Comparative risk of infections among real-world users of biologics for juvenile idiopathic arthritis: data from the German BIKER registry

Abstract

To examine whether treatment with interleukin (IL)-1-, IL-6-, tumour necrosis factor α (TNFα)-inhibitors or Abatacept is associated with an increased risk of common infections, infections requiring hospitalization (SAE) or opportunistic infections among real-world juvenile idiopathic arthritis (JIA) patients. Furthermore, the influence of other patient-related covariates on the occurrence of infections was investigated. Patients diagnosed with JIA and treated with biologics were selected from the German BIKER registry. Incidence rates (IR) of infections per 100 person years were calculated and compared between the different cohorts. Using multivariate logistic regression, odds ratios with 95% confidence intervals (CI) were determined for the influence of patient-related covariates (age, diagnosis, laboratory data, concomitant medication, JIA activity, comorbidities, and premedication) on the occurrence of infections. 3258 patients entered the analysis. A total of 3654 treatment episodes were distributed among TNFα- (Etanercept, Adalimumab, Golimumab, Infliximab, n = 3044), IL-1- (Anakinra, Canakinumab, n = 105), IL-6- (Tocilizumab, n = 400) and T-cell activation inhibitors (Abatacept, n = 105). 813 (22.2%) patients had at least one infection, 103 (2.8%) patients suffered from an SAE infection. Both common and SAE infections were significantly more frequent in IL-1 (IR 17.3, 95% CI 12.5/24 and IR 4.3, 95% CI 2.3/8.3) and IL-6 cohort (IR 16.7, 95% CI 13.9/20 and IR 2.8, 95% CI 1.8/4.4) compared to TNFα-inhibitor cohort (IR 8.7, 95% CI 8.1/9.4 and IR 1, 95% CI 0.8/1.3). When comparing the influencing factors for various infectious diseases, the use of corticosteroids, younger age, cardiac comorbidities and higher JIA-activity are the most striking risk factors. Relative to TNFα inhibitors and Abatacept, IL-1 and IL-6 inhibitors were associated with an increased risk of common and SAE infections. The influencing covariates identified may be helpful for the choice of a suitable biologic to treat JIA.

Efficacy and Safety of Etanercept Biosimilars Compared With the Originator for Treatment of Juvenile Arthritis: A Prospective Observational Study

“…The data used for this study were collected within the framework of the German BIKER registry. This prospective, observational registry has existed since 2001 and has already been described in various publications ( 13 , 14 , 15 ). “BIKER” is an acronym in the German language and stands for “Biologics in Paediatric Rheumatology Registry.” The registry is covering the whole of Germany, with more than 80 participating pediatric rheumatology units and may, therefore, be representative not only for Germany but for a number of comparable countries.…”

“…The data used for this study were collected within the framework of the German BIKER registry. This prospective, observational registry has existed since 2001 and has already been described in various publications (13)(14)(15). "BIKER" is an acronym in the German language and stands for "Biologics in Paediatric Rheumatology Registry."…”

Position statement of the Spanish Society of Pediatric Rheumatology on infection screening, prophylaxis, and vaccination of pediatric patients with rheumatic diseases and immunosuppressive therapies: Part 1 (screening)

“…Like adults, pediatric patients with immune-mediated rheumatic diseases are at an increased risk of infections [2]. With current aggressive treatment strategies incorporating the early use of immunosuppressive therapies like biological drugs, susceptibility to infections, including opportunistic ones, increases further [3]. Besides, it is important to bear in mind that during the first years of life children are being vaccinated, and that the immunogenicity of vaccinations may be reduced because of the immunosuppressed status of these patients, thereby further increasing the infection risk [2].…”

A randomized, double-blind, placebo-controlled 12-week trial of infliximab in patients with juvenile-onset spondyloarthritis

“…In contrast, a trial of infliximab in 122 patients with polyarticularcourse juvenile rheumatoid arthritis randomized to 3 mg/kg or 6 mg/kg yielded AEs in 95% of the patients [18,19], including serious AEs in 32% of infliximab users. The Pharmachild (n = 2022; all licensed bDMARDs) and Biker (n = 1697; all licensed bDMARDs) registries barely mention the use of infliximab suggesting low utilization of this TNFi in the paediatric population in some countries [45][46][47][48][49]. Interestingly, few AEs have been reported with the use of high doses of infliximab in refractory cases of JIA extra-musculoskeletal manifestations such as uveitis [50,51].…”