Alvise Berti1, Divi Cornec2, Jose R Medina Inojosa3, Eric L Matteson4, M Hassan Murad5. 1. Immunology, Rheumatology, Allergy and Rare Diseases Department, San Raffaele Scientific Institute, Milan, and Santa Chiara Hospital, Trento, Italy; Division of Pulmonary and Critical Care Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN. 2. Division of Pulmonary and Critical Care Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN; INSERM UMR1227, Lymphocytes B et Autoimmunité, Université de Bretagne Occidentale, CHU de Brest, Brest, France. 3. Division of Preventive Cardiology, Department of Cardiovascular Medicine, Mayo Clinic 200 First St S.W., Rochester, MN 55905. 4. Division of Rheumatology, Mayo Clinic College of Medicine and Science, Rochester, MN; (f)Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science, Rochester, MN. Electronic address: matteson.eric@mayo.edu. 5. Evidence-based Practice Center, Mayo Clinic College of Medicine and Science, Rochester, MN.
Abstract
BACKGROUND: To better communicate the results of randomized controlled trials (RCTs) of giant cell arteritis (GCA), we propose the use of the fragility index (FI), which is an intuitive measure defined as the minimum number of subjects whose status would have to change (e.g., from having the outcome to not) to render a statistically significant result nonsignificant, or vice-versa. METHODS: We conducted a systematic review and random-effects meta-analysis of RCTs of glucocorticoid (GC) sparing strategies for relapse-free maintenance in GCA, and used the FI to simplify the presentation of results. RESULTS: Ten RCTs (nine phase II and one phase III enrolling 645 subjects) were included. Tocilizumab, IV GC and methotrexate significantly improved the likelihood of being relapse free with relative risks and 95% confidence intervals of 3.54 (2.28, 5.51), 5.11 (1.39, 18.81) and 1.54 (1.02, 2.30); respectively. The median FI was 4.5 (range, 1-28), and was generally higher for negative RCTs (n = 6; median FI 4.5) than for positive RCTs (n = 4; median FI 3.5). The range of FI per treatment was (1-8) for methotrexate, (2-6) for anti-TNF agents, 4 for abatacept, 3 for IV GC pulses and (4-28) for tocilizumab. CONCLUSION: Tocilizumab, IV GC and methotrexate improve the likelihood of being relapse-free in subjects with GCA. Assessment of GC sparing strategies in GCA has long depended on imprecise trials that would change significance if outcomes were reversed for a handful of subjects. FI may be used in rheumatology to simplify communication of statistical significance and overcome limitations of p-value.
BACKGROUND: To better communicate the results of randomized controlled trials (RCTs) of giant cell arteritis (GCA), we propose the use of the fragility index (FI), which is an intuitive measure defined as the minimum number of subjects whose status would have to change (e.g., from having the outcome to not) to render a statistically significant result nonsignificant, or vice-versa. METHODS: We conducted a systematic review and random-effects meta-analysis of RCTs of glucocorticoid (GC) sparing strategies for relapse-free maintenance in GCA, and used the FI to simplify the presentation of results. RESULTS: Ten RCTs (nine phase II and one phase III enrolling 645 subjects) were included. Tocilizumab, IV GC and methotrexate significantly improved the likelihood of being relapse free with relative risks and 95% confidence intervals of 3.54 (2.28, 5.51), 5.11 (1.39, 18.81) and 1.54 (1.02, 2.30); respectively. The median FI was 4.5 (range, 1-28), and was generally higher for negative RCTs (n = 6; median FI 4.5) than for positive RCTs (n = 4; median FI 3.5). The range of FI per treatment was (1-8) for methotrexate, (2-6) for anti-TNF agents, 4 for abatacept, 3 for IV GC pulses and (4-28) for tocilizumab. CONCLUSION:Tocilizumab, IV GC and methotrexate improve the likelihood of being relapse-free in subjects with GCA. Assessment of GC sparing strategies in GCA has long depended on imprecise trials that would change significance if outcomes were reversed for a handful of subjects. FI may be used in rheumatology to simplify communication of statistical significance and overcome limitations of p-value.
Authors: Thomas Daikeler; Peter M Villiger; Christophe Schmitt; Laura Brockwell; Mylène Giraudon; Mauro Zucchetto; Lisa Christ; Bettina Bannert Journal: Arthritis Res Ther Date: 2022-06-04 Impact factor: 5.606
Authors: Muhammad Shahzeb Khan; Rohan Kumar Ochani; Asim Shaikh; Muhammad Shariq Usman; Naser Yamani; Safi U Khan; M Hassan Murad; John Mandrola; Rami Doukky; Richard A Krasuski Journal: Circ Cardiovasc Qual Outcomes Date: 2019-12-11