grants from Alexion, Alnylam Pharmaceuticals, Amicus, Biomarin, Bristol-Myers Squibb, Catalyst, Corbus, CSL-Behring, FDA/OOPD, GlaxoSmithKline, Genentech, Grifols, Kezar, Mitsubishi Tanabe Pharma, MDA, NIH, Novartis, Octapharma, Orphazyme, Ra Pharma/UCB, Sanofi Genzyme, Sarepta Therapeutics, Shire Takeda, Spark Therapeutics, The Myositis Association, UCB Biopharma/RaPharma, Viromed/Healixmith, & TMA. G.R. Cutter reports no relevant disclosures. H.J. Kaminski is a consultant for Roche, Cabaletta Bio, and UCB Pharmaceuticals and is a CEO and CMO of ARC Biotechnology, LLC, based on US Patent 8,961,98. He is the principal investigator of the Rare Disease Network for Myasthenia Gravis (MGNet) National Institute of Neurological Disorders and Stroke, U54 NS115054, Targeted Therapy for Myasthenia Gravis. R41 NS110331 to ARC Biotechnology, and coinvestigator for R43NS124329 MV2C2 antibody as a new therapeutic for myasthenia gravis to Mimivax, LLC. Go to Neurology.org/N for full disclosures.

Figures

**Figure. Overview of Methods for Standardizing MG Outcome Measures**
¹Refer to eAppendix 1 (links.lww.com/WNL/C754) for list of attendees. ²Groups notified of public commentary: AANEM Connect, AAN Synapse, Alexion, Argenx, Biosensics, Cabaletta Bio, Clinical and Translational Science Award sites, Conquer MG, Horizon Therapeutics, Janssen, MGNet clinical sites, Muscular Dystrophy Association, Muscle Study Group, Myasthenia Gravis Foundation of America (posted on website), Rare Disease Clinical Research Networks (including NIH staff), Rick's Real Neuromuscular Friends, Signant, and UCB Pharma. ³Next steps of process, currently pending. AAN = American Academy of Neurology; AANEM = American Association of Neuromuscular & Electrodiagnostic Medicine; MG = myasthenia gravis.

See this image and copyright information in PMC

References

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Addressing Outcome Measure Variability in Myasthenia Gravis Clinical Trials

Collaborators

Affiliations

Addressing Outcome Measure Variability in Myasthenia Gravis Clinical Trials

Authors

Collaborators

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Abstract

Conflict of interest statement

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References

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