Efficacy and Safety of Tocilizumab in a Real-Life Observational Cohort of Patients With Polyarticular Juvenile Idiopathic Arthritis

Minna-Maija Grönlund; Terhi Remes-Pakarinen; Liisa Kröger; Kati Markula-Patjas; Maria Backström; Anne Putto-Laurila; Kristiina Aalto; Paula Vähäsalo


Rheumatology. 2020;59(4):732-741. 

In This Article

Abstract and Introduction


Objectives: To evaluate the patterns of usage, efficacy and safety of tocilizumab in polyarticular JIA.

Methods: An observational study of 56 consecutive polyarticular JIA patients was conducted using patient charts and electronic JIA databases. Efficacy was assessed by tocilizumab survival, rates of low disease activity (LDA) and of inactive disease by 10-joint Juvenile Arthritis Disease Activity Score (JADAS-10), and of clinically inactive disease according to Wallace's preliminary criteria. Efficacy and rate of adverse events (AEs) were evaluated during a 24-month period after tocilizumab commencement.

Results: Tocilizumab was started on average as third-line biological agent (median, range first- to fourth-line) at a median disease duration of 5.2 years (interquartile range 3.0–7.7). Survival rates were 82% at 12 months and 64% at 24 months. The reasons for discontinuation were inadequate treatment effect in 50%, AE plus inadequate treatment effect in 37.5% and AE alone in 12.5%. LDA (JADAS-10 ≤3.9) was reached in 58% at 12 months and in 84% at 24 months, inactive disease (JADAS-10 ≤0.7) in 19% and 44%, and clinically inactive disease in 28% and 46%, respectively. The rate of AEs was 200.9/100 patient years and of serious AEs 12.9/100 patient years.

Conclusion: Survival of tocilizumab was high and a large proportion of the treatment-resistant patients reached LDA at 12 months of treatment. The LDA rate continued to increase throughout 24 months. The rates of AEs and serious AEs were higher than in register studies but lower than in the originator study of tocilizumab.


JIA is a heterogeneous collection of diseases categorized into seven subtypes according to the ILAR classification criteria.[1] The majority of children with different subtypes develop a so-called polyarticular course of the disease with inflammation in five or more joints.[2,3] Children with polyarticular JIA (pJIA) have a more treatment-resistant disease than those with fewer joints affected, and they have longer periods of active disease,[3–5] which is associated with higher risk of joint damage.[6] Accordingly, recent treatment recommendations for pJIA suggest starting biological DMARDs (bDMARDs) as initial treatment or after 3–6 months' use of synthetic DMARDs (sDMARDs) with non-response.[7–9] A trend of using bDMARDs earlier in the disease course and in JIA patients with lower disease activity has been detected in several studies.[5,10,11]

Currently approved biological agents for the treatment of pJIA include abatacept, adalimumab, etanercept and tocilizumab (both European Medicines Agency, and Food and Drug Administration) and golimumab (European Medicines Agency). First-line biological agents in the treatment of pJIA have mostly been TNF inhibitors, partly due to the order of approval[11,12] and national regulatory rules.[11]

Tocilizumab, a humanized monoclonal IL-6 receptor antibody, was approved for treatment of pJIA in 2013 as first-line biological agent in the case of inadequate response to MTX (https://www.ema.europa.eu/medicines/human/EPAR/roactemra). According to the German BiKeR study, during 2011–15 tocilizumab was used as first-line biological agent in 18.9% of pJIA patients ever using tocilizumab.[12] Horneff et al.[12] found no difference in the efficacy of adalimumab, etanercept or tocilizumab either as first-line or second-line biological agent in pJIA. Similarly, a meta-analysis of the original withdrawal studies of abatacept, adalimumab, etanercept and tozilicumab in pJIA patients found no difference between these bDMARDs in efficacy of preventing flares or in improving symptoms.[13]

Randomized controlled trials remain the gold standard for establishing the efficacy and short-term safety of new therapeutic agents. However, such studies have strict criteria of patient selection with regard to disease duration and disease severity; in addition, the withdrawal design used in the JIA biological agent studies can overestimate the effect of the trial agent.[14,15] Thus, the results of randomized controlled trials are hard to generalize to real-life clinical practice. Consequently, observational data of unselected real-life patients provides important additional information to complement the results of randomized controlled trials.

Today, there is only limited information from observational studies investigating the use of tocilizumab in JIA patients.[11,12,16] We conducted a nationwide observational study in Finland to detect the patterns of usage, efficacy and safety of tocilizumab in pJIA patients in routine clinical practice.