Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Immediate and Delayed Impact of Oral Glucocorticoid Therapy On Risk of Serious Infection In Patients with Rheumatoid Arthritis: A Nested Case-Control Analysis Using a Weighted Cumulative Dose Model.
Dixon1, William G., Abrahamowicz2, Michal, Beauchamp2, Marie-Eve, Ray3, David W., Bernatsky4, Sasha, Suissa5, Samy, Sylvestre6, Marie-Pierre
Arthritis Research UK Epidemiology Unit, The University of Manchester, Manchester, United Kingdom
McGill University, Montreal, QC
The University of Manchester, Manchester, United Kingdom
McGill UHC/RVH, Montreal, QC
Royal Victoria Hosp, McGill Un, Montreal
University of Montreal, Montreal, QC
The association between glucocorticoid (GC) therapy and serious infection in patients with rheumatoid arthritis (RA) is uncertain. It is unclear which treatment regimes increase risk, what degree of risk is conferred, or what happens to risk on stopping therapy. Most published work uses crude models of exposure e.g. current use, ever use or cumulative dose. These ignore variations of dose with time and apply improbable weights to past therapy. The aim of this study was to explore the application of a novel weighted cumulative dose (WCD) model to examine the risk of serious infection in patients with RA treated with GC therapy compared to no GC therapy within a nested case-control analysis from a Canadian administrative database, and to compare the results with conventional approaches.
A case-control analysis matched 1,851 serious infection cases to up to five controls, selected from 16,207 elderly RA patients using disease modifying anti-rheumatic therapy between 19852003 in RAMQ, Quebec, Canada. Serious infections were identified as the first occurrence of a primary hospital discharge diagnosis of infection. Oral GC dosage was derived from dispensed pharmacy records. Ten conventional multivariable conditional logistic regression models, each representing GC exposure differently, were compared to a WCD model where GC exposure was represented as the weighted sum of past doses. Weights were estimated to reflect the relative importance of doses taken at different times in the past. Co-morbidity, disease severity and DMARDs were potential confounders and adjusted for in all analyses.
All ten conventional models found a statistically significant association between GC exposure and risk of hospitalization for infection. However, the goodness of fit varied considerably depending on the way GC exposure was represented, the time window over which it was considered, and whether GC dose was taken into account. The WCD model predicted risks better than conventional models (>25 AIC units difference). Current and recent doses had the highest impact on current risk. However, doses taken up to 2.5 years ago were also associated with increased infection risk. Accepting some residual confounding by indication, a current GC user of 5mg prednisolone had a 33%, 53% or 105% increased risk of serious infection when used continuously for the last 3 months, 6 months or 3 years, respectively, compared to a non-user. The risk associated with 5mg prednisolone taken for the last 3 years was equivalent to that associated with 30mg taken for the last month. Discontinuing a two-year course of 10mg prednisolone six months ago halved the risk of infection compared to ongoing use.
GC therapy is associated with infection risk in older patients with RA. Current and recent doses have the greatest impact on infection risk but doses taken up to 2.5 years ago still affect the risk. Knowing how risk depends on past pattern of GC use can guide prescribing to minimize infection risk.
To cite this abstract, please use the following information:
Dixon, William G., Abrahamowicz, Michal, Beauchamp, Marie-Eve, Ray, David W., Bernatsky, Sasha, Suissa, Samy, et al; Immediate and Delayed Impact of Oral Glucocorticoid Therapy On Risk of Serious Infection In Patients with Rheumatoid Arthritis: A Nested Case-Control Analysis Using a Weighted Cumulative Dose Model. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :2463