Jessica Widdifield1,2, Michal Abrahamowicz3,4, J Michael Paterson3,4, Anjie Huang3,4, J Carter Thorne3,4, Janet E Pope3,4, Bindee Kuriya3,4, Marie-Eve Beauchamp3,4, Sasha Bernatsky3,4. 1. From the Sunnybrook Research Institute, Holland Bone and Joint Research Program, Toronto, Ontario; McGill University, Department of Epidemiology, Biostatistics and Occupational Health; Research Institute of the McGill University Health Centre, Department of Clinical Epidemiology, and Centre for Outcomes Research and Evaluation, Montreal, Quebec; ICES; University of Toronto, Institute of Health Policy, Management and Evaluation, Toronto; McMaster University, Department of Family Medicine, Hamilton; Southlake Regional Health Centre, Department of Medicine, Newmarket; Western University, Department of Epidemiology and Biostatistics; St. Joseph's Health Care, Department of Medicine, London; Mount Sinai Hospital, Department of Medicine, Toronto, Ontario, Canada. jessica.widdifield@utoronto.ca. 2. J. Widdifield, PhD, Sunnybrook Research Institute, Holland Bone and Joint Research Program, and McGill University, Department of Epidemiology, Biostatistics and Occupational Health, and Research Institute of the McGill University Health Centre, Department of Clinical Epidemiology, ICES, and University of Toronto, Institute of Health Policy, Management and Evaluation; M. Abrahamowicz, PhD, McGill University, Department of Epidemiology, Biostatistics and Occupational Health, and Research Institute of the McGill University Health Centre, Centre for Outcomes Research and Evaluation; J.M. Paterson, MSc, ICES, and University of Toronto, Institute of Health Policy, Management and Evaluation, and McMaster University, Department of Family Medicine; A. Huang, MSc, ICES; J.C. Thorne, MD, FRCPC, Southlake Regional Health Centre, Department of Medicine; J.E. Pope, MD, FRCPC, MPH, Western University, Department of Epidemiology and Biostatistics, and St. Joseph's Health Care, Department of Medicine; B. Kuriya, MD, FRCPC, SM, Mount Sinai Hospital, Department of Medicine; M.E. Beauchamp, PhD, Research Institute of the McGill University Health Centre, Centre for Outcomes Research and Evaluation; S. Bernatsky, MD, FRCPC, PhD, McGill University, Department of Epidemiology, Biostatistics and Occupational Health, and Research Institute of the McGill University Health Centre, Centre for Outcomes Research and Evaluation. jessica.widdifield@utoronto.ca. 3. From the Sunnybrook Research Institute, Holland Bone and Joint Research Program, Toronto, Ontario; McGill University, Department of Epidemiology, Biostatistics and Occupational Health; Research Institute of the McGill University Health Centre, Department of Clinical Epidemiology, and Centre for Outcomes Research and Evaluation, Montreal, Quebec; ICES; University of Toronto, Institute of Health Policy, Management and Evaluation, Toronto; McMaster University, Department of Family Medicine, Hamilton; Southlake Regional Health Centre, Department of Medicine, Newmarket; Western University, Department of Epidemiology and Biostatistics; St. Joseph's Health Care, Department of Medicine, London; Mount Sinai Hospital, Department of Medicine, Toronto, Ontario, Canada. 4. J. Widdifield, PhD, Sunnybrook Research Institute, Holland Bone and Joint Research Program, and McGill University, Department of Epidemiology, Biostatistics and Occupational Health, and Research Institute of the McGill University Health Centre, Department of Clinical Epidemiology, ICES, and University of Toronto, Institute of Health Policy, Management and Evaluation; M. Abrahamowicz, PhD, McGill University, Department of Epidemiology, Biostatistics and Occupational Health, and Research Institute of the McGill University Health Centre, Centre for Outcomes Research and Evaluation; J.M. Paterson, MSc, ICES, and University of Toronto, Institute of Health Policy, Management and Evaluation, and McMaster University, Department of Family Medicine; A. Huang, MSc, ICES; J.C. Thorne, MD, FRCPC, Southlake Regional Health Centre, Department of Medicine; J.E. Pope, MD, FRCPC, MPH, Western University, Department of Epidemiology and Biostatistics, and St. Joseph's Health Care, Department of Medicine; B. Kuriya, MD, FRCPC, SM, Mount Sinai Hospital, Department of Medicine; M.E. Beauchamp, PhD, Research Institute of the McGill University Health Centre, Centre for Outcomes Research and Evaluation; S. Bernatsky, MD, FRCPC, PhD, McGill University, Department of Epidemiology, Biostatistics and Occupational Health, and Research Institute of the McGill University Health Centre, Centre for Outcomes Research and Evaluation.
