Jianhua Wu1, Adam Keeley1, Christian Mallen1, Ann W Morgan1, Mar Pujades-Rodriguez2. 1. School of Dentistry (Wu), University of Leeds; Leeds Institute for Data Analytics (Keeley, Morgan, Pujades-Rodriguez), University of Leeds, Leeds, UK; Arthritis Research UK Primary Care Centre (Mallen), University of Keele, Staffordshire, UK; Leeds Institute of Cardiovascular and Metabolic Medicine (Morgan), School of Medicine, University of Leeds; NIHR Leeds Biomedical Research Centre (Morgan), Leeds Teaching Hospitals NHS Trust; Leeds Institute of Health Sciences (Pujades-Rodriguez), School of Medicine, University of Leeds, Leeds, UK. 2. School of Dentistry (Wu), University of Leeds; Leeds Institute for Data Analytics (Keeley, Morgan, Pujades-Rodriguez), University of Leeds, Leeds, UK; Arthritis Research UK Primary Care Centre (Mallen), University of Keele, Staffordshire, UK; Leeds Institute of Cardiovascular and Metabolic Medicine (Morgan), School of Medicine, University of Leeds; NIHR Leeds Biomedical Research Centre (Morgan), Leeds Teaching Hospitals NHS Trust; Leeds Institute of Health Sciences (Pujades-Rodriguez), School of Medicine, University of Leeds, Leeds, UK M.D.M.PujadesRodriguez@leeds.ac.uk.
Abstract
BACKGROUND: Most patients with polymyalgia rheumatica or giant cell arteritis are treated with glucocorticoid therapy in primary care. We estimated dose-response risks of infection for this population in England. METHODS: We conducted a retrospective record-linkage study involving a cohort of people with polymyalgia rheumatica or giant cell arteritis registered in family practices across England (1998-2017). Estimates of first occurring infection per level of time-variant current and cumulative dose were obtained using Kaplan-Meier methods and multilevel proportional-hazards Cox models. RESULTS: Of 39 938 patients attending 389 family practices, 22 234 (55.7%) had at least 1 infection over a median follow-up period of 4.8 years, with 5937 (26.7%) requiring hospital admission and 1616 (7.3%) dying within 7 days of diagnosis. Cumulative risks of all-cause infection were 18.3% (95% confidence interval [CI] 17.9%-18.7%) at 1 year, 54.7% (95% CI 54.1%-55.2%) at 5 years and 76.9% (95% CI 76.2%-77.5%) at 10 years. Lower respiratory tract infections, conjunctivitis and herpes zoster were the most commonly diagnosed infections. The increases in adjusted hazard ratios (HRs) for all-cause infection per 5 mg prednisolone-equivalent daily dose increase and per 1000 mg cumulative dose increase in the last year from the patient's end date of follow-up were 1.13 (95% CI 1.12-1.14) and 1.50 (95% CI 1.49-1.52), respectively. Adjusted HRs associated with periods of current glucocorticoid versus no glucocorticoid use ranged from 1.48 (95% CI 1.39-1.57) for fungal to 1.70 (95% CI 1.60-1.80) for bacterial infection. Stepwise dose-related associations were found for bacterial, viral, parasitic and fungal infections, irrespective of patient age, duration of underlying chronic disease and baseline vaccination status. INTERPRETATION: We quantified the excess risk of all-cause, bacterial, viral, parasitic and fungal infection conferred by oral glucocorticoids in people with polymyalgia rheumatica or giant cell arteritis and found strong dose responses for all types, even at daily doses of less than 5 mg prednisolone.
BACKGROUND: Most patients with polymyalgia rheumatica or giant cell arteritis are treated with glucocorticoid therapy in primary care. We estimated dose-response risks of infection for this population in England. METHODS: We conducted a retrospective record-linkage study involving a cohort of people with polymyalgia rheumatica or giant cell arteritis registered in family practices across England (1998-2017). Estimates of first occurring infection per level of time-variant current and cumulative dose were obtained using Kaplan-Meier methods and multilevel proportional-hazards Cox models. RESULTS: Of 39 938 patients attending 389 family practices, 22 234 (55.7%) had at least 1 infection over a median follow-up period of 4.8 years, with 5937 (26.7%) requiring hospital admission and 1616 (7.3%) dying within 7 days of diagnosis. Cumulative risks of all-cause infection were 18.3% (95% confidence interval [CI] 17.9%-18.7%) at 1 year, 54.7% (95% CI 54.1%-55.2%) at 5 years and 76.9% (95% CI 76.2%-77.5%) at 10 years. Lower respiratory tract infections, conjunctivitis and herpes zoster were the most commonly diagnosed infections. The increases in adjusted hazard ratios (HRs) for all-cause infection per 5 mg prednisolone-equivalent daily dose increase and per 1000 mg cumulative dose increase in the last year from the patient's end date of follow-up were 1.13 (95% CI 1.12-1.14) and 1.50 (95% CI 1.49-1.52), respectively. Adjusted HRs associated with periods of current glucocorticoid versus no glucocorticoid use ranged from 1.48 (95% CI 1.39-1.57) for fungal to 1.70 (95% CI 1.60-1.80) for bacterial infection. Stepwise dose-related associations were found for bacterial, viral, parasitic and fungal infections, irrespective of patient age, duration of underlying chronic disease and baseline vaccination status. INTERPRETATION: We quantified the excess risk of all-cause, bacterial, viral, parasitic and fungal infection conferred by oral glucocorticoids in people with polymyalgia rheumatica or giant cell arteritis and found strong dose responses for all types, even at daily doses of less than 5 mg prednisolone.
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