Risk of serious infections in arthritis patients treated with biological drugs: a matched cohort study and development of prediction model

Abstract

Objectives Serious infection is a concern for patients with inflammatory joint diseases treated with biological drugs (bDMARDs). The objectives were to compare risk of serious infection, defined as infection leading to hospitalization, in patients initiating bDMARD treatment with the general population and, second, to develop a simple clinical prediction model and to obtain risk estimates for individual patients. Methods Matched-cohort study based on nationwide registries in Denmark. Patients with rheumatoid arthritis, axial spondyloarthritis and psoriatic arthritis initiating first bDMARD monitored in the DANBIO registry were matched 1:10 by age, gender and postal code with controls from the general population. The risk of serious infection during 12 months’ follow-up was assessed with Cox regression. Prediction models were developed using logistic regression and compared using area under the ROC curve (AUC). Results We included 11 372 patients and 113 715 controls. During follow-up, 522 patients (4.6%) and 1,434 controls (1.3%) developed a serious infection (hazard ratio 3.7, 95% confidence interval: 3.4–4.1). Age-stratified risk was largely similar across diagnoses. A simple prediction model, the “DANBIO infection risk score” based on age and a count of six clinical risk factors had moderate discriminative power (internal validation: AUC 0.69), which was comparable to that of the existing RABBIT risk score (external validation: AUC 0.68). Conclusion Patients with inflammatory joint diseases initiating bDMARD treatment had four times increased risk of serious infection compared with the general population. A simple prediction model, feasible for shared decision-making, was developed to obtain risk estimates for individual patients.

Risk of Severe Infection among Rheumatoid Arthritis Patients on Biological DMARDs: A Population-Based Cohort Study

“…In the last report, the authors reported that the risk of severe infections is moderately increased in users of bDMARDs compared to those receiving csDMARDs. This result is in line with a recent Danish cohort study that demonstrated a hazard ratio for serious infections of 3.7 (95% CI 3.4–4.1) for bDMARDs users compared to non-users [ 22 ]. Studies also suggest that this risk would be higher during the first year after treatment initiation and that patients with a first episode of infection are at a higher risk for subsequent events [ 22 , 23 , 24 ].…”

Serious infections in patients with rheumatoid arthritis and psoriatic arthritis treated with tumour necrosis factor inhibitors: data from register linkage of the NOR-DMARD study

“…The few observational studies assessing IRs of SIs in patients with PsA treated with biologicals have reported widespread estimates from 2.7 to 19.6/100 person-years. [8][9][10][11] The IRs found in our analyses are thus in line with these previously reported estimates.…”

“…The study was not specifically designed to compare the risk of SIs between patient groups, but concluded that the risk is similar. 11 However, in this study, the follow-up period was defined as 12 months regardless of drug discontinuation, and difference in drug retention between patients with RA and PsA were not accounted for. A study using administrative data found no significant difference in risk between patients with RA, PsA and/or severe psoriasis.…”

“…In patients with RA, TNFi therapy is associated with an increased risk of serious infections (SIs) compared with conventional synthetic disease modifying antirheumatic drugs (DMARDs). [4][5][6][7] Few observational studies have addressed incidence rates (IRs) of SIs in PsA [8][9][10][11] and studies comparing the risk of SIs between patients with RA and PsA are sparse. 11 12 The future risk of infections should be considered when making treatment decisions.…”

“… 4–7 Few observational studies have addressed incidence rates (IRs) of SIs in PsA 8–11 and studies comparing the risk of SIs between patients with RA and PsA are sparse. 11 12 The future risk of infections should be considered when making treatment decisions. 13 …”