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. 2017 Nov 22;19(1):256.
doi: 10.1186/s13075-017-1462-2.

Experience with etanercept, tocilizumab and interleukin-1 inhibitors in systemic onset juvenile idiopathic arthritis patients from the BIKER registry

Gerd Horneff  1 , Anna Carina Schulz  2 , Jens Klotsche  3 , Anton Hospach  4 , Kirsten Minden  3 , Ivan Foeldvari  5 , Ralf Trauzeddel  6 , Gerd Ganser  7 , Frank Weller-Heinemann  8 , Johannes Perter Haas  9
Affiliations

Experience with etanercept, tocilizumab and interleukin-1 inhibitors in systemic onset juvenile idiopathic arthritis patients from the BIKER registry

Gerd Horneff et al. Arthritis Res Ther. .

Abstract

Background: Treatment of systemic onset juvenile idiopathic arthritis JIA (sJIA), although dramatically improved, remains a challenge. Experience from clinical practice will be presented using data from the German Biologics register (BiKeR) for evaluation of efficacy and safety of treatment with etanercept (ETA), tocilizumab (TOC) and the interleukin-1 inhibitors anakinra and canakinumab (IL-1i) in sJIA.

Methods: Patients with sJIA documented in the BIKeR register, who were exposed to ETA, TOC or IL-1i were identified. Baseline demographics, clinical characteristics and disease activity parameters have been documented. Efficacy was determined using the JIA-American College of Rheumatology (ACR) response criteria and the Juvenile Disease Activity Score 10 (JADAS10). An intention-to-treat analysis was performed and patients who discontinued due to inefficacy or intolerance were analysed as non-responders. Safety assessments were based on adverse events (AEs) reports.

Results: Since 2000, 245 sJIA patients (50.3% male) exposed to biologic agents have been identified: 143 patients treated with ETA, 71 with TOC and 60 with IL-1i (anakinra 38, canakinumab 22). All patients received systemic steroids for pre-treatment but less frequently with TOC and IL-1i than with ETA for concomitant treatment. At baseline, the ETA cohort had fewer systemic disease manifestations but more active joints. The JIA-ACR 30/50/70/90 response over a period of 24 months was reached more often in the IL-1i and TOC cohort than with ETA. ETA/TOC/IL1i JADAS-remission (JADAS ≤1) was reached in 20%/37%/52%, minimal disease activity (JADAS ≤3.8 in 35%/61%/68% and ACR inactive disease in 24%/33%/56%). As compared to ETA, rates of AEs were significantly higher in the TOC cohort (risk ratio (RR) 5.3/patient-year; p < 0.0001) and serious AE were observed more frequently with TOC (RR 2.5; p < 0.5) and IL1i (2.9; p < 0.01).

Conclusions: A large proportion of patients gained significant response to treatment especially with TOC or IL-1is. After 6 months on treatment, JADAS remission was reached by up to half of patients while up to two thirds reached JADAS minimal disease activity. ETA has been used in the past but it is clearly less effective and its use in systemic JIA has markedly decreased in Germany.

Keywords: Anakinra; Canakinumab; Etanercept; Still’s disease; Systemic onset juvenile idiopathic arthritis; Tocilizumab.

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Conflict of interest statement

Ethics approval and consent to participate

The study was conducted in accordance with the protocol, International Conference for Harmonization (ICH), Good Clinical Practice (GCP), FDA regulations governing clinical study conduct, ethical principles that have their origin in the Declaration of Helsinki, 1996 revision and 2000 revision with subsequent clarifications, and all applicable local regulations. Before the study was initiated, the study protocol, the informed consent form and subject information were submitted for review to the responsible independent ethics committee of the Aerztekammer Nordrhein, Duesseldorf, Germany, reference number 2/2015/7441. Parents/legal guardians signed the informed consent form before any study-related procedures occurred.

Consent for publication

Not applicable.

Competing interests

Gerd Horneff has received research funds, advisory board membership and honorary fees from Abbvie, Pfizer and Roche. Kirsten Minden has received research grants from Abbvie, Pfizer and Roche and honorary fees from Abbvie, Pfizer, Genzyme and Pharm-Allergan. Ivan Foeldvari has received personal fees from Abbvie, Chugai, Novartis and Genzyme. Anton Hospach has received advisory board membership and honoraria from Pfizer, Abbvie and Roche. Schulz AC, Klotsche J, Trauzeddel R, Ganser G., Weller-Heinemann F and Haas JP declare that they have no competing interests.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Juvenile Disease Activity Score 10 (JADAS-10) remission (defined as JADAS ≤1) and JADAS minimal disease activity (defined as JADAS ≤3.8). The number of patient contributing to the calculation is given below the figure. TOC, tocilizumab; ETA, etanercept; IL-1i, interleukin-1 inhibitor; ACR, American College of Rheumatology
Fig. 2
Fig. 2
Juvenile Disease Activity Score (JADAS)-remission (JADAS-10 ≤ 1) and American College of Rheumatology (ACR) inactive disease (Wallace criteria) in patients in the tocilizumab cohort (a) and the interleukin-1 inhibitor (IL-1i) cohort (b) split according to disease duration <1 year and >1 year. At the last report in the early-treated cohort, 18 patients (75%) on tocilizumab and 16 (80%) on Il-1-inhibitors reached JADAS-remission significantly more frequently (OR 3.9 (95% CI, 1.3–11.6); p = 0.012 for tocilizumab and OR 6.6 (95% CI, 1.8–23.7; p = 0.002 for IL-1i) compared to 20 (44%) and 14 (38%), respectively. No difference was noted in the rate of patients reaching ACR inactive disease. Data are expressed as observed. The number of patients contributing to the calculation is given below the figure
Fig. 3
Fig. 3
Last documented response for the tociizumab (TOC) cohort (a), combined IL-1 inhibitor (IL-1i) cohort (b), canakinumab cohort (c) and anakinra (ANA) cohort (d). The rate of patients with no active joints, no fever, Juvenile Disease Activity Score (JADAS)-remission, American College of Rheumatology (ACR)-defined inactive disease, ACR-remission is given, respectively, in the total cohort and for biologic-naive and pre-exposed patients. Differences in rates were calculated using the chi-square-test. Pearson’s p value is outlined if < 0.05. ETA, etanercept
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