Identifier to cite or link to this item: http://hdl.handle.net/20.500.13003/13391
Rates of, and risk factors for, severe infections in patients with systemic autoimmune diseases receiving biological agents off-label
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DOI: 10.1186/ar3397
ISSN: 1478-6354
WOS ID: 000297150200003
Scopus EID: 2-s2.0-79960055269
PMID: 21745378
Embase PUI: L51521432
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Diaz-Lagares, Candido; Perez-Alvarez, Roberto; Garcia-Hernandez, Francisco J.; Ayala-Gutierrez, Maria M.; Luis Callejas, Jose; Martinez-Berriotxoa, Agustin; Rascon, Javier; Caminal-Montero, Luis; Selva-O'Callaghan, Albert; Oristrell, Joaquim; Hidalgo, Carmen; Gomez-de-la-Torre, Ricardo; Saez, Luis; Canora-Lebrato, Jesus; Camps, Maria-Teresa; Ortego-Centeno, Norberto; Castillo-Palma, Maria-Jesus; Ramos-Casals, Manuel; BIOGEAS Study GrpPublication date
2011Document type
research articleCitation
Diaz-Lagares C, Perez-Alvarez R, Garcia-Hernandez FJ, Ayala-Gutierrez MM, Callejas JL, Martinez-Berriotxoa A, et al. Rates of, and risk factors for, severe infections in patients with systemic autoimmune diseases receiving biological agents off-label. Arthritis Res Ther. 2011;13(4):R112.Abstract
Introduction: The purpose of this observational study was to analyze the rates, characteristics and associated risk factors of severe infections in patients with systemic autoimmune diseases (SAD) who were treated off-label with biological agents in daily practice. Methods: The BIOGEAS registry is an ongoing Spanish prospective cohort study investigating the long-term safety and efficacy of the off-label use of biological agents in adult patients with severe, refractory SAD. Severe infections were defined according to previous studies as those that required intravenous treatment or that led to hospitalization or death. Patients contributed person-years of follow-up for the period in which they were treated with biological agents. Results: A total of 344 patients with SAD treated with biological agents off-label were included in the Registry until July 2010. The first biological therapies included rituximab in 264 (77%) patients, infliximab in 37 (11%), etanercept in 21 (6%), adalimumab in 19 (5%), and 'other' agents in 3 (1%). Forty-five severe infections occurred in 37 patients after a mean follow-up of 26.76 months. These infections resulted in four deaths. The crude rate of severe infections was 90.9 events/1000 person-years (112.5 for rituximab, 76.9 for infliximab, 66.9 for adalimumab and 30.5 for etanercept respectively). In patients treated with more than two courses of rituximab, the crude rate of severe infection was 226.4 events/1000 person-years. A pathogen was identified in 24 (53%) severe infections. The most common sites of severe infection were the lower respiratory tract (39%), bacteremia/sepsis (20%) and the urinary tract (16%). There were no significant differences relating to gender, SAD, agent, other previous therapies, number of previous immunosuppressive agents received or other therapies administered concomitantly. Cox regression analysis showed that age (P = 0.015) was independently associated with an increased risk of severe infection. Survival curves showed a lower survival rate in patients with severe infections (log-rank and Breslow tests < 0.001). Conclusions: The rates of severe infections in SAD patients with severe, refractory disease treated depended on the biological agent used, with the highest rates being observed for rituximab and the lowest for etanercept. The rate of infection was especially high in patients receiving three or more courses of rituximab. In patients with severe infections, survival was significantly reduced. Older age was the only significant predictive factor of severe infection.
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https://dx.doi.org/10.1186/ar3397Keywords
Infection raterituximab
infliximab
etanercept
adalimumab
systemic lupus erythematosus
Sjogren syndrome
vasculitis
MeSH
Autoimmune DiseasesAged, 80 and over
Aged
Biological Products
Kaplan-Meier Estimate
Young Adult
Adult
Humans
Adolescent
Middle Aged
Male
Female
Risk Factors
Proportional Hazards Models
Off-Label Use
DeCS
Modelos de Riesgos ProporcionalesFemenino
Adolescente
Masculino
Factores de Riesgo
Humanos
Persona de Mediana Edad
Adulto Joven
Estimación de Kaplan-Meier
Anciano
Anciano de 80 o más Años
Productos Biológicos
Enfermedades Autoinmunes
Adulto
Uso Fuera de lo Indicado