Fungal infections following treatment with monoclonal antibodies and other immunomodulatory therapies.

Tumor necrosis factor (TNF) is a proinflammatory cytokine involved in a wide range of important physiologic processes and has a pathologic role in some diseases. TNF antagonists (infliximab, adalimumab, etanercept) are effective in treating inflammatory conditions. Antilymphocyte biological agents (rituximab, alemtuzumab), integrin antagonists (natalizumab, etrolizumab and vedolizumab), interleukin (IL)-17A blockers (secukinumab, ixekizumab) and IL-2 antagonists (daclizumab, basiliximab) are widely used after transplantation and for gastroenterological, rheumatological, dermatological, neurological and hematological disorders. Given the putative role of these host defense elements against bacterial, viral and fungal agents, the risk of infection during a treatment with these antagonists is a concern. Fungal infections, both opportunistic and endemic, have been associated with these biological therapies, but the causative relationship is unclear, especially among patients with poor control of their underlying disease or who are undergoing steroid therapy. Potential recipients of these drugs should be screened for latent endemic fungal infections. Cotrimoxazole prophylaxis could be useful for preventing Pneumocystis jirovecii infection in patients over 65 years of age who are taking TNF antagonists, antilymphocyte biological agents or who have lymphopenia and are undergoing concomitant steroid therapy. As with other immunosuppressant drugs, TNF antagonists and antilymphocyte antibodies should be discontinued for patients with active infectious disease.

Indicator opportunistic infections after biological treatment in rheumatoid arthritis, 10 years follow-up in a real-world setting.

BACKGROUND: This research describes the incidence and factors associated with opportunistic infections in rheumatoid arthritis (RA) patients treated with biological disease-modifying antirheumatic drugs (bDMARDs). METHODS: A retrospective longitudinal study was carried out from 2007 to 2018. We included RA patients treated with a tumor necrosis factor (TNF)-targeted bDMARD or non-TNF-targeted bDMARD from the start of bDMARDs. An independent variable was the development of an indicator of opportunistic infection after biological (IOIb) treatment. Secondary variables included sociodemographic, clinical, and treatments. We used survival techniques to estimate the incidence of IOIb, per 1000 patient-years (95% CI). We performed a Cox multivariate regression analysis model to compare the risk of IOIb. Results were expressed as a hazard ratio (HR). RESULTS: A total of 441 RA patients were included, that started 761 different courses of bDMARDs. A total of 81% were women with a mean age at first bDMARD of 57.3 ±â€„14 years. A total of 71.3% of the courses were TNF-targeted bDMARDs and 28.7% were non-TNF-targeted bDMARDs. There were 37 IOIb (25 viral, 6 fungal, 5 bacterial, 1 parasitic). Nine of these required hospitalization and one died. The global incidence of IOIb was 23.2 (16.8-32). TNF-targeted bDMARDs had 25 IOIb, incidence 20.5 (13.9-30.4), and non-TNF-targeted bDMARDs had 12 IOIb, incidence 31.7 (18-55.9). In the multivariate analysis, glucocorticosteroids (HR 2.17, p = 0.004) and lower lymphocyte count increased the risk for IOIb (HR 0.99, p = 0.005). CONCLUSIONS: The incidence of IOIb due to bDMARDs was 23 cases per 1000 patient-years. Close monitoring should be taken in the RA patients treated with bDMARDs and glucocorticosteroids, mainly in elderly patients and those with a low total lymphocyte count at the beginning of bDMARD treatment.