Tocilizumab, IL-1 inhibitors yield 'significant response' for systemic juvenile idiopathic arthritis

Gerd Horneff

A large segment of patients with systemic onset juvenile idiopathic arthritis experienced a significant response to treatment with tocilizumab or the interleukin-1 inhibitors anakinra and canakinumab, according to study findings published in Arthritis Research & Therapy.

In addition, after 6 months of treatment, Juvenile Arthritis Disease Activity Score 10 (JADAS10) remission was reached by half of patients, and up to two-thirds of patients achieved minimal disease activity.

“Patients with systemic onset [juvenile idiopathic arthritis (JIA)] often show a severe treatment resistant disease course,” Gerd Horneff, MD, lead author and head of paediatrics at the Asklepios Children's Hospital, in Sankt Augustin, Germany, told Healio Rheumatology. “Pharmacomedical treatment with biologics is instituted in case with refractory disease. However, Data out of clinical practice is scarce in these patients.”

To evaluate the efficacy and safety of treatment with etanercept, tocilizumab and the interleukin-1 inhibitors anakinra and canakinumab in systematic onset JIA, the researchers analyzed data in the German BIKeR register, which provides surveillance of patients exposed to biologics and thus can identify improvement as well as risks of therapy, Horneff said. They identified 143 patients with systematic onset JIA documented in the BIKeR register who had been treated with etanercept, tocilizumab or interleukin-1 inhibitors since 2000, and recorded baseline demographics, clinical characteristics and disease activity parameters.

The researchers determined efficacy using the JIA-ACR response criteria, as well as the JADAS10. They then performed an intention-to-treat analysis, with patients who ended treatment due to inefficacy or intolerance categorized as nonresponders. The researchers’ safety assessments were based on adverse events reports. Among the participants, 143 had been treated with etanercept, 71 with tocilizumab and 60 with interleukin-1 inhibitors — 38 with anakinra and 22 with canakinumab.

According to the researchers, the etanercept group at baseline had fewer systemic disease manifestations, but more active joints. Efficacy, determined through the JIA-ACR 30/50/70/90, throughout 24 months was reached more often in the interleukin-1 inhibitor and tocilizumab groups than with the etanercept cohort. In addition, JADAS-remission, defined as JADAS 1, was reached in 20% of the etanercept group, 37% of the tocilizumab group and 52% of the interleukin-1 inhibitor group. Minimal disease activity (JADAS 3.8) was reached in 35% of etanercept patients, 61% of tocilizumab patients and 68% interleukin-1 inhibitors patients. Adverse event rates were significantly higher in the tocilizumab cohort (RR = 5.3/patient-year; P<0.0001) compared with the etanercept group, and serious adverse events were observed more frequently with tocilizumab (RR = 2.5; P<0.01) and interleukin-1 inhibitors (RR = 2.9; P<0.01).

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“With this paper, a marked improvement of efficacy was noted with the introduction of IL-1 and Il-6 inhibitor to treatment,” Horneff said. “Before, refractory systemic onset JIA patients were treated with TNF-inhibitors. Thus, those patients who also presented with a severe phenotype could serve as a historic control group.”

According to Horneff, patients who were treated earlier more often responded to said treatment.

“In conclusion, remission is an achievable goal for patients with systemic JIA,” he said. “Treatment with biologics targeting Il-1 or Il-6 should be initiated in refractory disease early during the disease course.” – by Jason Laday

Disclosure: Horneff reports research grants, advisory board membership and honorary fees from Abbvie, Pfizer and Roche. See the full study for additional author disclosures.

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Source:

Horneff G, et al. Arthritis Res Ther. 2017; doi:10.1186/s13075-017-1462-2.