Treatment of systemic juvenile idiopathic arthritis (sJIA) with either the approved therapy Actemra (tocilizumab) or Kineret (anakinra, not yet approved for sJIA) led to similar effectiveness after one year, according to a new U.K. real-world study.
Nearly half of the patients analyzed achieved minimal disease activity (MDA).
The research, “Short-term outcomes in patients with systemic juvenile idiopathic arthritis treated with either tocilizumab or anakinra,” was published in the journal Rheumatology.
Compared to other disease subtypes, sJIA is characterized by different clinical manifestations, genetic markers, and underlying mechanisms, which include an important role of the innate immune system. This has led to different treatment strategies, including the interleukin (IL)-6 inhibitor Actemra (available as RoActemra in Europe), developed by Genentech, and the IL-1 blockers Kineret (marketed by Sobi) and Ilaris (canakinumab, Novartis). Both IL-1 and IL-6 are pro-inflammatory molecules.
Current recommendations in the U.K. indicate that sJIA patients should be prescribed Actemra or Kineret following treatment failure with the immunosuppressant methotrexate. Only patients with macrophage activation syndrome (MAS), a serious complication of rheumatic diseases, and unresponsive to intravenous steroids should receive first-line treatment with Kineret.
Unlike Actemra, which showed efficacy in clinical trials, evidence on the use of Kineret in JIA is scarce. Although results have shown benefits that include inactive disease following a median of over two years of follow-up, most studies have a small number of patients.
A 2017 study in Germany reported that treatment with either Actemra or an IL-1 blocker (Kineret or Ilaris) led to 27% and 35% of patients, respectively, achieving at least 90% improvement in three or more variables of JIA (ACR Pedi 90). No difference was found in disease activity scores.
Aiming to inform clinicians about the use of these therapies, the scientists compared therapeutic short-term outcomes in U.K. children with sJIA starting either intravenous Actemra or subcutaneous Kineret between 2010 and 2016.
Besides baseline characteristics of all patients and their association with outcomes at one year of treatment, the team compared treatment response, persistence on treatment, and reasons to stop in children starting either therapy.
The three main outcome measures being investigated were proportion of patients achieving MDA, clinically inactive disease (CID), and ACR Pedi 90.
The study used data from the UK’s Biologics for Children with Rheumatic Diseases (BCRD) study, which means that “it is likely that the numbers reported in this analysis were representative of the UK population,” the team stated.
A total of 76 sJIA patients (43 girls, median age 7 — range 3-12) were included, 54 on Actemra and 22 on Kineret.
Of the 53 patients starting treatment with a biologic drug for the first time, 19 were taking Kineret (86% of this group’s total) and 34 Actemra (63%). Most (95%) has been previously treated with methotrexate. Eleven of the 20 Actemra patients (55%) who had been previously treated with a biologic had received an IL-1 inhibitor, while two of the three Kineret patients had received Actemra.
Patients taking Kineret had a median disease duration of one year before starting treatment, while those on Actemra had had sJIA for two years.
At one year of treatment, 42% achieved ACR Pedi 90, 51% MDA, and 39% CID — matching previous reports — with the two medications achieving similar responses. No relation was found with baseline disease characteristics.
“In this real-world cohort of patients with systemic JIA receiving tocilizumab (Actemra) or Kineret (anakinra), approximately half achieved a minimal disease state by one year,” the researchers wrote.
Persistence on treatment at one year was better with Actemra than with Kineret (89% vs. 59%).
Fifteen patients (20%) discontinued by one year, one due to remission (Kineret), six due to inefficacy (four Kineret, two Actemra), seven due to adverse events — three on Actemra (rash, reduced levels of neutrophils, active MAS), four on Kineret (stomach cramps and diarrhea, injection site reaction, difficulty with daily injection), and one stopped Actemra for unknown reasons.
The team concluded that “treatment responses appeared similar between the two biologic therapies.”
The team also emphasized the fact that “anakinra [Kineret] being used first-line in some patients, despite the availability of tocilizumab [Actemra], may reflect clinicians’ preferences based on clinical scenarios and this needs further exploration.”
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