Risk of hospitalised infection in rheumatoid arthritis patients receiving biologics following a previous infection while on treatment with anti-TNF therapy

Abstract

Background: The risk of subsequent infections in rheumatoid arthritis (RA) patients who receive biologic therapy after a serious infection is unclear.

Objective: To compare the subsequent risk of hospitalised infections associated with specific biologic agents among RA patients previously hospitalised for infection while receiving anti-tumour necrosis factor (anti-TNF) therapy.

Methods: Using 2006-2010 Medicare data for 100% of beneficiaries with RA enrolled in Medicare, we identified patients hospitalised with an infection while on anti-TNF agents. Follow-up began 61 days after hospital discharge and ended at the earliest of: next infection, loss of Medicare coverage or 18 months after start of follow-up. We calculated the incidence rate of subsequent hospitalised infection for each biologic and used Cox regression to control for potential confounders.

Results: 10 794 eligible hospitalised infections among 10183 unique RA patients who contributed at least 1 day of biologic exposure during follow-up. We identified 7807 person-years of exposure to selected biologics--333 abatacept, 133 rituximab and 7341 anti-TNFs (1797 etanercept, 1405 adalimumab, 4139 infliximab)--and 2666 associated infections. Mean age across biologic exposure cohorts was 64-69 years. The crude incidence rate of subsequent hospitalised infection ranged from 27.1 to 34.6 per 100 person-years. After multivariable adjustment, abatacept (HR: 0.80, 95% CI 0.64 to 0.99) and etanercept (HR: 0.83, 95% CI 0.72 to 0.96) users had significantly lower risks of subsequent infection compared to infliximab users.

Conclusions: Among RA patients who experienced a hospitalised infection while on anti-TNF therapy, abatacept and etanercept were associated with the lowest risk of subsequent infection compared to other biologic therapies.

Keywords: abatacept; anti-TNF therapy; biologics; infection; rheumatoid arthritis; rituximab.

Figure 1

Selection of eligible index hospitalized infections occurring among RA patients while on treatment with anti-TNF therapy

Figure 2

One year infection risk difference between various biologics referent to abatacept Prediction infection risk deciles: Lowest = Decile 1; Median = Decile 5; Highest = Decile 10 Lowest refers to the subcohort of patients at the lowest risk for subsequent infection, from decile 1 of the infection risk score. Median represents the subcohort of patients from decile 5. Highest are the patients from decile 10.

Figure 3

Hazard of subsequent hospitalized infection associated with various biologic therapies ETA = etanercept; INF = infliximab; ADA = adalimumab; ABA = abatacept; RIT = rituximab Note: the y-axis represents the hazard of infection at each day of follow-up.