Interleukin-1 Inhibitors Show Excellent Retention Rates in sJIA Patients

Interleukin-1 Inhibitors Show Excellent Retention Rates in sJIA Patients

Sobi‘s Kineret (anakinra) and Novartis‘ Ilaris (canakinumab), two interleukin-1 inhibitors that have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of systemic onset juvenile arthritis (sJIA), showed excellent retention rates, especially during the first year of treatment, a study reports.

The study, “Drug Retention Rate and Predictive Factors of Drug Survival for Interleukin-1 Inhibitors in Systemic Juvenile Idiopathic Arthritis,” was published in Frontiers in Pharmacology.

sJIA is the most severe type of juvenile arthritis (JIA) and is characterized by widespread tissue inflammation that not only affects patients’ joints, but also organs and glands.

Previous studies have shown that tissue inflammation in sJIA patients is mainly driven by the excess production of interleukin-1/6/18 (IL-1, IL-6 and IL-18) immune system molecules.

For this reason, sJIA treatment options have centered on the development of therapies that can inhibit the function of these molecules, reducing tissue inflammation.

“However, while robust evidence from randomized clinical trials is available in the medical literature, only a small amount of real-life data has been published so far, especially in the context of early treatment, and few of them have marginally investigated anti-IL-1 agents’ drug retention rate (DRR) on a relatively long-term follow-up,” researchers stated.

Retention rate is defined as the proportion of patients who maintain the same therapy in a given time period. It can be used to evaluate the effectiveness and safety of treatments.

In this study, researchers from the University of Siena in Italy set out to characterize the retention rate of Kineret and Ilaris in a group of sJIA patients.

The multicenter, retrospective study focused on analyzing medical records from 77 children with sJIA — 34 boys and 43 girls, average age 12 — who were followed up on at 15 Italian tertiary referral centers between January 2008 and July 2016.

All children enrolled for a total of 86 treatment courses (Kineret was used in 61 regimens, and Ilaris in 25) for an average period of 22.67 months. Twenty-two out of the 77 children were treated in combination with conventional disease-modifying anti-rheumatic drugs (cDMARDs), and another 22 with other biologic therapies.

Results showed excellent drug retention rates for both IL-1 inhibitors at 12, 24, 48, and 60 months of follow-up, with 79.9, 59.5, 53.5, and 53.5% rates of overall survival, respectively). No statistically significant differences in retention rates were found between children treated with Kineret and Ilaris, nor between children treated only with IL-1 inhibitors and those who also received cDMARDS.

Median disease duration and treatment delay were significantly higher among patients who discontinued IL-1 blockers (5.88 years and 3.71 years, respectively) compared to those who continued to be treated with these biologic agents (3.17 years and 1.18 years, respectively).

Conversely, significant differences in retention rates were found between patients who were never treated with biologic agents and those who had previously been treated with them, and when considering the occurrence of adverse events.

Only 13 out of 77 children (17.1%) experienced adverse events (11 on Kineret, two on Ilaris). The most common adverse events were skin reactions at the injection site (seven children), followed by overall skin rashes (four children) and respiratory problems (one child). No serious adverse events occurred in the course of the study.

Further analysis also showed that children previously treated with biologic agents and those who experienced adverse events were more likely to withdraw from treatment with IL-1 inhibitors.

“[O]ur results have shown an excellent overall retention rate of the IL-1 inhibitors [Kineret] and  [Ilaris]. Both IL-1 inhibitors showed a similar [drug retention rate], and their survival was not affected by the concomitant use of cDMARDs. These data highlight the effectiveness of these agents in sJIA patients as monotherapy,” researchers said.

“On the other hand, the retention rate of anti IL-1 agents was influenced by the different line of biologic therapy, suggesting that [Kineret] and [Ilaris] should be used as first-line biologics.”

Researchers believe there is the need “for a timely introduction of modern cytokine-blocking strategies to prevent or at least minimize structural damage due to long-term disease and treatment-related [adverse events].”

These data “highlight the significant impact of treatment delay in [drug retention rate] of IL-1 inhibitors … Early IL-1 blockade may take advantage of the “window of opportunity” and modify disease evolution, while avoiding long-term sequelae which have proven to be detrimental in a limited-resource setting where early diagnosis or access to multidisciplinary care and to biologics are still obstacles to overcome,” they concluded.


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