Serious Infection Risk Increased for RA vs Noninflammatory Rheumatic and Musculoskeletal Diseases

Tapering DMARD Therapy in Rheumatoid Arthritis
Tapering DMARD Therapy in Rheumatoid Arthritis
The study examined serious infection risk in patients with rheumatoid arthritis compared with patients with non-inflammatory rheumatic and musculoskeletal diseases.

Serious infection (SI) risk is elevated in patients with rheumatoid arthritis (RA) compared with patients with noninflammatory rheumatic and musculoskeletal diseases (NIRMD), according to research results published in RMD Open. In addition, RA disease activity was found to be correlated with patients’ level of risk.

Researchers conducted a longitudinal cohort study to identify the risk for serious infection in patients with RA vs in patients with NIRMD. Data from 2001 to 2016 were prospectively collected from FORWARD, The National Databank for Rheumatic Diseases.

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In total, 20,361 patients with RA and 6176 patients with NIRMD were included in the cohort, resulting in 81,499 and 20,665 patient-years of observation and 1600 and 276 first SIs, respectively. Patients in the RA group vs those in the NIRMD group were younger (66.8±12.0 years vs 72±11.6 years), were more likely to have ever smoked (50.6% vs 40.6%) and to have a lower body mass index (28.4±7.5 kg/m2 vs 30.6±8.5 kg/m2).

Overall, compared with the NIRMD group, the RA group had higher incidence rate ratios (IRRs) of all SIs, opportunistic SIs, and herpes zoster SIs (IRRs, 1.5, 3.0, and 2.2, respectively). The most frequently identified first SIs by etiology were bacterial, and by site were respiratory (49.3% and 56.8% in the RA group vs 43.8% and 57.2% in the NIRMD group, respectively). Incidence rates for both herpes zoster and opportunistic SIs were “2 to 3 times higher in RA compared with NIRMD,” according to researchers of the study. Fungal SIs were also more frequent in RA compared with NIRMD.

Data were adjusted for age and sex, which resulted in the risk for all SIs increasing in the RA group compared with the NIRMD group (hazard ratio [HR], 1.8; 95% CI, 1.5-2.0). The risk was attenuated when the models accounted for glucocorticoid use; however, the risk remained statistically significant. Following multivariable adjustment, the RA group, compared with the NIRMD group, had a significantly higher risk for respiratory, abdominal, bloodstream, sepsis, skin, bone, and joint SIs.

When categorized by disease activity, patients with RA in remission or with low disease activity had a lower incidence rate than patients with moderate or high disease activity (IR, 13.4 vs 26.7 vs 41.3, respectively). A notable uptrend in SI risk was observed in multivariable assessments of RA disease activity and SI risk (P =<.001). For treatment modality, patients with RA who were treated only with conventional synthetic disease-modifying antirheumatic drugs had increased SI compared with patients treated with biologic disease-modifying antirheumatic drugs or tofacitinib (HR, 1.3 and 1.1, respectively). SI risk in both groups increased when patients were also treated with glucocorticoids (HR, 2.7 and 2.8, respectively).

Study limitations included race and sex of patients of whom a majority were white and women, which suggests that the results may not be generalizable, and the fact that there could have been participation and recall bias due to the patient-reported, longitudinal nature of the study.

“Clinicians should weigh the potential SI risk associated with aggressive treatment strategies in patients with RA while targeting and sustaining remission or low disease activity,” the researchers concluded.


Mehta B, Pedro S, Ozen G, et al. Serious infection risk in rheumatoid arthritis compared with non-inflammatory rheumatic and musculoskeletal diseases: a US national cohort study. RMD Open. 2019;5:e000935.