Serious infections in patients with rheumatoid arthritis and other immune-mediated connective tissue diseases exposed to anti-TNF or rituximab: data from the Spanish registry BIOBADASER 2.0

Abstract

Data on infections in patients exposed to biologic therapies are mainly focused on rheumatoid arthritis (RA). Little is known about the safety profile in other immune-mediated connective tissue diseases (ICTD). The purpose of this study was to describe and to compare the risk of serious infections (SI) in patients with RA and other ICTD on anti-TNF or rituximab and to identify predictors of SI. We analyzed RA or other ICTD patients on anti-TNF or rituximab included in the Spanish registry BIOBADASER 2.0 (2000-2011). For each disease group, incidence rate (IR), mortality rate (MR) and IR ratio (IRR) of SI with 95% CI were estimated. Risks were then standardized by age and sex to the general population. Risk factors for SI were assessed by Poisson regression models. A total of 3,301 patients on anti-TNF (n = 3,166) or rituximab (n = 135), of which 176 (5%) had ICTD other than RA, were analyzed. IR of SI was higher in non-RA ICTD than in RA, with an IRR of 3.15 (95% CI 1.86, 5.31) before adjustment and 1.96 (95% CI 1.06, 3.65) after adjustment for age, comorbidity and corticoid use. Mortality due to infections was higher in ICTD although it did not reach statistical significance. Age, disease duration, comorbidities, corticosteroids and ICTD different to RA were all independently associated with SI. Patients with ICTD other than RA are at a high risk of SI when prescribed anti-TNF or rituximab, partly due to the excess comorbidity and immunosuppressive co-treatment, but also to the inflammatory disease. When evaluating the risk/benefit ratio of off-label medications in ICTD patients, age, comorbidities and corticoid use should carefully be taken into account, applying adequate preventive measures.

Safety of synthetic and biological DMARDs: a systematic literature review informing the 2016 update of the EULAR recommendations for management of rheumatoid arthritis

“…One study comparing bDMARDs with the general population reported standardised incidence rates of 16–20 for tumour necrosis factor-α inhibitor (TNFi) and even higher for RTX (table 1). 15 In total, six studies,21 44–48 performed in European and American datasets, of which four were at low risk of bias, focused on the occurrence of herpes zoster, most of them reporting no increased risk for this type of infection in patients on TNFi (no studies for other bDMARDs), particularly the studies at low risk of bias and/or those that had been adjusted for dropouts 21 44–46…”

Immunologic Biomarkers for Clinical and Therapeutic Management of Psoriasis

“…Regarding the potential influence of anti-TNF- α -based therapy on the setting of adaptive immune functional responses against viral and bacterial antigens, previous reports in different inflammatory diseases, including psoriasis and psoriatic arthritis, rheumatoid arthritis, spondyloarthritis, and Crohn's disease, showed that most common adverse events are represented by the occurrence of infections and by an unexpected high frequency of reactivation of latent tuberculosis infections (LTB), which are often severe and characterized by extrapulmonary and disseminated lesions [58]. …”

Acute Respiratory Events in Connective Tissue Disorders

“…Coadministration of biological factors or a combination of these therapies with high doses of corticosteroids multiplies the risk of infection and should definitively be avoided, especially in elderly patients with lung comorbidities. On the other hand, upon a developed lung infection, discontinuation of immunosuppression does not lead to precipitous reconstitution of the immune system [55,65,66,67,68,69,70,71]. All the above parameters significantly increase the risk of bacterial, mycobacterial, viral, and fungal pulmonary infections in CTD patients (fig.…”