An immunosuppressive medication, anakinra appears effective in treating secondary hemophagocytic lymphohistiocytosis (sHLH) in children, particularly when patients have underlying rheumatic disease and no evidence of cancer.
The study, “Benefit of Anakinra in Treating Pediatric Secondary Hemophagocytic Lymphohistiocytosis,” was published in the journal Arthritis & Rheumatology.
HLH is a rare, life-threatening disease, in which certain white blood cells turn on a patient’s body, causing excessive inflammation. It can be inherited through genetic mutations (primary HLH), or triggered by a number of illness-related events (secondary HLH, or sHLH).
A powerful signaling cascade called a “cytokine storm” triggers HLH. One key component of this storm is a signaling molecule called interleukin-1 (IL-1).
Anankira, sold as Kineret by Sobi, is approved to treat active rheumatoid arthritis and neonatal-onset multisystem inflammatory disease (NOMID). The therapy works by blocking IL-1, reducing inflammation and the body’s immune responses.
Studies have shown that treatment with anakinra can improve survival and ameliorate symptoms in rheumatic diseases, such as systemic juvenile idiopathic arthritis (sJIA) and lupus, but its role in sHLH has not been widely explored.
To determine the benefits of anakinra in juvenile sHLH, researchers at the University of Alabama School of Medicine reviewed records (from January 2008 through December 2016) of children with sHLH who had been treated with the therapy. In total, the record of 44 patients (mean age of 10) were analyzed.
The most common underlying diseases in this sHLH group analyzed included systemic juvenile idiopathic arthritis (sJIA), lupus, mixed connective tissue disease, and malignancy/acute lymphoblastic leukemia. Sixteen (36%) sHLH patients did not have an identifiable rheumatic disease.
Results showed that overall mortality in this patient group was 27% (12 died), and their average hospital stay was 15 days. Five of the 12 deaths were attributed to shock, and six others to multi-organ system failure.
Treatment with anakinra was associated with improved overall survival, when compared to standard etoposide-based treatments.
Anakinra worked best in patients with underlying rheumatic conditions, such as sJIA and lupus. Patients with sJIA, in fact, had a 100% survival rate in this study.
Importantly, timing of anakinra treatment appeared to matter, with early treatment showing the strongest effect. “Earlier initiation of anakinra [within 5 days of hospitalization] was associated with further reduced mortality in all patients,” the researchers wrote.
The three children with cancer diagnoses had a 100% mortality rate, regardless of their remission status. This suggested that blocking IL-1 may prove ineffective when cancer is present.
Besides cancer, certain clinical findings appeared to influence the degree to which anakinra could provide benefit. For instance, a low blood platelet count (a condition called thrombocytopenia) was associated with a greater likelihood of death despite anakinra treatment.
Mutations in the STXBP2 gene were also linked to a higher risk for mortality, and a poorer response to anakinra treatment. Specifically, four out of five patients with STXBP2 mutations in the study died.
Ferritin, an iron storage molecule whose blood level is representative of the total iron stored in the body, was higher among patients who died. The amount by which ferritin levels dropped at 15 days of treatment was found to be significantly associated with survival.
Overall, the “findings suggest that anakinra appears to be effective in treating pediatric patients with non-malignancy-associated secondary HLH … especially when it is given early in the disease course and when administered to patients who have an underlying rheumatic disease,” the researchers wrote.
Of note, the study’s lead author, Randy Q. Cron, MD, PhD, is also the principal investigator of a Phase 1 clinical trial (NCT02780583) evaluating anakinra’s safety and tolerability as an adjunct (add-on) treatment for sHLH in children and adults. This study may still be recruiting patients at its sole University of Alabama site; contact information is available here.