Severe Infection Risk Increased With RA Onset After bDMARD Introduction

Among patients with RA vs control participants, risk for severe infections was increased after bDMARD introduction.

Risk for severe infection was found to be increased with rheumatoid arthritis (RA) onset after biologic disease-modifying antirheumatic drug (bDMARD) introduction, according to study findings published in Rheumatology.

In a population-based retrospective cohort study, rates of severe infection were compared among patients with RA and non-RA control participants.

Researchers from Arthritis Research Canada collected data for an interrupted time-series study from a database with infection rates in British Columbia. Rates of infection between 1995 and 2001 (before bDMARDs were approved) were compared with rates between 2003 and 2007 (after bDMARDs became available) among patients with RA and control participants.

The RA (N=60,226) and control (N=588,499) groups included individuals with a mean age of 59.1 (SD, 15.9) years and 58.9 (SD, 15.9) years; 66.8% and 66.9% were women; had a Charlson comorbidity index of 0.4 (SD, 1.0) and 0.2 (SD, 0.7); and 23.7% and 1.9% received glucocorticoids, respectively.

In the RA cohort, researchers noted 14,245 severe infection events during a 384,710 person-year (py) follow-up compared with 79,819 severe infection events during a 3,982,833 py follow-up among the control participants. Overall, the average 8-year incidence rate (IR) of severe infections was 37.0 per 1000 py and 20.0 per 1000 py among patients with RA and control participants.

The results suggest that RA onset after bDMARDs introduction is associated with a significant increase in risk of severe infection.

In the RA group, 32,459 were included in the pre-bDMARD analysis and 23,369 in the post-bDMARD analysis; in the control group, the sample sizes were 319,168 and 224,331, respectively.

Stratified by time period, the 8-year IR of severe infections remained elevated in the RA group compared with the control group in the pre-bDMARD (IR, 39.1 vs 21.0 per 1000 py) and post-bDMARD (IR, 34.3 vs 18.7 per 1000 py) cohorts, respectively.

During the 8-year time periods, the rates in severe infections decreased significantly in both the RA (slope, -1.12; P =.0010) and control (slope, -0.63; P <.0001) groups in the pre-bDMARD period and was not significantly changing during the post-bDMARD period among patients with RA (slope, 0.72; P =.0863) but was decreasing significantly among control participants (slope, -0.34; P =.0005).

In the fully adjusted analysis, the 8-year rate of severe infections was higher during the bDMARD period compared with the pre-bDMARD period among patients with RA (adjusted mean difference [aMD], 1.85; 95% CI, 0.81-2.89; P =.0011) but not the control participants (aMD, 0.12; 95% CI, -0.10 to 0.34; P =.2877). The overall difference between the RA and control cohorts was significant (aMD, 1.73; 95% CI, 0.67-2.79; P =.0014).

The trends remained consistent in sensitivity analyses adjusting for aggressive conventional synthetic DMARD use or including total joint arthroplasty-related severe infections.

The study may have been limited by the fact that not all patients in the post-bDMARD period used the bDMARDs.

The study authors concluded, “[W]e found a significant increase in the secular trend in severe infection rates among [patients with] RA diagnosed after the introduction of bDMARDs, but not in general population control [participants]…The results suggest that RA onset after bDMARDs introduction is associated with a significant increase in risk of severe infections.”

This article originally appeared on Rheumatology Advisor


Zhou VY, Lacaille D, Lu N, et al. Risk of severe infections after the introduction of biologic DMARDs in people with newly diagnosed rheumatoid arthritis: a population-based interrupted time-series analysis. Rheumatology. Published online April 4, 2023. doi:10.1093/rheumatology/kead158