Examining Risk for Severe Infection in Rituximab-Treated AAV

Approximately one-quarter of rituximab-treated patients with antineutrophil cytoplasm antibody-associated vasculitis (AAV) developed severe infections over a 2-year observational period, while the use of trimethoprim-sulfamethoxazole prophylaxis reduced this risk, according to results published in the Annals of the Rheumatic Diseases.

The investigators sought to evaluate risk factors for the development of severe or life-threatening infections in rituximab-treated patients with AAV. A total of 192 individuals with AAV from 2 tertiary care specialist centers were identified for inclusion in the study. Severe infections were classified as grade ≥3, according to the Common Terminology Criteria for Adverse Events V4.0.

Overall, 95 severe infections were reported in 25.52% of patients with AAV, which corresponded to an event rate of 26.06 infections per 100 person-years. Of the observed infections, 25% occurred during the first 4 months of follow-up, whereas 50% and 80% were reported after 12 and 18 months, respectively. Antibiotic prophylaxis with trimethoprim-sulfamethoxazole was administered in 38.02% of patients.

Respiratory tract infections (RTIs) were the most common infectious complication (n=63), followed by urinary tract infections (n=12), gastrointestinal tract infections (n=8), mastoiditis/otitis externa infections (n=4), skin infections (n=3), sepsis/septicemia with unidentified site of infection (n=1), catheter-associated exit site infection (n=1), orbital mass infection (n=1), lacrimal gland abscess (n=1), and eye infection (n=1).

The prophylactic use of trimethoprim-sulfamethoxazole was associated with a lower frequency of severe infections (hazard ratio [HR], 0.30; 95% CI, 0.13-0.69). In contrast, older age (HR, 1.03; 95% CI, 1.01-1.05), endobronchial involvement (HR, 2.21; 95% CI, 1.14-4.26), presence of chronic obstructive pulmonary disease (HR, 6.30; 95% CI, 1.08-36.75), and prior alemtuzumab use (HR, 3.97; 95% CI, 1.50-10.54) all increased the risk for severe infections.

When the analysis was limited to RTIs, which represented 66.3% of all infections, endobronchial involvement (HR, 4.27; 95% CI, 1.81-10.06), severe bronchiectasis (HR, 6.14; 95% CI, 1.18-31.91), higher neutrophil count (HR, 1.19; 95% CI, 1.06-1.33), and major relapse (HR, 3.07; 95% CI, 1.30-7.23) as indications for rituximab use conferred a higher risk for infections, whereas refractory disease (HR, 0.25; 95% CI, 0.07-0.90) as an indication for rituximab use was associated with a lower rate of severe infections.

The investigators concluded that although the results of this analysis warrant confirmation in additional studies, they do support the routine use of trimethoprim-sulfamethoxazole in rituximab-treated individuals with AAV.

Disclosures: AK has received travel support from Roche/Genentech. DRWJ has received research grants and consulting fees from Roche/Genentech and Terumo BCT and is supported by the Cambridge Biomedical Research Centre.

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Reference

Kronbichler A, Kerschbaum J, Gopaluni S, et al. Trimethoprim-sulfamethoxazole prophylaxis prevents severe/life-threatening infections following rituximab in antineutrophil cytoplasm antibody-associated vasculitis [published online June 27, 2018]. Ann Rheum Dis. doi:10.1136/annrheumdis-2017-212861