Risk of serious infections in patients with rheumatoid arthritis treated in routine care with abatacept, rituximab and tocilizumab in Denmark and Sweden

Abstract

ObjectiveTo estimate (1) crude and age-and gender-adjusted incidence rates (IRs) of serious infections (SI) and (2) relative risks (RR) of SI in patients with rheumatoid arthritis (RA) initiating treatment with abatacept, rituximab or tocilizumab in routine care.MethodsThis is an observational cohort study conducted in parallel in Denmark and Sweden including patients with RA in Denmark (DANBIO) and Sweden (Anti-Rheumatic Treatment in Sweden Register/Swedish Rheumatology Quality Register) who started abatacept/rituximab/tocilizumab in 2010–2015. Patients could contribute to more than one treatment course. Incident SI (hospitalisations listing infection) and potential confounders were identified through linkage to national registries. Age- and gender-adjusted IRs of SI per 100 person years and additionally adjusted RRs of SI during 0–12 and 0–24 months since start of treatment were assessed (Poisson regression). Country-specific RRs were pooled using inverse variance weighting.ResultsWe identified 8987 treatment courses (abatacept: 2725; rituximab: 3363; tocilizumab: 2899). At treatment start, rituximab-treated patients were older, had longer disease duration and more previous malignancies; tocilizumab-treated patients had higher C reactive protein. During 0–12 and 0–24 months of follow-up, 456 and 639 SI events were identified, respectively. The following were the age- and gender-adjusted 12-month IRs for abatacept/rituximab/tocilizumab: 7.1/8.1/6.1 for Denmark and 6.0/6.4/4.7 for Sweden. The 24-month IRs were 6.1/7.5/5.2 for Denmark and 5.6/5.8/4.3 for Sweden. Adjusted 12-month RRs for tocilizumab versus rituximab were 0.82 (0.50 to 1.36) for Denmark and 0.76 (0.57 to 1.02) for Sweden, pooled 0.78 (0.61 to 1.01); for abatacept versus rituximab 0.94 (0.55 to 1.60) for Denmark and 0.86 (0.66 to 1.13) for Sweden, pooled 0.88 (0.69 to 1.12); and for abatacept versus tocilizumab 1.15 (0.69 to 1.90) for Denmark and 1.14 (0.83 to 1.55) for Sweden, pooled 1.13 (0.91 to 1.42). The adjusted RRs for 0–24 months were similar.ConclusionFor patients starting abatacept, rituximab or tocilizumab, differences in baseline characteristics were seen. Numerical differences in IR of SI between drugs were observed. RRs seemed to vary with drug (tocilizumab < abatacept < rituximab) but should be interpreted with caution due to few events and risk of residual confounding.

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…”

High rates of severe disease and death due to SARS-CoV-2 infection in rheumatic disease patients treated with rituximab: a descriptive study

“…Several studies have described the effect of rituximab on the B cell cytokine network, mainly on B effector and B regulator cells, with a secondary influence on T helper cell response [21,22]. Some studies have reported a higher risk of infection in RA patients treated with rituximab than those treated with other biologic DMARDs [23,24] but these data come from registries and retrospective studies, which may contain bias due to their observational designs. The effects of rituximab on the immune system response to SARS-CoV-2 infection have yet to be elucidated.…”

Understanding the Role of Interleukin-6 (IL-6) in the Joint and Beyond: A Comprehensive Review of IL-6 Inhibition for the Management of Rheumatoid Arthritis

“…In addition to the insights from these postmarketing studies, a number of real-world and registry-based studies provide additional insight into the safety profile of these agents in the wider population of patients with RA. While data from some registries have suggested an increased risk of infections, including serious infections, with agents that inhibit IL-6 signaling [244][245][246][247], a comparative head-to-head analysis of the safety of tocilizumab and TNF inhibitors in the Japanese REAL registry did not find a higher risk for serious adverse events or serious infections with tocilizumab compared with TNF inhibitors after adjustment for potentially confounding factors. The use of oral corticosteroids in patients receiving tocilizumab, however, was a significant risk factor for both serious adverse events and serious infections [248].…”