Background/Purpose: Rituximab is a chimeric monoclonal antibody for the treatment of rheumatoid arthritis (RA). Prolonged B-cell depletion from repeated doses of rituximab may be associated with increased risk of infection during subsequent biologic use; however, there are limited data on rates of infection in patients (pts) with RA who switched to a subsequent biologic following rituximab.^1-3 The objectives of this analysis were to assess whether time between last rituximab infusion and switching to a biologic with a different mechanism of action and intensity of rituximab use influenced risk of infection in a large, national RA pt registry (Corrona).

Methods: Pts with RA who newly initiated rituximab within Corrona were included if they switched to a (non-rituximab) biologic and had ≥ 1 follow-up visit within 12 months of switching. Pts were followed from the time they switched to a subsequent biologic to either the first infectious event or 12 months. The primary outcome was time to the first infectious event. Pts were categorized by the duration of time between their last rituximab infusion and switching to a subsequent biologic (≤ 5 months, 6-11 months and ≥ 12 months). Additionally, the number and rate of rituximab retreatments prior to starting the subsequent biologic were evaluated. Cox regression models estimated the association between time to starting a subsequent biologic and infection, and were adjusted for potential confounders.

Results: A total of 215 pts who switched to a subsequent biologic following rituximab use were included in this analysis (≤ 5 months [N = 104], 6-11 months [N = 67] and ≥ 12 months [N = 44]). Baseline characteristics were similar between the groups except for higher tender joint count and rate of rituximab retreatment in those pts who switched to a subsequent biologic earliest. Fewer than 50% of patients experienced an infection; of those patients who had an infection during the 12-month follow-up, the median (IQR) time to infection was 4 (2, 5) months. The overall rates of infection (95% CI) per person-year were 0.34 (0.22, 0.52), 0.30 (0.17, 0.52) and 0.41 (0.22, 0.77) in the ≤ 5 months, 6-11 months and ≥ 12 months groups, respectively. After adjusting for potential confounders, time to switch to a subsequent biologic was not associated with infection, which remained unchanged when including the number and rate of rituximab retreatments in the models (Table).

Conclusion: Duration of time between last rituximab infusion and switching to a biologic with a different mechanism of action was not associated with an increased rate of infection in pts with RA. Additionally, the number and rate of rituximab retreatments did not influence the risk of infection associated with the subsequent biologic.

References:

1.    Breedveld F, et al. Ann Rheum Dis. 2006;65(Suppl II):178.

2.    Genovese MC, et al. Ann Rheum Dis. 2009;68:1894-7.

3.    Gottenberg J, et al. Ann Rheum Dis. 2010;69(Suppl 3):385.