Sara Monti1, Kaitlin A Quinn2, Robin Christensen3, David Jayne4, Carol Langford5, Georgia E Lanier6, Alfred Mahr7, Christian Pagnoux8, Maria Bjork Viðarsdóttir9, Peter A Merkel10, Gunnar Tomasson11. 1. Department of Rheumatology, IRCCS Policlinico S. Matteo Foundation, University of Pavia, Pavia, Italy; University of Pavia, PhD in Experimental Medicine, Pavia, Italy. Electronic address: sara.saramonti@gmail.com. 2. Division of Rheumatology, MedStar Georgetown University Hospital, Washington, DC, USA; Systemic Autoimmunity Branch, National Institutes of Health, NIAMS, Bethesda, MD, USA. 3. Musculoskeletal Statistics Unit, The Parker Institute, Bispebjerg and Frederiksberg Hospital & Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Denmark. 4. Department of Medicine, University of Cambridge, United Kingdom. 5. Department of Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland OH, USA. 6. Sherborn, MA, USA. 7. Clinic for Rheumatology, Cantonal Hospital St. Gallen, Switzerland. 8. Department of Medicine, University of Toronto, Toronto, Canada. 9. Reykjavik, Iceland. 10. Division of Rheumatology, Department of Medicine, and Division of Clinical Epidemiology, Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA, USA. 11. Faculty of Medicine, University of Iceland, Reykjavik, Iceland, Department of rheumatology, University Hospital, Iceland. Centre for Rheumatology Research, University Hospital, Iceland.
Abstract
BACKGROUND: A comprehensive review of outcome measures used in randomized controlled trials (RCTs) of ANCA-associated vasculitis (AAV) could advance trial conductance for this disease. METHODS: A systematic literature review of outcome measures (as specified in methods section as primary and/or secondary outcomes) in RCTs of AAV was conducted. Medline, Cochrane CENTRAL, and ClinicalTrials.gov were searched from inception until April 30, 2019 for RCTs enrolling patients with granulomatosis with polyangiitis and/or microscopic polyangiitis. Outcome measures were organized according to domains (e.g. disease activity) and instruments [e.g. Birmingham Vasculitis Activity Score (BVAS)]. RESULTS: Out of 1101 identified records, 68 RCTs were eligible. Disease activity was an outcome domain collected in 67 (98%) of the RCTs. The BVAS was the most widely used instrument for disease assessment but definitions for remissions and relapse varied for the purpose of primary endpoint definitions. Damage, most often assessed by the Vasculitis Damage Index, was an outcome in 30 (44%) of the RCTs. Mortality was specified as an outcome in 26 (38%) studies. The following outcome domains were assessed: patient-reported outcomes (PROs) in 28 (41%), drug exposure/safety in 58 (85%), and biomarkers [acute phase reactants, ANCA levels] in 24 (35%). Timing for outcome assessment differed substantially, with 3, 6, or 12 months being the most frequent time points. CONCLUSION: Outcome measures used in trials in AAV commonly included vasculitis-specific tools for disease assessment, but with heterogeneity in endpoint-definitions and timing of assessments. Other core outcomes in AAV, including PROs, and damage measures, are often omitted in AAV trials.
BACKGROUND: A comprehensive review of outcome measures used in randomized controlled trials (RCTs) of ANCA-associated vasculitis (AAV) could advance trial conductance for this disease. METHODS: A systematic literature review of outcome measures (as specified in methods section as primary and/or secondary outcomes) in RCTs of AAV was conducted. Medline, Cochrane CENTRAL, and ClinicalTrials.gov were searched from inception until April 30, 2019 for RCTs enrolling patients with granulomatosis with polyangiitis and/or microscopic polyangiitis. Outcome measures were organized according to domains (e.g. disease activity) and instruments [e.g. Birmingham Vasculitis Activity Score (BVAS)]. RESULTS: Out of 1101 identified records, 68 RCTs were eligible. Disease activity was an outcome domain collected in 67 (98%) of the RCTs. The BVAS was the most widely used instrument for disease assessment but definitions for remissions and relapse varied for the purpose of primary endpoint definitions. Damage, most often assessed by the Vasculitis Damage Index, was an outcome in 30 (44%) of the RCTs. Mortality was specified as an outcome in 26 (38%) studies. The following outcome domains were assessed: patient-reported outcomes (PROs) in 28 (41%), drug exposure/safety in 58 (85%), and biomarkers [acute phase reactants, ANCA levels] in 24 (35%). Timing for outcome assessment differed substantially, with 3, 6, or 12 months being the most frequent time points. CONCLUSION: Outcome measures used in trials in AAV commonly included vasculitis-specific tools for disease assessment, but with heterogeneity in endpoint-definitions and timing of assessments. Other core outcomes in AAV, including PROs, and damage measures, are often omitted in AAV trials.
Authors: Kaitlin A Quinn; Sara Monti; Robin Christensen; David Jayne; Carol A Langford; Georgia E Lanier; Alfred Mahr; Christian Pagnoux; Beverley Shea; Maria Bjork Viðarsdóttir; Gunnar Tomasson; Peter A Merkel Journal: Semin Arthritis Rheum Date: 2022-04-28 Impact factor: 5.431
Authors: Allyson C Egan; Andreas Kronbichler; Irmgard Neumann; Alessandra Bettiol; Nicholas Carlson; Maria C Cid; Giacomo Emmi; Seerapani Gopaluni; Lorraine Harper; Thomas Hauser; Mark A Little; Raashid A Luqmani; Alfred Mahr; Mark McClure; Aladdin J Mohammad; Karl Emil Nelveg-Kristensen; Sophie Ohlsson; Chen Au Peh; Matthew Rutherford; Beatriz Sanchez Alamo; Jennifer Scott; Mårten Segelmark; Rona M Smith; Wladimir M Szpirt; Gunnar Tomasson; Giorgio Trivioli; Augusto Vaglio; Michael Walsh; Maria Wester Trejo; Kerstin Westman; Ingeborg M Bajema; David R W Jayne Journal: Kidney Int Rep Date: 2022-05-25