Long-term use of biologic therapies in people with systemic-onset juvenile idiopathic arthritis (sJIA) is acceptably safe, with varying rates of infections and macrophage activation syndrome depending on choice of medication, a large study has found.
The study, “Long-term surveillance of biologic therapies in systemic-onset juvenile idiopathic arthritis: data from the German BIKER registry,” was published in the journal Rheumatology.
sJIA is a severe type of the disease that accounts for about 10% of JIA cases. Unlike other JIA forms, autoinflammatory processes (when immune cells attack the body’s own tissue) play a central role in sJIA, particularly the molecules interleukin-1 (IL-1) and IL-6.
Clinical trials have shown that biologic therapies that specifically target IL-1 and IL-6 resolved symptoms without relapses in about one-third of sJIA patients. Early IL-1 blocking showed a high response rate and is now recommended as a consensus treatment by the American College of Rheumatology.
Three such therapies are Sobi‘s Kineret (anakinra) and Novartis‘ Ilaris canakinumab), which target IL-1, and Genentech‘s Actemra (tocilizumab), which blocks IL-6. Previously, Amgen‘s Enbrel (etanercept), a biologic that targets the pro-inflammatory protein TNF-alpha, was prescribed commonly for active sJIA, but without satisfactory responses.
While clinical trials have generated data regarding the safety and side effects associated with these therapies, information about adverse events following long-term treatment, especially rare events, is lacking.
To address this gap, researchers in Germany analyzed the long-term safety of biologic therapies in a large group of sJIA patients, identified from the German Biologics JIA Registry (BIKER). That database has been collecting information on people with JIA on biologics since 2001.
Patients were assessed at the beginning of treatment, after three and six months, and every six months thereafter. After treatment stopped, they also were assessed every six months. The mean overall follow-up time was 4.3 years.
A total of 260 patients with sJIA were selected for analysis. Of these, 151 received Enbrel, 109 were given Actemra, 71 took Kineret, and 51 were treated with Ilaris.
People receiving only one treatment course accounted for most (53%, 137 patients) of the group. The choice of biologic therapy changed over time. Before 2006, 87% of patients received Enbrel, which was reduced to only 5% after 2013. Equal numbers of patients were treated with the IL-6 blocker Actemra (46.6%) or the IL-1 blockers Kineret and Ilaris (48.6%).
Safety assessments were based on any adverse side effects reported after the first dose and continued until 90 days after the final dose.
Results showed 464 adverse events (AEs) and 92 serious or life-thereatening adverse events (SAEs), with the highest rates for both AEs and SAEs in those who received Ilaris and Actemra. Significantly higher SAEs rates occurred in people treated with a combination of systemic steroids and Enbrel or Actemra, compared to those not taking steroids.
Likewise, more infectious AEs occurred in patients treated with a combination of steroids and Acterma compared to those without steroids, Meanwhile, the risk for serious, opportunistic infections was significantly higher in those taking Kineret. In turn, Actemra was associated with the highest frequency of liver problems.
Macrophage activation syndrome (MAS) — characterized by over-activation of immune cells called macrophages that leads to fever, organ enlargement, and blood and neurological problems — occurred in all groups. The highest rates were found in patients treated with Ilaris and Actemra.
Three patents had confirmed malignancies, two with Hodgkin’s lymphoma and one with acute myeloid leukemia. Two patients died, one who had a very severe course of sJIA and the other with a recent diagnosis of MAS. They were taking, or had been treated, with Enbrel. Neither death was deemed related to the biologic therapy.
Overall, tolerance of the different treatments was acceptable, the scientists said.
“[T]he data are valuable and provide enhanced knowledge on safety of different biologics for physicians treating soJIA patients,” they wrote.
Still, more studies are needed “to estimate the influence of different biologics or the underlying disease on the occurrence of certain events,” the investigators stated.