Incidence of Infectious Adverse Events in Patients With Rheumatoid Arthritis and Spondyloarthritis on Biologic Drugs—Data From the Brazilian Registry for Biologics Monitoring

Abstract

Background The safety profile of biologic drugs might present substantial regional differences. Since 2009, the Brazilian Society of Rheumatology has maintained BIOBADABRASIL (Brazilian Registry for Biologic Drugs), a registry for monitoring of biologic therapies in rheumatic diseases. Objectives The aim of this study was to verify the incidence rate (IR) of serious infections in rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients on biologic drugs. Methods BIOBADABRASIL prospectively included patients with rheumatic diseases who started the first biologic drug or a synthetic disease-modifying antirheumatic drug as a parallel control group. This study focuses on serious infectious adverse events (SIAEs) in RA and SpA patients on biologic drugs compared with controls, from January 2009 to June 2015. Time of exposure was set from initiation of the drug to the date of last administration or censorship. Serious infectious adverse events IR was calculated per 1000 patient/years with 95% confidence interval (CI). Results A total of 1698 patients (RA, 1121; SpA, 577) were included, 7119 patient/years. Serious infectious adverse events were more common among patients on tumor necrosis factor inhibitors (TNFi's) than controls (adjusted IR ratio, 2.96 [95% CI, 2.01–4.36]; p < 0.001). Subsequent TNFi was associated with a higher SIAEs incidence when compared with first TNFI (adjusted IR ratio, 1.55 [95% CI, 1.15–2.08]; p = 0.004). Serious infectious adverse events were associated with age and corticosteroids intake. Serious infectious adverse events were more frequent in the respiratory tract in all subgroups. Conclusions In BIOBADABRASIL, biologic drugs, especially the subsequent TNFi, were associated with a higher risk of serious infections compared with synthetic DMARDs. Corticosteroid intake and age represented risk factors for SIAEs. Constant monitoring is required to follow the safety profile of drugs in the clinical setting of rheumatic conditions in Brazil.

Safety of synthetic and biological DMARDs: a systematic literature review informing the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis

“…Of the 42 observational studies, 16 addressed the risk of infections in patients receiving bDMARDs (3 also included patients on tofacitinib),10–25 8 studies focused on malignancies,16 26–32 with all except one (comparing MTX to the general population),27 assessing patients on bDMARDs. The risk of MACEs was evaluated in 10 studies, all performed in patients treated with bDMARDs,16 33–41 with one also including patients on tofacitinib 33.…”

“…Out of 16 studies addressing the risk of infections, 3 compared bDMARDs with csDMARDs,10 21 25 and 13 compared the risk across bDMARDs (table 1 and online supplementary tables S2–S31). 11–20 22–24 Three of these studies also compared tofacitinib with bDMARDs 14 17 18…”

“…Two studies have shown an increased risk of SIs both with tumour necrosis factor inhibitor (TNFi) (adjusted incidence rate ratio (aIRR) 3.1; p<0.001; one study at moderate RoB)12 and non-TNFi (aIRR 3.9 (95% CI 1.2; 24.3); one study at high RoB)25 compared with csDMARDs. Another study, at moderate RoB, showed that the risk of sepsis (complicating an SI) is lower in patients treated with bDMARDs compared with those on csDMARDs at the time of the SI.…”

Changing rate of serious infections in biologic-exposed rheumatoid arthritis patients. Data from South American registries BIOBADABRASIL and BIOBADASAR

“…Most patients in the csDMARDs, our control group, were on MTX and/or LEF, with 10% on hydroxychloroquine, sulfasalazine, or azathioprine. Based on a previous analysis of BIOBADABRASIL data and South America treatment practices, we estimate that approximately one third of the csDMARDs group had been exposed to a combination of MTX and LEF during the follow-up period [9], in accordance with national guidelines (i.e., before a bDMARD is indicated, a csDMARDs combination should be tried) [10,11].…”

Ankylosing spondylitis and psoriatic arthritis: revisiting screening of latent tuberculosis infection and its follow-up during anti-tumor necrosis factor therapy in an endemic area

“…According to Brazilian guidelines, all patients with AS and PsA recommended for immunobiological treatment were submitted to LTBI screening before initial therapy ( 9 - 13 ). Active infection was excluded by mycobacterial tests when indicated.…”