The investigators also analyzed the specific risk factors associated with development of severe infectious complications among patients with AAV who received rituximab. Baseline predictors of severe infections included higher erythrocyte sedimentation rate (ESR), white blood cell count, higher steroid doses and an IgG decline ≥30%. Concomitant comorbidities, including chronic obstructive pulmonary disease, diabetes and reduced left ventricular ejection fraction/previous myocardial infarction, were identified as risk factors.
The research found that older age, endobronchial involvement, chronic obstructive pulmonary disease and treatment with alemtuzumab before rituximab were independent risk factors for the development of severe infections following rituximab therapy.
Antibiotic prophylaxis with TMP/SMX at different dosages was used in 73 of 192 patients. Its use was associated with reduced risk of infections, according to the investigators. A multivariate logistic regression analysis showed that its use as a prophylactic antibiotic measure had a positive impact on reducing severe infections. Its use significantly reduced time to first significant infection, according to the published data.
In this study, most patients received a 480 mg dose of TMP/SMX on alternate days; other doses included 960 mg on alternate days and 960 mg twice daily. The prophylaxis was stopped in five patients due to hematopoietic complications in three patients, sore mouth in one patient and abnormal liver function test in the remainder, the researchers reported. In general, its use was maintained for 14.67 months.
Dr. Kronbichler says that in his practice patients receive TMP/SMX “until steroids are stopped. TMP/SMX will be discussed with each patient and those who are keen to stop medication are stopping antibiotic prophylaxis, but I recommend staying on TMP/SMX thrice weekly.”
Antibiotic prophylaxis with TMP/SMX was used in 73 of 192 patients. Its use was associated with reduced risk of infections, according to the investigators.
Current Recommendations
European recommendations (European League Against Rheumatism/European Renal Association–European Dialysis and Transplant Association [EULAR/ERA-EDTA]) encourage the use of P. jirovecci prophylaxis to manage patients with AAV who are receiving cyclophosphamide. No firm recommendations exist concerning its use in patients receiving rituximab, although the updated European Medicines Agency label does recommend prophylaxis during and following rituximab, as appropriate, according to Dr. Kronbichler and colleagues’ report. Dr. Kronbichler anticipates changes will be made in a future update of the EULAR/ERA-EDTA recommendations.
The investigators noted uncertainty exists regarding whether patients with AAV who receive rituximab benefit from P. jirovecii prophylaxis, because “little is known about infections in patients with AAV treated with rituximab.” Two studies published in 2010, the RAVE and RITUXVAS trials, found rituximab to be noninferior to cyclophosphamide as first-line treatment for AAV.2,3 Both trials found similar rates of serious side effects between treatment groups. The RITUXVAS trial reported an 18% rate of severe infections in both arms of the trial, but the number of patients presenting with non-severe infections was 18% in the rituximab group vs. 9% in the cyclophosphamide group.