Abstract
OBJECTIVE: We evaluated the associations between time-varying methotrexate (MTX) use and risk of cardiovascular events (CVE) in patients with rheumatoid arthritis (RA). METHODS: We studied an inception cohort of 23,994 patients with RA diagnosed after their 65th birthday. Multivariable Cox regression models were fit to evaluate the associations between time-varying MTX use, controlling for other risk factors, and time to CVE. Alternative models assessed the cumulative duration of MTX use over the (1) first year, (2) previous year (recent use), and (3) entire duration of followup. We also assessed whether the strength of the association varied over time. RESULTS: Over 115,453 patient-years (PY), 3294 (13.7%) patients experienced a CVE (28.5 events per 1000 PY; 95% CI 27.6-29.5). In the multivariable analyses, the model assessing time-varying continuous use in the most recent year yielded the best fit. Increasing recent MTX use was associated with lower CVE risks (HR 0.79 for continuous use vs no use in past 12 months, 95% CI 0.70-0.88; p < 0.0001). Greater MTX use in the first year after cohort entry was also protective (HR 0.84, 95% CI 0.72-0.96; p = 0.0048), but this effect decreased with increasing followup. In contrast, longer MTX use during the entire followup was not clearly associated with CVE risk (HR 0.98, 95% CI 0.95-1.01; p = 0.1441). CONCLUSION: We observed about a 20% decrease in CVE associated with recent continuous MTX use. Greater MTX use in the first year of cohort entry also appeared to be important in the association between MTX and CVE risk.
OBJECTIVE: We evaluated the associations between time-varying methotrexate (MTX) use and risk of cardiovascular events (CVE) in patients with rheumatoid arthritis (RA). METHODS: We studied an inception cohort of 23,994 patients with RA diagnosed after their 65th birthday. Multivariable Cox regression models were fit to evaluate the associations between time-varying MTX use, controlling for other risk factors, and time to CVE. Alternative models assessed the cumulative duration of MTX use over the (1) first year, (2) previous year (recent use), and (3) entire duration of followup. We also assessed whether the strength of the association varied over time. RESULTS: Over 115,453 patient-years (PY), 3294 (13.7%) patients experienced a CVE (28.5 events per 1000 PY; 95% CI 27.6-29.5). In the multivariable analyses, the model assessing time-varying continuous use in the most recent year yielded the best fit. Increasing recent MTX use was associated with lower CVE risks (HR 0.79 for continuous use vs no use in past 12 months, 95% CI 0.70-0.88; p < 0.0001). Greater MTX use in the first year after cohort entry was also protective (HR 0.84, 95% CI 0.72-0.96; p = 0.0048), but this effect decreased with increasing followup. In contrast, longer MTX use during the entire followup was not clearly associated with CVE risk (HR 0.98, 95% CI 0.95-1.01; p = 0.1441). CONCLUSION: We observed about a 20% decrease in CVE associated with recent continuous MTX use. Greater MTX use in the first year of cohort entry also appeared to be important in the association between MTX and CVE risk.
Authors: Der-Yuan Chen; Tatsuya Sawamura; Richard A F Dixon; José Luis Sánchez-Quesada; Chu-Huang Chen Journal: J Clin Med Date: 2021-05-06 Impact factor: 4.241
Authors: Tate M Johnson; Harlan R Sayles; Joshua F Baker; Michael D George; Punyasha Roul; Cheng Zheng; Brian Sauer; Katherine P Liao; Daniel R Anderson; Ted R Mikuls; Bryant R England Journal: Ann Rheum Dis Date: 2021-05-28 Impact factor: 19.103
Authors: Ana M Fernández-Ortiz; Ana M Ortiz; Silvia Pérez; Esther Toledano; Lydia Abásolo; Miguel A González-Gay; Santos Castañeda; Isidoro González-Álvaro Journal: Arthritis Res Ther Date: 2020-09-11 Impact factor: 5.156