POS0079 THE EFFECT OF ORAL GLUCOCORTICOID TREATMENT DURATION ON THE RISK OF SERIOUS INFECTIONS FOR PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: K. S. Duch, B. G. Soussi, S. Kristensen, S. Lundbye-Christensen, M. Bøgsted, R. G. Skals, L. Dreyer
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Glucocorticoid (GC) is widely used in the treatment of rheumatoid arthritis (RA), but studies have found a dose-dependent risk of serious infections (SI). The large randomised controlled trial GLORIA found a reduction in disease activity but a 24% increased risk of adverse events for RA patients with low dose add on GC therapy [1]. Another study found that cumulative GC dose in the previous 6 months may increase the current infection risk [2]. However, the information about the effect of treatment duration on the risk of SI in the literature is scarce. Using a method combining cloning and weighting, we can compare different treatment durations using observational data without introducing immortal time bias [3]. <h3>Objectives:</h3> We aim to investigate the effect of oral GC treatment duration on the cumulative risk of SI for patients with RA. <h3>Methods:</h3> We used Danish national registers and the nationwide clinical quality register DANBIO to include 19 463 patients with an RA diagnosis and a first visit in DANBIO between 2006 and 2018. Patients were followed from first registered visit until death, SI, migration, or 31 December 2018, whichever came first. SI was defined as an infection requiring hospitalization. Treatment duration was defined as continuous prescription redemptions every 60 days or less since first visit in DANBIO. Information on covariates such as age, sex, and disease activity score 28 (DAS28) were included. We compared the effect of treatment duration &lt;90 days and 90 to 360 days, with nonexposed on the cumulative risk of SI using the cloning and weighting method (3). The method consisting of three steps (i) cloning patients to all treatment strategies, (ii) censoring clones when they failed to adhere with the assigned strategy, (iii) weighting to correct for bias introduced by cloning. The first 30 days since first visit the patients were included in all exposure groups to allow for late treatment initiation. A generalised linear model was used to calculate the relative risk (RR) for SI for each 30 days since first visit. The analysis was adjusted for time since first visit, age, diabetes mellitus, sex, and time varying DAS28 and bDMARD use. Time varying covariates were updated at start of each 30 days interval. Patients without DAS28 at first visit were excluded. Censoring weights were calculated using a pooled logistic regression and stabilised based on non-time varying variables. Bootstrap 95% confidence intervals (95%CI) from 1000 samples were calculated. <h3>Results:</h3> Patient population is presented in Table 1. In total, 1861 SI were observed before cloning. After cloning, 1705 SI were observed for nonexposed, 199 for &lt;90 days, and 150 for 90 to 360 days. Figure 1 illustrates the RR for a GC exposed women, without diabetic, non bDMARD exposed, with an age of 60 and a DAS28 score between 2 and 4 compared to a similar nonexposed patient. The RR for both exposed groups (&lt;90 and 90 to 360 days) was stabile until about 1 year from first visit after which both curves drop rapidly before flattening at about 2 years. The maximum RR for &lt;90 days is observed at 8 months since first visit (RR: 4.7 (95%CI: 4.1 to 5.2)) and at 7 months after first visit for 90 to 360 days (RR: 6.5 (95%CI: 5.4 to 7.3)). <h3>Conclusion:</h3> GC treatment duration for &lt;90 and 90 to 360 days is associated with a higher risk of cumulative SI compared to nonexposed, especially the first year but also up to two years since first visit in RA patients. <h3>REFERENCES:</h3> [1] Boers M, et al. Low dose, add-on prednisolone in patients with rheumatoid arthritis aged 65+: The pragmatic randomised, double-blind placebo-controlled GLORIA trial. Ann Rheum Dis. 2022;81(7):925–36. [2] Dixon WG, et al. Immediate and delayed impact of oral glucocorticoid therapy on risk of serious infection in older patients with rheumatoid arthritis: a nested case – control analysis. Ann Rheum Dis. 2012 Jul;71(7):1128–33. [3] Hernán MA. How to estimate the effect of treatment duration on survival outcomes using observational data. BMJ. 2018;10–3. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Kirsten S. Duch: None declared, Bolette Gylden Soussi Novo Nordisk stocks, Salome Kristensen: None declared, Søren Lundbye-Christensen: None declared, Martin Bøgsted: None declared, Regitze G. Skals: None declared, Lene Dreyer has received research grant (paid to her institution) from BMS and Abbvie outside the current manuscript. She is member of the steering committee of the Danish Rheumatology Quality Registry (DANBIO, DRQ), which receives public funding from the hospital owners and funding from pharmaceutical companies.