Serious infection risk in rheumatoid arthritis compared with non-inflammatory rheumatic and musculoskeletal diseases: a US national cohort study

Abstract

Objectives: To identify serious infection (SI) risk by aetiology and site in patients with rheumatoid arthritis (RA) compared with those with non-inflammatory rheumatic and musculoskeletal diseases (NIRMD).

Methods: Patients participating in FORWARD from 2001 to 2016 were assessed for SIs; defined by infections requiring hospitalisation, intravenous antibiotics or followed by death. SIs were categorised by aetiology and site. SI risk was assessed through Cox proportional hazards models. Best models were selected using machine learning Least Absolute Shrinkage and Selection Operator (LASSO) methodology.

Results: Among 20 361 patients with RA and 6176 patients with NIRMD, 1600 and 276 first SIs were identified, respectively. Incidence of SIs was higher in RA compared with NIRMD (IRR = 1.5; 95% CI 1.2 to 1.5). The risk persisted after adjusting using the LASSO model (HR 1.7; 95% CI 1.5 to 1.8), but attenuated when additionally adjusted for glucocorticoid use (HR 1.3; 95% CI 1.2 to 1.5). SI risk was significantly higher in RA versus NIRMD for bacterial infections as well as for respiratory, skin, bone, joint, bloodstream infections and sepsis irrespective of glucocorticoid use. Compared with NIRMD, SI risk was significantly increased in patients with RA who were in moderate and high disease activity but was similar to those in low disease activity/remission (p trend < 0.001).

Conclusions: The risk of all SIs, particularly bacterial, respiratory, bloodstream, sepsis, skin, bone and joint infections are significantly increased in patients with RA compared with patients with NIRMD. This infection risk appears to be greatest in those with higher RA disease activity.

Keywords: cohort study; non-inflammatory rheumatic disease; rheumatoid arthritis; serious infection.

Figure 1

Patients with RA in remission/low, moderate and high disease activity according to the PAS (Patient activity Score) scale on the x axis. HRs of all serious infections on y axis (adjusting for age, sex, race, residency (urban vs rural), RA disease duration, diabetes, pulmonary disease, fractures, prior infection, smoking status, Modified Rheumatic Disease Comorbidity Index, education level and vaccination status) per LASSO selection. GC, glucocorticoids; LASSO, least absolute shrinkage and selection operator; NIRMD, non-inflammatory rheumatic and musculoskeletal diseases; RA, rheumatoid arthritis.

Figure 2

Patients with RA on csDMARDs with and without GC, bDMARDs/tofacitinib with and without GC on the x axis. HR of all seriousinfections on y axis (adjusting for age, sex, race, Health Assessment Questionnaire (HAQ), pain scale, Modified Rheumatic Disease Comorbidity Index, education level, RA disease duration, residency (urban vs rural), smoking status, and vaccination status). bDMARDs, biological disease-modifying antirheumatic drugs; csDMARD, conventional synthetic disease-modifying antirheumatic drugs; GC, glucocorticoids; NIRMD, non-inflammatory rheumatic and musculoskeletal diseases, RA, rheumatoid arthritis.